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  • BIOLOGICALS
    • NOTE: This page is intended to be a quick reference for properties of commonly used biologicals. It is NOT a comprehensive review of each medication. Other drug interactions, side effects, precautions, and contraindications may exist for each drug. All information pertains to ADULT patients only.

TUMOR NECROSIS FACTOR INHIBITORS INTERLEUKIN RECEPTOR INHIBITORS
INTERLEUKIN INHIBITORS
INTRAVENOUS IMMUNOGLOBULIN (IVIG) B-CELL AGENTS
T-CELL AGENTS

OTHER RECENT STUDIES




Drug Dosage form Dosing Other Mechanism/FDA-approved indications Side effects
P = % of patients on placebo who experienced side effect
Contraindications/Precautions
Adalimumab

(Humira®)
Humira Pen
  • Comes in 20 mg and 40 mg dose
  • Comes in carton with 2 pens
  • There is a starter pack that contains four 40 mg pens (psoriasis) and one that contains six 40 mg pens (Crohn's)

Humira Syringe
  • Comes in 20 mg and 40 mg dose
  • Comes in carton with 2 syringes
Rheumatoid Arthritis, Psoriatic Arthritis, and Ankylosing Spondylitis
  • Dosing: 40 mg every other week
  • In rheumatoid arthritis, some patients not taking methotrexate may derive additional benefit from increasing the frequency to 40 mg once weekly

Crohn's disease
  • Day 1: 160 mg (given as four 40 mg injections in one day or as two 40 mg injections per day for two consecutive days)
  • Day 15: 80 mg
  • Day 29 and on: 40 mg every other week

Ulcerative colitis
  • Day 1: 160 mg (given as four 40 mg injections in one day or as two 40 mg injections per day for two consecutive days)
  • Day 15: 80 mg
  • Day 29 and on: 40 mg every other week

Plaque Psoriasis
  • Day 1: 80 mg
  • Day 8 and on: 40 mg every other week

Hidradenitis Suppurativa
  • Day 1: 160 mg (given as four 40 mg injections in one day or as two 40 mg injections per day for two consecutive days)
  • Day 15: 80 mg
  • Day 29 and on: 40 mg every week
  • Keep refrigerated
  • Humira may be stored at room temperature up to a maximum of 77°F (25°C) for a period of up to 14 days with protection from light
  • Humira is injected subcutaneously into the thigh or abdomen. Rotate injection sites.
  • May leave at room temperature for 15 - 30 minutes before injecting
  • Solution should be clear and colorless
Mechanism
  • Tumor Necrosis Factor inhibitor - Humira is a human monoclonal antibody (IgG) specific for human tumor necrosis factor alpha (TNF-alpha). Humira binds TNF-alpha and blocks its interaction with cell receptors. Humira may also lyse TNF expressing cells in the presence of complement.

Indications (FDA-approved)
  • Rheumatoid arthritis
  • Juvenile Idiopathic Arthritis
  • Psoriatic Arthritis
  • Ankylosing Spondylitis
  • Crohn’s Disease (adult and pediatric)
  • Ulcerative Colitis
  • Plaque Psoriasis
  • Hidradenitis Suppurativa
NOTE: only side effects that occurred at an incidence ≥ 2% more than placebo are listed. Data below is from rheumatoid arthritis trials.

  • Injection site reactions - 20% of patients; common reactions include redness, itching, bleeding, pain, and swelling.
  • Upper respiratory infection - 17%, P - 13%
  • Headache - 12%, P - 8%
  • Rash - 12%, P - 6%
  • Sinusitis - 11%, P - 9%
  • Accidental injury - 10%, P - 8%
  • Urinary tract infection - 8%, P - 5%
  • Abdominal pain - 7%, P - 4%
  • High cholesterol - 6%, P - 4%
  • Back pain - 6%, P - 4%
  • Increased alk phos - 5%, P - 3%
  • Hypertension - 5%, P - 3%
  • Tuberculosis (TB) - test patients for TB before use (≥ 5 mm induration should be considered positive). The American College of Rheumatology recommends treating latent TB for at least one month before starting a TNF inhibitor. Active TB should be treated completely before starting a TNF inhibitor. [2]
  • Serious infections - TNF inhibitors may increase the risk of serious infections including tuberculosis, invasive fungal infections, bacterial infections, viral infections, and others. In controlled trials, the rate of serious infections was 4.4 per 100 patient-years in 7723 Humira-treated patients versus a rate of 2.9 per 100 patient-years in 4598 control-treated patients.
  • Hepatitis B - patients infected with hepatitis B may have reactivation of disease while taking TNF inhibitors. Test patients before initiating therapy. Monitor infected patients closely.
  • Malignancies - TNF inhibitors may increase the risk for certain cancers, particularly lymphoma. Concomitant immunosuppressants may increase the risk.
  • Demyelinating diseases (e.g. multiple sclerosis) - TNF inhibitors may exacerbate demyelinating diseases. Use caution.
  • Blood dyscrasias - blood dyscrasias including aplastic anemia have been reported
  • Abatacept and anakinra - DO NOT COMBINE. Increases risk of serious infection.
  • Heart failure - TNF inhibitors may cause new onset heart failure or worsen existing heart failure. Use caution.
  • Drug-induced lupus - TNF inhibitors have been associated with drug-induced lupus in a small number of patients
  • Autoantibodies - in controlled trials, 12% of Humira-treated patients and 7% of placebo-treated patients developed positive ANA titers during treatment
  • Elevated liver enzymes - in controlled trials, ALT elevations ≥ 3 x ULN occurred in 3.5% of Humira-treated patients and 1.5% of control-treated patients. Concomitant methotrexate may increase the risk.
  • Humira antibodies - in adult trials, up to 8% of patients developed anti-Humira antibodies. It's unclear if antibody development is associated with reduced efficacy and/or hypersensitivity reactions.
  • Hypersensitivity reactions - hypersensitivity reactions including anaphylaxis have been reported
  • Vaccines - patients may receive non-live vaccines. Do not give live or attenuated vaccines (e.g. MMR, Varicella, BCG).
  • CYP enzyme activity - suppression of inflammatory mediators by TNF inhibitors may increase CYP enzyme activity and decrease blood levels of drugs metabolized by CYP enzymes
  • Liver disease - has not been studied
  • Kidney disease - has not been studied

Drug Dosage form Dosing Other Mechanism/FDA-approved indications Side effects
P = % of patients on placebo who experienced side effect
Contraindications/Precautions
Certolizumab
pegol

(Cimzia®)
Cimzia prefilled syringe
  • Comes in 200 mg dose
  • Comes in carton with 2 pens

Cimzia Vial
  • 200 mg/ml
  • Comes in kit with vial of powdered drug that must be reconstituted before injecting

Rheumatoid Arthritis, Psoriatic Arthritis, Ankylosing Spondylitis
  • Starting: 400 mg at Weeks 0, 2, and 4
  • Maintenance: 200 mg every other week or 400 mg every 4 weeks

Crohn's disease
  • Starting: 400 mg at Weeks 0, 2, and 4
  • Maintenance: 400 mg every 4 weeks
  • Keep refrigerated
  • Let medication warm to room temperature before injecting
  • Cimzia is injected subcutaneously into the thigh or abdomen. Rotate injection sites.
Mechanism
  • Tumor Necrosis Factor inhibitor - Cimzia is a recombinant, humanized antibody Fab' fragment with specificity for human tumor necrosis factor alpha (TNF-alpha). Cimzia binds TNF-alpha and neutralizes it.

Indications (FDA-approved)
  • Rheumatoid arthritis
  • Psoriatic Arthritis
  • Ankylosing Spondylitis
  • Crohn’s Disease (adult)
NOTE: only side effects that occurred at an incidence of ≥ 5% and more than placebo are listed. Data below is from Crohn's disease trials.

  • Upper respiratory infections - 20%, P - 13%
  • Urinary tract infections - 7%, P - 6%
  • Arthralgia - 6%, P - 4%
  • Tuberculosis (TB) - test patients for TB before use (≥ 5 mm induration should be considered positive). The American College of Rheumatology recommends treating latent TB for at least one month before starting a TNF inhibitor. Active TB should be treated completely before starting a TNF inhibitor. [2]
  • Serious infections - TNF inhibitors may increase the risk of serious infections including tuberculosis, invasive fungal infections, bacterial infections, viral infections, and others. In controlled trials, the rate of serious infections was 3% per year in Cimzia-treated patients and 1% per year for placebo-treated patients. Serious infections included bacterial and viral infections, pneumonia, and pyelonephritis.
  • Hepatitis B - patients infected with hepatitis B may have reactivation of disease while taking TNF inhibitors. Test patients before initiating therapy. Monitor infected patients closely.
  • Malignancies - TNF inhibitors may increase the risk for certain cancers, particularly lymphoma. Concomitant immunosuppressants may increase the risk.
  • Demyelinating diseases (e.g. multiple sclerosis) - TNF inhibitors may exacerbate demyelinating diseases. Use caution.
  • Blood dyscrasias - blood dyscrasias including aplastic anemia have been reported
  • Abatacept and anakinra - DO NOT COMBINE. Increases risk of serious infection.
  • Heart failure - TNF inhibitors may cause new onset heart failure or worsen existing heart failure. Use caution.
  • Drug-induced lupus - TNF inhibitors have been associated with drug-induced lupus in a small number of patients
  • Autoantibodies - in controlled trials, 4% of Cimzia-treated patients and 2% of placebo-treated patients developed positive ANA titers during treatment
  • Cimzia antibodies - in long-term Crohn's disease trials, up to 23% of patients developed anti-Cimzia antibodies. In RA trials, 7% of patients developed anti-Cimzia antibodies. In the RA trials, antibody development was associated with lower drug plasma concentrations and reduced efficacy.
  • Hypersensitivity reactions - hypersensitivity reactions including anaphylaxis have been reported
  • Vaccines - patients may receive non-live vaccines. Do not give live or attenuated vaccines (e.g. MMR, Varicella, BCG).
  • CYP enzyme activity - suppression of inflammatory mediators by TNF inhibitors may increase CYP enzyme activity and decrease blood levels of drugs metabolized by CYP enzymes
  • Coagulation studies - Cimzia may cause an erroneously prolonged activated Partial Thromboplastin Time (aPTT)
  • Liver disease - has not been studied
  • Kidney disease - has not been studied

Drug Dosage form Dosing Other Mechanism/FDA-approved indications Side effects
P = % of patients on placebo who experienced side effect
Contraindications/Precautions
Etanercept

(Enbrel®)
(Erelzi®)
Enbrel®   
Enbrel prefilled syringe
  • Comes in 25 mg and 50 mg doses
  • Comes in carton with 4 pens

Enbrel SureClick autoinjector
  • Comes in 50 mg dose
  • Comes in carton with 4 autoinjectors

Enbrel Vial
  • Comes in 25 mg multi-use vial
  • Comes in carton with 4 vials
  • Drug must be reconstituted

Erelzi®   
  • Erelzi is a biosimilar to Enbrel
  • Erelzi is etanercept-szzs

Erelzi prefilled syringe
  • Comes in 25 mg and 50 mg doses
  • Comes in carton with 1 or 4 pens

Erelzi Sensoready Pen
  • Comes in 50 mg dose
  • Comes in carton with 1 or 4 pens
Rheumatoid Arthritis, Psoriatic Arthritis, Ankylosing Spondylitis
  • Dosing: 50 mg once weekly

Plaque Psoriasis
  • Starting: 50 mg twice weekly for 3 months
  • Maintenance: 50 mg once weekly
  • Starting doses of 25 - 50 mg once weekly have also been shown to be effective
General
  • Keep refrigerated
  • Let Enbrel/Erelzi warm to room temperature for 15 - 30 minutes before injecting
  • Inject subcutaneously in the thigh, abdomen, or outer upper arms. Rotate injection sites.
  • See medication guide and instructions for use for more information on storage and proper injection technique
Mechanism
  • Tumor Necrosis Factor inhibitor - Enbrel is a dimeric fusion protein consisting of the extracellular ligand-binding portion of the human 75 kilodalton (p75) tumor necrosis factor receptor (TNFR) linked to the Fc portion of human IgG1. Enbrel inhibits binding of TNF-alpha and TNF-beta to cell surface TNFRs.

Indications (FDA-approved)
  • Rheumatoid arthritis
  • Polyarticular Juvenile Idiopathic Arthritis in patients ≥ 2 years old
  • Psoriatic Arthritis
  • Ankylosing Spondylitis
  • Plaque Psoriasis in patients ≥ 4 years old
NOTE: only side effects that occurred at an incidence of ≥ 2% more than placebo are listed. Data below is from RA trials.

  • Injection site reactions - up to 37% of patients; reactions include redness, itching, pain, swelling, bleeding, and bruising; average duration of reactions is 3 - 5 days; reactions typically occurred in the first month and then decreased in frequency
  • Upper respiratory infections - 38%, P - 30%
  • Non-upper respiratory infections - 21%, P - 15%
  • Fever - 3%, P - 0%
  • Tuberculosis (TB) - test patients for TB before use (≥ 5 mm induration should be considered positive). The American College of Rheumatology recommends treating latent TB for at least one month before starting a TNF inhibitor. Active TB should be treated completely before starting a TNF inhibitor. [2]
  • Serious infections - TNF inhibitors may increase the risk of serious infections including tuberculosis, invasive fungal infections, bacterial infections, viral infections, and others. In controlled trials, rates of serious infections were 1.4% in Enbrel-treated patients and 0.8% in placebo-treated patients. In rheumatological trials, serious infections included pneumonia, cellulitis, septic arthritis, bronchitis, gastroenteritis, pyelonephritis, sepsis, abscess and osteomyelitis.
  • Hepatitis B - patients infected with hepatitis B may have reactivation of disease while taking TNF inhibitors. Test patients before initiating therapy. Monitor infected patients closely.
  • Malignancies - TNF inhibitors may increase the risk for certain cancers, particularly lymphoma. Concomitant immunosuppressants may increase the risk.
  • Demyelinating diseases (e.g. multiple sclerosis) - TNF inhibitors may exacerbate demyelinating diseases. Use caution.
  • Blood dyscrasias - blood dyscrasias including aplastic anemia have been reported
  • Abatacept and anakinra - DO NOT COMBINE. Increases risk of serious infection.
  • Cyclophosphamide - DO NOT COMBINE. May increase risk of malignancy.
  • Sulfasalazine - combination may decrease neutrophil count
  • Heart failure - TNF inhibitors may cause new onset heart failure or worsen existing heart failure. Use caution.
  • Drug-induced lupus - TNF inhibitors have been associated with drug-induced lupus in a small number of patients
  • Autoantibodies - in controlled trials, 11% of Enbrel-treated patients and 5% of placebo-treated patients developed positive ANA titers during treatment
  • Wegener's granulomatosis - DO NOT USE. May increase risk of malignancy.
  • Alcoholic hepatitis - Use caution. May increase mortality.
  • Enbrel antibodies - in trials, anti-Enbrel antibodies were detected in up to 9% of patients. Antibody development did not appear to affect drug efficacy.
  • Hypersensitivity reactions - hypersensitivity reactions including anaphylaxis have been reported
  • Vaccines - patients may receive non-live vaccines. Do not give live or attenuated vaccines (e.g. MMR, Varicella, BCG).
  • CYP enzyme activity - suppression of inflammatory mediators by TNF inhibitors may increase CYP enzyme activity and decrease blood levels of drugs metabolized by CYP enzymes
  • Liver disease - has not been studied
  • Kidney disease - has not been studied

Drug Dosage form Dosing Other Mechanism/FDA-approved indications Side effects
P = % of patients on placebo who experienced side effect
Contraindications/Precautions
Golimumab

(Simponi®)
(Simponi Aria®)
Simponi prefilled syringe
  • Comes 50 mg and 100 mg doses

Simponi SmartJect autoinjector
  • Comes 50 mg and 100 mg doses

Simponi Aria Vial
  • 50 mg/4 ml single-use vial
Simponi syringe and autoinjector

Rheumatoid Arthritis, Psoriatic Arthritis, Ankylosing Spondylitis
  • Dosing: 50 mg once a month
  • For patients with rheumatoid arthritis, Simponi should be given with methotrexate

Ulcerative colitis
  • Starting: 200 mg at Week 0, followed by 100 mg at Week 2
  • Maintenance: 100 mg every 4 weeks

Simponi Aria intravenous infusion

Rheumatoid Arthritis
  • Starting: 2 mg/kg at Week 0 and 4
  • Maintenance: 2 mg/kg every 8 weeks
  • Simponi should be given with methotrexate
Syringe and autoinjector
  • Keep refrigerated
  • Let Simponi warm to room temperature for 30 minutes before injecting
  • Inject subcutaneously in the thigh, abdomen, or outer upper arms. Rotate injection sites.
  • Simponi should be clear to slightly opalescent and colorless to light yellow

Simponi Aria
  • Keep refrigerated
  • Must be infused intravenously over 30 minutes
  • Solution should be colorless to light yellow. The solution may develop a few fine translucent particles.
Mechanism
  • Tumor Necrosis Factor inhibitor - Simponi is is a human IgG1қ monoclonal antibody specific for human tumor necrosis factor alpha (TNF-alpha). Simponi binds TNF-alpha and prevents it from binding with TNF-alpha receptors.

Indications (FDA-approved)
Simponi
  • Rheumatoid arthritis (in combination with methotrexate)
  • Psoriatic Arthritis
  • Ankylosing Spondylitis
  • Ulcerative colitis

Simponi Aria
  • Rheumatoid arthritis in combination with methotrexate
NOTE: only side effects that occurred at an incidence of ≥ 2% more than placebo are listed. Data below is from trials where Simponi was given in combination with other DMARDs.

  • Upper respiratory infections - 16%, P - 13%
  • Viral infections (e.g. influenza and herpes) - 5%, P - 3%
  • Injection site reactions - up to 6% of patients; most reactions were mild; most frequent reaction was redness
  • Infusion reactions (Simponi Aria) - 1.1% of patients; most common reaction was rash
  • Tuberculosis (TB) - test patients for TB before use (≥ 5 mm induration should be considered positive). The American College of Rheumatology recommends treating latent TB for at least one month before starting a TNF inhibitor. Active TB should be treated completely before starting a TNF inhibitor. [2]
  • Serious infections - TNF inhibitors may increase the risk of serious infections including tuberculosis, invasive fungal infections, bacterial infections, viral infections, and others. In controlled trials, the incidence of serious infections was 5.7 per 100 patient-years in Simponi-treated patients and 4.2 per 100 patient-years in placebo-treated patients.
  • Hepatitis B - patients infected with hepatitis B may have reactivation of disease while taking TNF inhibitors. Test patients before initiating therapy. Monitor infected patients closely.
  • Malignancies - TNF inhibitors may increase the risk for certain cancers, particularly lymphoma. Concomitant immunosuppressants may increase the risk.
  • Demyelinating diseases (e.g. multiple sclerosis) - TNF inhibitors may exacerbate demyelinating diseases. Use caution.
  • Blood dyscrasias - blood dyscrasias including aplastic anemia have been reported
  • Abatacept and anakinra - DO NOT COMBINE. Increases risk of serious infection.
  • Heart failure - TNF inhibitors may cause new onset heart failure or worsen existing heart failure. Use caution.
  • Drug-induced lupus - TNF inhibitors have been associated with drug-induced lupus in a small number of patients
  • Autoantibodies - in controlled trials, 4% of Simponi-treated patients and 2.6% of placebo-treated patients developed positive ANA titers during treatment
  • Elevated liver enzymes - in controlled trials, ALT elevations ≥ 3 x ULN occurred in 2% of control-treated patients and 2% of Simponi-treated patients. Concomitant methotrexate may increase the risk.
  • Simponi antibodies - in trials, anti-Simponi antibodies were detected in up to 7% of patients. It's unclear if antibody development is associated with reduced efficacy.
  • Hypersensitivity reactions - hypersensitivity reactions including anaphylaxis have been reported
  • Vaccines - patients may receive non-live vaccines. Do not give live or attenuated vaccines (e.g. MMR, Varicella, BCG).
  • CYP enzyme activity - suppression of inflammatory mediators by TNF inhibitors may increase CYP enzyme activity and decrease blood levels of drugs metabolized by CYP enzymes
  • Liver disease - has not been studied
  • Kidney disease - has not been studied

Drug Dosage form Dosing Other Mechanism/FDA-approved indications Side effects
P = % of patients on placebo who experienced side effect
Contraindications/Precautions
Infliximab

(Remicade®)
(Inflectra®)
Remicade Vial
  • 100 mg single dose vial

Inflectra Vial
  • 100 mg single dose vial
  • Inflectra is a biosimilar to Remicade
  • Inflectra is infliximab-dyyb
Crohn's disease
  • Starting: 5 mg/kg at Weeks 0, 2, and 6
  • Maintenance: 5 mg/kg every 8 weeks
  • May increase to 10 mg/kg in patients who respond and then lose their response

Ulcerative colitis
  • Starting: 5 mg/kg at Weeks 0, 2, and 6
  • Maintenance: 5 mg/kg every 8 weeks

Rheumatoid arthritis
  • Starting: 3 mg/kg at Weeks 0, 2, and 6
  • Maintenance: 3 mg/kg every 8 weeks
  • Should be given with methotrexate
  • May increase dose to 10 mg/kg or shorten dosing interval to 4 weeks in patients with partial response

Ankylosing spondylitis
  • Starting: 5 mg/kg at Weeks 0, 2, and 6
  • Maintenance: 5 mg/kg every 6 weeks

Psoriatic arthritis
  • Starting: 5 mg/kg at Weeks 0, 2, and 6
  • Maintenance: 5 mg/kg every 8 weeks

Plaque Psoriasis
  • Starting: 5 mg/kg at Weeks 0, 2, and 6
  • Maintenance: 5 mg/kg every 8 weeks
  • Prior to infusion, may premedicate with antihistamine, acetaminophen, and/or corticosteroids
  • Infuse over a period of not less than 2 hours
  • Keep vials refrigerated
  • Unopened vials may also be stored at temperatures up to a maximum of 30°C (86°F) for a single period of up to 6 months
  • Upon removal from refrigerated storage, Remicade cannot be returned to refrigerated storage
Mechanism
  • Tumor Necrosis Factor inhibitor - Remicade is a chimeric IgG1κ monoclonal antibody (composed of human constant and murine variable regions) specific for human tumor necrosis factor-alpha (TNF-alpha). Remicade binds TNF-alpha and prevents it from binding with TNF-alpha receptors.

Indications (FDA-approved)
  • Crohn's disease (adult and pediatric)
  • Rheumatoid arthritis (in combination with methotrexate)
  • Psoriatic Arthritis
  • Ankylosing Spondylitis
  • Ulcerative colitis (adult and pediatric)
  • Plaque Psoriasis
NOTE: only side effects that occurred at an incidence of ≥ 2% more than placebo are listed. Data below is from RA trials.

  • Infusion reactions - up to 18% of patients; serious reactions are rare
  • Upper respiratory tract infection - 32%, P - 25%
  • Headache - 18%, P - 14%
  • Sinusitis - 14%, P - 8%
  • Pharyngitis - 12%, P - 8%
  • Coughing - 12%, P - 8%
  • Abdominal pain - 12%, P - 8%
  • Rash - 10%, P - 5%
  • Dyspepsia - 10%, P - 7%
  • Fatigue - 9%, P - 7%
  • Urinary tract infection - 8%, P - 6%
  • Hypertension - 7%, P - 5%
  • Fever - 7%, P - 4%
  • Itching - 7%, P - 2%
  • Yeast infection - 5%, P - 3%
  • Tuberculosis (TB) - test patients for TB before use (≥ 5 mm induration should be considered positive). The American College of Rheumatology recommends treating latent TB for at least one month before starting a TNF inhibitor. Active TB should be treated completely before starting a TNF inhibitor. [2]
  • Serious infections - TNF inhibitors may increase the risk of serious infections including tuberculosis, invasive fungal infections, bacterial infections, viral infections, and others. In RA patients treated for 1 year, 5.3% of Remicade-treated patients developed serious infections as compared to 3.4% of placebo-treated patients.
  • Elevated liver enzymes - in controlled trials, ALT elevations between 1 - 3 X ULN occurred in up to 51% of Remicade-treated patients. ALT elevations ≥ 3 X ULN occurred in up to 10% of Remicade-treated patients. Mild-to-moderate elevations typically decreased or resolved with either continuation or discontinuation of Remicade, or modification of concomitant medications. Discontinue Remicade if LFTs reach ≥ 5 X ULN.
  • Hepatitis B - patients infected with hepatitis B may have reactivation of disease while taking TNF inhibitors. Test patients before initiating therapy. Monitor infected patients closely.
  • Malignancies - TNF inhibitors may increase the risk for certain cancers, particularly lymphoma. Concomitant immunosuppressants may increase the risk.
  • Demyelinating diseases (e.g. multiple sclerosis) - TNF inhibitors may exacerbate demyelinating diseases. Use caution.
  • Heart failure - Remicade may cause new-onset heart failure or worsen existing heart failure. Remicade at doses > 5 mg/kg should not be given to patients with moderate to severe (NYHA III and IV) heart failure.
  • Blood dyscrasias - blood dyscrasias including aplastic anemia have been reported
  • Abatacept and anakinra - DO NOT COMBINE. Increases risk of serious infection.
  • Tocilizumab - DO NOT COMBINE. Increases risk of serious infection.
  • Drug-induced lupus - TNF inhibitors have been associated with drug-induced lupus in a small number of patients
  • Autoantibodies - in controlled trials, 50% of Remicade-treated patients and 20% of placebo-treated patients developed positive ANA titers during treatment. Anti-dsDNA antibodies developed in 20% of Remicade-treated patients compared to 0% of placebo-treated patients.
  • Remicade antibodies - in trials, anti-Remicade antibodies were detected in up to 51% of patients. In some studies, antibody development was associated with reduced efficacy and an increased rate of infusion reactions.
  • Hypersensitivity reactions - hypersensitivity reactions including anaphylaxis have been reported
  • Vaccines - patients may receive non-live vaccines. Do not give live or attenuated vaccines (e.g. MMR, Varicella, BCG).
  • CYP enzyme activity - suppression of inflammatory mediators by TNF inhibitors may increase CYP enzyme activity and decrease blood levels of drugs metabolized by CYP enzymes
  • Liver disease - has not been studied
  • Kidney disease - has not been studied




Drug Dosage form Dosing Lab monitoring Other Mechanism/FDA-approved indications Side effects
P = % of patients on placebo who experienced side effect
Contraindications/Precautions
Anakinra

(Kineret®)
Prefilled syringe
  • Comes in 100 mg dose
  • Comes in pack of 28 syringes
Rheumatoid arthritis
  • Dosing: 100 mg once daily
  • Dose should be given at the same time every day
Neutropenia
  • Check neutrophil count before starting therapy
  • Check neutrophil count monthly for 3 months when starting therapy, and thereafter quarterly for a period up to 1 year
  • Keep refrigerated
  • Allow syringe to warm to room temperature for 30 minutes before injecting
  • Solution should be colorless. There may be trace amounts of small, translucent-to-white amorphous particles of protein in the solution.
  • Inject subcutaneously in the thigh, abdomen, or outer upper arms. Rotate injection sites.
Mechanism
  • Interleukin-1-receptor inhibitor - Kineret is a recombinant, nonglycosylated form of the human interleukin-1 receptor antagonist (IL-1Ra). Kineret binds to IL-1 receptors and blocks the activity of IL-1 alpha and beta.

Indications (FDA-approved)
  • Rheumatoid arthritis
  • Cryopyrin-associated periodic syndromes
NOTE: Only side effects that occurred at an incidence of ≥ 2% more than placebo are listed.

  • Injection site reactions - up to 71% of patients; common reactions include erythema, ecchymosis, inflammation, and pain; reactions typically last 14 - 28 days; reactions typically occur within first 4 weeks of therapy
  • Headache - 12%, P - 9%
  • Diarrhea - 7%, P - 5%
  • Tuberculosis (TB) - test patients for TB before use (≥ 5 mm induration should be considered positive). The American College of Rheumatology recommends treating latent TB for at least one month before starting anakinra. Active TB should be treated completely before starting anakinra. [2]
  • Serious infections - Kineret may increase the risk of serious infections including tuberculosis, invasive fungal infections, bacterial infections, viral infections, and others. In trials lasting 1 year, the incidence of serious infections in Kineret-treated patients was 3% compared to 2% in placebo-treated patients. Patients with asthma may be at higher risk.
  • TNF inhibitors - DO NOT COMBINE. May increase risk of serious infection.
  • Neutropenia - in trials, 8% of Kineret-treated patients had a decrease in WBCs of at least one WHO toxicity grade compared to 2% of placebo-treated patients. See Lab monitoring for further recommendations.
  • Eosinophilia - in trials, 9% of Kineret-treated patients had an increase in eosinophils of at least one WHO toxicity grade compared to 3% of placebo-treated patients.
  • Hypersensitivity reactions - hypersensitivity reactions including anaphylaxis have been reported
  • Malignancies - may increase the risk for malignancies
  • Vaccines - patients may receive non-live vaccines. Do not give live or attenuated vaccines (e.g. MMR, Varicella, BCG).
  • Kineret antibodies - in trials, anti-Kineret antibodies were detected in up to 49% of patients. It's unclear if antibody development is associated with reduced efficacy.
  • CYP enzyme activity - suppression of inflammatory mediators by Kineret may increase CYP enzyme activity and decrease blood levels of drugs metabolized by CYP enzymes
  • Liver disease - has not been studied
  • Kidney disease
    • CrCl < 30 ml/min: consider dosing every other day

Drug Dosage form Dosing Lab monitoring Other Mechanism/FDA-approved indications Side effects
P = % of patients on placebo who experienced side effect
Contraindications/Precautions
Tocilizumab

(Actemra®)
Prefilled syringe
  • Comes in 162 mg dose

Single-use vial
  • 80 mg
  • 200 mg
  • 400 mg
  • Comes in 20 mg/ml concentration
Rheumatoid arthritis
  • Prefilled syringe (subcutaneous)
    • Weight < 220 pounds (100 kg): 162 mg every other week. May increase to every week based on response.
    • Weight ≥ 220 pounds (100 kg): 162 mg every week

  • Infusion
    • Dosing: 4 mg/kg every 4 weeks
    • May increase to 8 mg/kg every 4 weeks based on response
    • Doses exceeding 800 mg per infusion are not recommended

Giant Cell Arteritis
  • 162 mg SQ once weekly in combination with a tapering course of glucocorticoids

Polyarticular Juvenile Idiopathic Arthritis
  • Weight < 66 lbs (30 kg): 10 mg/kg every 4 weeks by IV infusion
  • Weight ≥ 66 lbs (30 kg): 8 mg/kg every 4 weeks by IV infusion
  • May be used alone or in combination with methotrexate

Systemic Juvenile Idiopathic Arthritis
  • Weight < 66 lbs (30 kg): 12 mg/kg every 2 weeks by IV infusion
  • Weight ≥ 66 lbs (30 kg): 8 mg/kg every 2 weeks by IV infusion
  • May be used alone or in combination with methotrexate
Neutropenia
  • Do not initiate in patients with ANC < 2000 cells/mm³
  • Check neutrophil count 4 - 8 weeks after starting therapy and every 3 months thereafter

Thrombocytopenia
  • Do not initiate in patients with platelet count < 100,000/mm³
  • Check platelet count 4 - 8 weeks after starting therapy and every 3 months thereafter

Elevated LFTs
  • Do not initiate in patients with AST or ALT > 1.5 X ULN
  • Check LFTs 4 - 8 weeks after starting therapy and every 3 months thereafter

Increased cholesterol
  • Check lipid parameters 4 - 8 weeks after starting therapy and every 24 weeks thereafter


See the Actemra PI sec 2.7 for recommendations on adjusting dosage based on lab results
Prefilled syringe
  • Keep refrigerated
  • Solution should be clear and colorless to pale yellow
  • Inject subcutaneously in the thigh, abdomen, or outer upper arms. Rotate injection sites.

Vials
  • Infuse over 60 minutes
Mechanism
  • Interleukin-6-receptor inhibitor - tocilizumab is a recombinant humanized anti-human interleukin 6 (IL-6) receptor monoclonal antibody of the immunoglobulin IgG1κ (gamma 1, kappa) subclass. Tocilizumab binds IL-6 receptors and inhibits the action of IL-6.

Indications (FDA-approved)
  • Rheumatoid arthritis
  • Giant Cell Arteritis
  • Polyarticular juvenile idiopathic arthritis
  • Systemic juvenile idiopathic arthritis
NOTE: Only side effects that occurred at an incidence of ≥ 2% more than placebo are listed.

  • Nasopharyngitis - 7%, P - 4%
  • Headache - 7%, P - 3%
  • Hypertension - 6%, P - 3%
  • ALT increase - 6%, P - 1%
  • Injection site reactions - up to 10% of patients; common reactions include erythema, pruritus, pain and hematoma
  • Infusion reactions - up to 8% of patients; common reactions include headache, hypertension, and skin reactions
  • Tuberculosis (TB) - test patients for TB before use (≥ 5 mm induration should be considered positive). The American College of Rheumatology recommends treating latent TB for at least one month before starting tocilizumab. Active TB should be treated completely before starting tocilizumab. [2]
  • Serious infections - Actemra may increase the risk of serious infections including tuberculosis, invasive fungal infections, bacterial infections, viral infections, and others. In RA patients treated for 24 weeks, 3.6 serious infections per 100 patient-years occurred in Actemra-treated patients compared to 1.5 serious infections per 100 patient-years in placebo-treated patients.
  • Hepatitis B - patients infected with hepatitis B may have reactivation of disease while taking Actemra. Test patients before initiating therapy. Monitor infected patients closely.
  • Herpes zoster - reactivation of herpes zoster has occurred in patients using Actemra
  • Gastrointestinal perforations - in trials, a small number of patients developed gastrointestinal perforations while using Actemra. Most cases were reported as complications of diverticulitis.
  • Neutropenia - seen in up to 3.4% of patients. Do not initiate Actemra in patients with ANC < 2000 cells/mm³. See Lab monitoring for further recommendations.
  • Thrombocytopenia - seen in up to 1.7% of patients. Do not initiate Actemra in patients with platelet count < 100,000/mm³. See Lab monitoring for further recommendations.
  • Elevated liver enzymes - seen in up to 48% of patients. Do not initiate Actemra in patients with AST or ALT > 1.5 X ULN. See Lab monitoring for further recommendations.
  • Elevated lipid parameters - elevated lipid parameters are seen in a significant number of patients. See Lab monitoring for further recommendations.
  • Hypersensitivity reactions - hypersensitivity reactions including anaphylaxis have been reported
  • Malignancies - may increase the risk for malignancies
  • Demyelinating diseases (e.g. multiple sclerosis) - may exacerbate demyelinating diseases. Use caution.
  • Actemra antibodies - in trials, anti-Actemra antibodies were detected in up to 2% of patients. In some patients, antibody development was associated with the development of hypersensitivity reactions. It's unclear if antibody development is associated with reduced efficacy.
  • Vaccines - patients may receive non-live vaccines. Do not give live or attenuated vaccines (e.g. MMR, Varicella, BCG).
  • CYP enzyme activity - suppression of inflammatory mediators by Actemra may increase CYP enzyme activity and decrease blood levels of drugs metabolized by CYP enzymes
  • Liver disease - DO NOT USE in active liver disease
  • Kidney disease - has not been studied




Drug Dosage form Dosing Lab monitoring Other Mechanism/FDA-approved indications Side effects
P = % of patients on placebo who experienced side effect
Contraindications/Precautions
Ustekinumab

(Stelara®)
Prefilled syringe
  • 45 mg
  • 90 mg

Single-use vial
  • 45 mg

Vial for intravenous use
  • 130 mg/26 ml (5 mg/ml)
Psoriasis
    • Weight ≤ 220 lbs (100 kg): 45 mg SQ initially and 4 weeks later, followed by 45 mg every 12 weeks
    • Weight > 220 lbs (100 kg): 90 mg SQ initially and 4 weeks later, followed by 90 mg every 12 weeks

Psoriatic arthritis
    • Dosing: 45 mg SQ initially and 4 weeks later, followed by 45 mg every 12 weeks
    • Patients weighing > 220 lbs (100 kg) with moderate-to-severe plaque psoriasis: 90 mg SQ initially and 4 weeks later, followed by 90 mg every 12 weeks

Crohn's disease
    • Initial: single intravenous dose based on the table below
Weight Dose # of vials (130 mg/26ml)
≤ 55 kg 260 mg 2
55 - 85 kg 390 mg 3
> 85 kg 520 mg 4

    • Maintenance: 90 mg SQ every 8 weeks starting 8 weeks after the initial IV dose
  • None recommended by manufacturer
Prefilled syringe
  • Keep refrigerated
  • Inject subcutaneously in the thigh, gluteal regions, abdomen, or upper arms. Rotate injection sites.

Infusion
  • Infuse over at least one hour
Mechanism
  • Interleukin inhibitor - ustekinumab is a human IgG1қ monoclonal antibody that binds with specificity to the p40 protein subunit used by both the IL-12 and IL-23 cytokines. IL-12 and IL-23 are naturally occurring cytokines that are involved in inflammatory and immune responses, such as natural killer cell activation and CD4+ T-cell differentiation and activation. Ustekinumab has been shown to disrupt IL-12 and IL-23 mediated signaling and cytokine cascades by disrupting the interaction of these cytokines with a shared cell-surface receptor chain, IL-12Rβ1. The cytokines IL-12 and IL-23 have been implicated as important contributors to the chronic inflammation that is a hallmark of Crohn's disease

Indications (FDA-approved)
  • Crohn's disease - moderate-to-severe disease in patients who have failed treatment with immunomodulators, corticosteroids, or tumor necrosis factor inhibitors
  • Psoriasis - moderate-to-severe disease
  • Psoriatic arthritis - may be used alone or with methotrexate
NOTE: Data is from 44-week study in Crohn's disease. Only side effects that occurred at an incidence of ≥ 3% overall and greater than placebo are listed.

  • Nasopharyngitis - 11%, P - 8%
  • Injection site erythema - 5%, P - 0%
  • Vulvovaginal candidiasis - 5%, P - 1%
  • Bronchitis - 5%, P - 3%
  • Pruritus - 4%, P - 2%
  • Urinary tract infection - 4%, P - 2%
  • Sinusitis - 3%, P - 2%
  • BCG vaccination - DO NOT GIVE during treatment or within one year following the end of treatment. Do not give ustekinumab to patients who have received the BCG vaccine within the previous year.
  • Live vaccines - DO NOT GIVE live vaccines to patients receiving ustekinumab. Use caution when giving live vaccines to household members. Common live vaccines include MMR, shingles (zoster), varicella (chickenpox), rotavirus, oral polio, influenza nasal vaccine (Flumist), Yellow fever, and adenovirus.
  • Non-live vaccines - non-live vaccines may not elicit the appropriate immune response in patients receiving ustekinumab
  • Allergen immunotherapy - allergen immunotherapy may not elicit the appropriate immune response in patients receiving ustekinumab
  • Serious infections - ustekinumab may increase the risk of serious infections. In psoriasis trials lasting 13 weeks, serious infections were reported in 0.3% of ustekinumab-treated patients and 0.4% of placebo-treated patients.
  • Theoretical risk for particular infections - patients with genetic deficiencies of IL-12/IL-23 are vulnerable to disseminated infections from mycobacteria, salmonella, and the BCG vaccine. It is unknown if ustekinumab increases the risk of these infections.
  • Tuberculosis (TB) - test all patients for TB before use. Do not treat patients with active TB. Start treatment for latent TB before initiating ustekinumab. Monitor for signs of active TB during treatment.
  • Malignancies - ustekinumab may increase the risk for malignancies. In Crohn's disease trials lasting up to one year, malignancies other than nonmelanoma skin cancers were reported in 0.2% of ustekinumab-treated patients and 0% of placebo-treated patients.
  • Nonmelanoma skin cancers - ustekinumab may particularly increase the risk of nonmelanoma skin cancer. In psoriasis trials lasting a median of 3.2 years, nonmelanoma skin cancers were reported in 1.5% of ustekinumab-treated patients. Rapid appearance of multiple cutaneous squamous cell carcinomas have been reported in patients receiving ustekinumab.
  • Hypersensitivity reactions - hypersensitivity reactions including anaphylaxis have been reported in a small number of patients. In Crohn's disease trials, 0.1% of patients receiving SQ ustekinumab and 0.08% of patients receiving IV ustekinumab reported hypersensitivity reactions.
  • Reversible Posterior Leukoencephalopathy Syndrome (RPLS) - in trials, one case of RPLS occurred in a patient receiving ustekinumab. Symptoms of RPLS include headache, seizures, confusion and visual disturbances.
  • Ustekinumab antibodies - in trials, anti-ustekinumab antibodies were detected in 6% of psoriasis patients and less than 3% of Crohn's patients. Antibody development was not associated with the development of hypersensitivity reactions. It's unknown if antibody development is associated with reduced efficacy.
  • CYP enzyme activity - suppression of inflammatory mediators by ustekinumab may increase CYP enzyme activity and decrease blood levels of drugs metabolized by CYP enzymes
  • Liver disease - has not been studied
  • Kidney disease - has not been studied




Drug Dosage form Dosing Other Mechanism/FDA-approved indications Side effects
P = % of patients on placebo who experienced side effect
Contraindications/Precautions
Belimumab

(Benlysta®)
Single-use vials
  • Comes in 120 mg and 400 mg vials
Systemic Lupus Erythematosus
  • Starting: 10 mg/kg at 2-week intervals for 3 doses
  • Maintenance: 10 mg/kg every 4 weeks
  • Benlysta is given by IV infusion over a period of 1 hour
  • Premedication (e.g. antihistamines, Tylenol, steroids) is recommended to prevent infusion reactions
Mechanism
  • B-cell depleting agent - B-lymphocyte stimulator (BLyS) is a growth factor required for B-cell survival, maturation, and activation. Belimumab is a fully humanized IgG monoclonal antibody that binds and inactivates soluble BLyS. By inactivating BLyS, belimumab inhibits the survival of B cells, including autoreactive B cells, and reduces the differentiation of B cells into immunoglobulin-producing plasma cells.

Indications (FDA-approved)
  • Systemic Lupus Erythematosus
NOTE: Only side effects that occurred at incidence of ≥ 3% overall, and ≥ 2% more than placebo are listed

  • Infusion reactions - up to 17% of patients; common reactions include headache, nausea, and skin reactions
  • Nausea - 15%, P - 12%
  • Diarrhea - 12%, P - 9%
  • Fever - 10%, P - 8%
  • Nasopharyngitis - 9%, P - 7%
  • Bronchitis - 9%, P - 5%
  • Insomnia - 7%, P - 5%
  • Pain in extremity - 6%, P - 4%
  • Pharyngitis - 5%, P - 3%
  • Leukopenia - 4%, P - 2%
  • Gastroenteritis - 3%, P - 1%
  • Serious infections - Benlysta may increase the risk of serious infections. In trials, serious infections occurred in 6% of Benlysta-treated patients and 5.2% of placebo-treated patients. The most frequent serious infections included pneumonia, urinary tract infection, cellulitis, and bronchitis.
  • Progressive Multifocal Leukoencephalopathy (PML) - JC virus infections resulting in PML and death have occurred. Consider PML diagnosis in patients with new-onset or deteriorating neurological signs and symptoms.
  • Hypersensitivity reactions - hypersensitivity reactions including anaphylaxis and death have occurred. In trials, hypersensitivity reactions on the same day of infusion were reported in 13% of Benlysta-treated patients and 11% of placebo-treated patients. Reactions included rash, itching, angioedema, hypotension, and dyspnea.
  • Depression - in trials, psychiatric complaints including depression, anxiety, and insomnia occurred in 16% of Benlysta-treated patients and 12% of placebo-treated patients
  • Malignancy - may increase the risk of malignancies
  • Immunizations - live vaccines should not be given 30 days before or concurrently with Benlysta
  • Cyclophosphamide - DO NOT COMBINE. Benlysta has not been studied in patients receiving intravenous cyclophosphamide.
  • Biologicals - DO NOT COMBINE. Benlysta has not been studied in patients receiving other biologicals.
  • Benlysta antibodies - anti-Benlysta antibodies were detected in up to 4.8% of patients. It's unclear if antibody development is associated with reduced efficacy and/or an increase in hypersensitivity reactions.
  • Lupus nephritis - patients with severe lupus nephritis were excluded from trials. The effects of Benlysta in these patients are unknown.
  • CNS lupus - patients with CNS lupus were excluded from trials. The effects of Benlysta in these patients are unknown.
  • Kidney disease - dosage adjustment is not recommended
  • Liver disease - has not been studied

Drug Dosage form Dosing Lab monitoring Other Mechanism/FDA-approved indications Side effects
P = % of patients on placebo who experienced side effect
Contraindications/Precautions
Rituximab

(Rituxan®)
Single-use vials
  • Comes in 100 mg and 500 mg vials
  • Drug concentration is 10 mg/ml
Rheumatoid arthritis
  • Dosing: one course of Rituxan is two 1000 mg doses given 2 weeks apart
  • One course may be given every 24 weeks based on clinical response
  • Courses should not be given sooner than every 16 weeks
  • Rituxan should be given with methotrexate

Immune thrombocytopenia (off-label)
  • 100 mg/week for 4 weeks OR 375 mg/m2/week for 4 weeks
  • Dosing is the same in children and adults
  • Response is highly variable. Only recommended as third- or fourth-line agent.
  • See immune thrombocytopenia for more
NOTE: Recommendations are for treating RA patients only. Recommendations in patients with malignancies differ.

Blood dyscrasias
  • In patients with RA, check CBC with platelets at 2 - 4 month intervals during Rituxan therapy
  • Rituxan is given as an IV infusion
  • Glucocorticoids administered as methylprednisolone 100 mg intravenous or its equivalent 30 minutes prior to each infusion are recommended to reduce the incidence and severity of infusion reactions
Mechanism
  • B-cell depleting agent - Rituxan is a genetically engineered chimeric murine/human monoclonal IgG1 kappa antibody directed against the CD20 antigen. Rituxan targets the CD20 antigen expressed on the surface of pre-B and mature B-lymphocytes. Upon binding to CD20, Rituxan mediates B-cell lysis.

Indications (FDA-approved)
  • Rheumatoid arthritis
  • Non–Hodgkin's lymphoma
  • Chronic Lymphocytic Leukemia (CLL)
  • Granulomatosis with Polyangiitis (GPA) (Wegener's Granulomatosis) and Microscopic Polyangiitis (MPA)
NOTE: Only side effects that occurred at an incidence of ≥ 3% and ≥ 2% more than placebo are listed. Data is from RA trials.

  • Infusion reactions - up to 32% of patients during first infusion; reactions include fever, chills, rigors, pruritus, urticaria/rash, angioedema, sneezing, throat irritation, cough, bronchospasm, and hypertension; reactions decreased with subsequent infusions
  • Hypertension - 8%, P - 5%
  • Nausea - 8%, P - 5%
  • Arthralgia - 6%, P - 4%
  • Fever - 5%, P - 2%
  • Dyspepsia - 3%, P - < 1%
NOTE: Precautions presented here are for patients with RA. Precautions in patients with malignancies may differ.

  • Tuberculosis (TB) - test patients for TB before use (≥ 5 mm induration should be considered positive). The American College of Rheumatology recommends treating latent TB for at least one month before starting rituximab. Active TB should be treated completely before starting rituximab. [2]
  • Infusion reactions - fatal infusion reactions have occurred. Patients should be premedicated with methylprednisolone 100 mg IV or its equivalent 30 minutes prior to each infusion.
  • Mucocutaneous reactions - fatal mucocutaneous reactions have occurred. Reactions include paraneoplastic pemphigus, Stevens-Johnson syndrome, lichenoid dermatitis, vesiculobullous dermatitis, and toxic epidermal necrolysis.
  • Hepatitis B reactivation - hepatitis B reactivation leading to death has occurred. Screen all patients for hepatitis B infection by measuring HBsAg and anti-HBc before initiating treatment with Rituxan. For positive results (HBsAg positive [regardless of antibody status] or HBsAg negative but anti-HBc positive), consult hepatitis B expert before starting therapy. Monitor patients with current or prior infection closely.
  • Progressive Multifocal Leukoencephalopathy (PML) - JC virus infections resulting in PML and death have occurred. The majority of cases occurred in patients receiving chemotherapy or as part of a hematopoietic stem cell transplant. Consider PML in any patient presenting with new-onset neurologic manifestations.
  • Serious infections - Rituxan may increase the risk of serious infections including invasive fungal infections, bacterial infections, viral infections, and others. In RA trials, the rate of serious infections in Rituxan-treated patients was 4.31 per 100 patient-years. The most common serious infections were pneumonia or lower respiratory tract infections, cellulitis and urinary tract infections.
  • Cardiac reactions - cardiac reactions including arrhythmia and heart attack have occurred in patients treated with Rituxan. Susceptible patients should have cardiac monitoring during infusions.
  • Rituxan antibodies - in trials, anti-Rituxan antibodies were detected in up to 23% of patients. It's unclear if antibody development is associated with reduced efficacy and/or an increase in hypersensitivity reactions.
  • Vaccines - patients may receive non-live vaccines. Administer non-live vaccines at least 4 weeks prior to a course of Rituxan. Vaccine response may be lower in patients receiving Rituxan. Do not give live or attenuated vaccines (e.g. MMR, Varicella, BCG).
  • Hypophosphatemia - in trials, newly-occurring hypophosphatemia (< 2.0 mg/dl) was observed in 21% of Rituxan-treated patients. The majority of the observed hypophosphatemia occurred at the time of the infusions and was transient.
  • Hyperuricemia - in trials, newly-occurring hyperuricemia (> 10 mg/dl) was observed in 1.5% of Rituxan-treated patients compared to 0.3% of placebo-treated patients.
  • Liver disease - has not been studied
  • Kidney disease - has not been studied




Drug Dosage form Dosing Other Mechanism/FDA-approved indications Side effects
P = % of patients on placebo who experienced side effect
Contraindications/Precautions
Abatacept

(Orencia®)
Prefilled syringe
  • 50 mg/0.4 ml
  • 87.5 mg/0.7 ml
  • 125 mg/ml
  • Comes in package of 4 syringes

Single-use vials
  • Comes in 250 mg vial
Rheumatoid arthritis
  • Prefilled syringe (subcutaneous)
    • Dosing: 125 mg subcutaneously once weekly
    • May give IV loading dose per guidelines below
    • If IV loading dose is given, initiate first subcutaneous dose within a day of IV loading dose
    • If transitioning from IV therapy to subcutaneous, administer the first subcutaneous dose instead of the next scheduled intravenous dose
  • Intravenous
    • Starting: weight-based dose at Week 0, 2, and 4
    • Maintenance: weight-based dose every 4 weeks
Body weight (kg) Dose # of vials
< 60 kg 500 mg 2
60 - 100 kg 750 mg 3
> 100 kg 1000 mg 4

Juvenile idiopathic arthritis
  • Prefilled syringe - subcutaneous (≥ 2 years old)
  • Body weight (kg) Dose (once weekly)
    10 to less than 25 kg 50 mg
    25 to less than 50 kg 87.5 mg
    ≥ 50 kg 125 mg

  • Intravenous (≥ 6 years old)
    • Starting: 10 mg/kg at Week 0, 2, and 4
    • Maintenance: 10 mg/kg dose every 4 weeks
    • If weight is ≥ 75 kg, use adult dosing
Prefilled syringe
  • Keep refrigerated
  • Solution should be clear and colorless to pale yellow
  • Let syringe warm to room temperature for 30 - 60 minutes before injecting
  • Inject subcutaneously in the thigh, abdomen, or outer upper arms. Rotate injection sites.

Intravenous infusion
  • Orencia is infused over 30 minutes
Mechanism
  • T-cell inhibitor - Orencia is a soluble fusion protein that consists of the extracellular domain of human cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) linked to the modified Fc portion of human immunoglobulin G1 (IgG1). Orencia inhibits T-lymphocyte activation by binding to CD80 and CD86, thereby blocking interaction with CD28. CD28 interaction is necessary for full activation of T-lymphocytes.

Indications (FDA-approved)
  • Rheumatoid arthritis - as monotherapy or concomitantly with DMARDs other than TNF inhibitors
  • Juvenile idiopathic arthritis - in patients ≥ 2 years old as monotherapy or with methotrexate
NOTE: Only side effects that occurred at an incidence of ≥ 3% and ≥ 2% more than placebo are listed.

  • Headache - 18%, P - 13%
  • Nasopharyngitis - 12%, P - 9%
  • Dizziness - 9%, P - 7%
  • Hypertension - 7%, P - 4%
  • Dyspepsia - 6%, P - 4%
  • Injection site reactions - 2.6% of patients; reactions include hematoma, pruritus, and erythema
  • Infusion reactions - 9% of patients; most common reactions include dizziness, headache, and hypertension
  • TNF inhibitors - DO NOT COMBINE. May increase risk of serious infection.
  • Infusion reactions - rare cases of anaphylaxis have been reported with Orencia infusion. Administer under medical supervision.
  • Tuberculosis (TB) - test patients for TB before use (≥ 5 mm induration should be considered positive). The American College of Rheumatology recommends treating latent TB for at least one month before starting abatacept. Active TB should be treated completely before starting abatacept. [2]
  • Hepatitis B - patients infected with hepatitis B may have reactivation of disease while taking Orencia. Test patients before initiating therapy. Monitor infected patients closely.
  • Vaccines - patients may receive non-live vaccines. Do not give live or attenuated vaccines (e.g. MMR, Varicella, BCG) concurrently with Orencia or within 3 months of discontinuation.
  • COPD - patients with COPD had a greater number of adverse events (COPD exacerbations, cough, rhonchi, dyspnea) while using Orencia. Use caution in this population.
  • Serious infections - Orencia may increase the risk of serious infections including tuberculosis, invasive fungal infections, bacterial infections, viral infections, and others. In trials, the incidence of serious infections in Orencia-treated patients was 3% compared to 1.9% in placebo-treated patients. The most common serious infections were pneumonia, cellulitis, urinary tract infection, bronchitis, diverticulitis, and acute pyelonephritis.
  • Malignancies - Orencia may increase the risk for certain cancers, particularly lymphoma and lung cancer
  • Orencia antibodies - in trials, anti-Orencia antibodies were detected in up to 10% of patients. It's unclear if antibody development is associated with reduced efficacy and/or an increase in hypersensitivity reactions.
  • Blood glucose test strips (infusion) - maltose in the Orencia infusion may cause falsely elevated blood glucose readings on the day of infusion with certain test strips and monitors.
  • Liver disease - has not been studied
  • Kidney disease - has not been studied

Drug Dosage form Dosing Mechanism/FDA-approved indications Side effects
P = % of patients on placebo who experienced side effect
Contraindications/Precautions
Natalizumab

(Tysabri®)
Single-use vials
  • Comes in 300 mg vial
Crohn's disease
  • Dosing: 300 mg every 4 weeks
  • If benefit is not seen by 12 weeks, discontinue
  • For patients using steroids, begin tapering steroids as soon as benefit from Tysabri is seen. If steroids cannot be tapered within 6 months, discontinue Tysabri.
  • Tysabri is given by IV infusion over 1 hour
  • Because of the risk of PML, providers must be enrolled in the Tysabri CD TOUCH program in order to prescribe Tysabri
Mechanism
  • T-cell inhibitor - Tysabri is a recombinant humanized IgG4ϰ monoclonal antibody that binds to the α4-subunit of α4β1 and α4β7 integrins expressed on the surface of all leukocytes except neutrophils, and inhibits the α4-mediated adhesion of leukocytes to their counter-receptor(s). Inhibiting this interaction prevents transmigration of leukocytes across the endothelium into inflamed parenchymal tissue

Indications (FDA-approved)
  • Crohn's disease
  • Multiple sclerosis
NOTE: Only side effects that occurred at an incidence of ≥ 2% more than placebo are listed. Data is from Crohn's disease studies.

  • Headache - 32%, P - 23%
  • Upper respiratory infection - 22%, P - 16%
  • Nausea - 17%, P - 15%
  • Fatigue - 10%, P - 8%
  • Arthralgia - 8%, P - 6%
  • Throat pain - 6%, P - 4%
  • Rash - 6%, P - 4%
  • Dyspepsia - 5%, P - 3%
  • Constipation - 4%, P - 2%
  • Vaginal infections - 4%, P - 2%
  • Urinary tract infections - 3%, P - 1%
  • Cough - 3%, P - <1%
  • Infusion reactions - in Crohn's trials, up to 11% of patients; most common reactions include headache, nausea, urticaria, pruritus, and flushing
  • Progressive Multifocal Leukoencephalopathy (PML) - JC virus infections resulting in PML and death have occurred. Longer duration of treatment (> 2 years), prior treatment with other immunosuppressants, and presence of anti-JCV antibodies are all risk factors for PML. Baseline MRI may help to distinguish new lesions in the future. Consider PML diagnosis in patients with new-onset or deteriorating neurological signs and symptoms.
  • Herpes encephalitis and meningitis - Tysabri increases the risk
  • Hepatotoxicity - cases of acute hepatitis and liver failure have occurred.
  • Hypersensitivity reactions - hypersensitivity reactions including anaphylaxis have occurred. Reactions are more common in patients who develop anti-Tysabri antibodies. See Tysabri antibodies below.
  • Serious infections - Tysabri may increase the risk of serious infections including invasive fungal infections, bacterial infections, viral infections, and others. In Crohn's trials, the incidence of serious infections in Tysabri-treated patients was 3.3% compared to 2.8% in placebo-treated patients.
  • Tysabri antibodies - in Crohn's trials, anti-Tysabri antibodies were detected in up to 10% of patients. Antibody development was associated with reduced efficacy and an increase in hypersensitivity reactions. Patients who receive 1 - 2 infusions of Tysabri followed by an extended period without exposure are at greater risk of developing antibodies and experiencing hypersensitivity reactions. Before restarting therapy, antibody testing may be appropriate.
  • TNF inhibitors - DO NOT COMBINE. May increase risk of PML.
  • Immunosuppressants - DO NOT COMBINE. May increase risk of PML.
  • Corticosteroids - taper corticosteroids when starting Tysabri.
  • Increase in blood counts - Tysabri increases circulating lymphocytes, monocytes, eosinophils, basophils, and nucleated red blood cells. Levels return to normal when Tysabri is discontinued.
  • Decrease in hemoglobin - Tysabri induces mild decreases in hemoglobin levels (mean decrease of 0.6 g/dl) that are frequently transient
  • Vaccines - patients may receive non-live vaccines. Do not give live or attenuated vaccines (e.g. MMR, Varicella, BCG).
  • Liver disease - has not been studied
  • Kidney disease - has not been studied

Drug Dosage form Dosing Mechanism/FDA-approved indications Side effects
P = % of patients on placebo who experienced side effect
Contraindications/Precautions
Vedolizumab

(Entyvio®)
Single-use vials
  • 300 mg vial
Crohn's disease
  • Starting: 300 mg IV at Weeks 0, 2, and 6
  • Maintenance: 300 mg IV every 8 weeks
  • Entyvio is given by IV infusion over 30 minutes
  • Discontinue if no effect seen after Week 14

Ulcerative colitis
  • Starting: 300 mg IV at Weeks 0, 2, and 6
  • Maintenance: 300 mg IV every 8 weeks
  • Entyvio is given by IV infusion over 30 minutes
  • Discontinue if no effect seen after Week 14
Mechanism
  • T-cell inhibitor - Vedolizumab is a humanized monoclonal antibody that specifically binds to the α4β7 integrin and blocks the interaction of α4β7 integrin with mucosal addressin cell adhesion molecule-1 (MAdCAM-1) and inhibits the migration of memory T-lymphocytes across the endothelium into inflamed gastrointestinal parenchymal tissue

Indications (FDA-approved)
  • Crohn's disease - treatment of active disease in patients who did not respond to or tolerate tumor necrosis factor inhibitors, immunosuppressants, or corticosteroids
  • Ulcerative colitis - treatment of active disease and maintenance of remission in patients who did not respond to or tolerate tumor necrosis factor inhibitors, immunosuppressants, or corticosteroids
NOTE: Only side effects that occurred at an overall incidence of ≥ 3% and at an incidence ≥ 2% more than placebo are listed. Data below has been combined from Crohn's disease and ulcerative colitis studies.

  • Nasopharyngitis - 13%, P - 7%
  • Arthralgia - 12%, P - 10%
  • Fever - 9%, P - 7%
  • Fatigue - 6%, P - 3%
  • Cough - 5%, P - 3%
  • Influenza - 4%, P - 2%
  • Itching - 3%, P - 1%
  • Sinusitis - 3%, P - 1%
  • Oropharyngeal pain - 3%, P - 1%
  • Pain in extremities - 3%, P - 1%
  • Infusion reactions - up to 4% of patients; most common reactions include nausea, headache, pruritus, dizziness, fatigue, pyrexia, urticaria, and vomiting
  • Hypersensitivity reactions - hypersensitivity reactions including anaphylaxis have occurred. In trials, 1 patient out of 1434 had an anaphylactic reaction during Entyvio infusion.
  • Serious infections - Entyvio may increase the risk for serious infections. In trials, the rate of serious infections was 0.07 per patient-year in Entyvio-treated patients compared to 0.06 per patient-year in placebo-treated patients. Serious infections were more frequent in Crohn's disease patients than ulcerative colitis patients. Anal abscesses were the most frequently reported serious infection in Crohn's patients.
  • Progressive Multifocal Leukoencephalopathy (PML) - another integrin inhibitor (Tysabri) has been associated with JC virus infections resulting in PML. In Entyvio trials lasting at least 24 months, no cases of PML were observed. An association between Entyvio and PML cannot be ruled out. Consider PML diagnosis in patients with new-onset or deteriorating neurological signs and symptoms.
  • Hepatotoxicity - in rare cases, hepatotoxicity has occurred with Entyvio. In controlled trials, AST and ALT elevations ≥ 3 X ULN occurred in < 2% of patients.
  • Vaccines - patients may receive non-live vaccines. The risks of administering live or attenuated vaccines with Entyvio therapy are unknown. Ideally, all vaccines should be brought up to date before initiating Entyvio.
  • Malignancies - Entyvio may increase the risk of malignancy
  • Entyvio antibodies - in trials, anti-Entyvio antibodies were detected in up to 13% of patients. Antibody development was associated with reduced efficacy.
  • Natalizumab (Tysabri) - DO NOT COMBINE. May increase risk of PML.
  • TNF inhibitors - DO NOT COMBINE. May increase risk of serious infection.
  • Liver disease - has not been studied
  • Kidney disease - has not been studied




Drug Dosage form Dosing Other Mechanism/FDA-approved indications Side effects
P = % of patients on placebo who experienced side effect
Contraindications/Precautions
Intravenous immunoglobulin

(IVIG)
In the U.S., available IVIG products include the following:
  • Bivigam®
  • Carimune®
  • Flebogamma® Dif
  • Gammagard®
  • Gammagard® S/D
  • Gammaplex®
  • Gamunex-C®
  • Octagam®
  • Privigen®
NOTE: Dosing recommendations vary slightly by product. Doses presented here are general recommendations.

Primary humoral immunodeficiency
  • 0.3 - 0.8 grams/kg every 3 - 4 weeks

Immune thrombocytopenia
  • 1 gram/kg as a one-time dose. May repeat if necessary.
  • Alternatively, 0.4 grams/kg/day can be given on 2 - 5 consecutive days as needed

Kawasaki syndrome
  • 1 gram/kg as a one-time dose
  • Alternatively, 0.4 grams/kg/day for 4 consecutive days
  • Dosing from Gammagard S/D PI

Multifocal motor neuropathy
  • 0.5 - 2.4 grams/kg/month
  • Dosing from Gammagard PI

Chronic Inflammatory Demyelinating Polyneuropathy
  • Loading dose: 2 grams/kg
  • Maintenance: 1 gram/kg every 3 weeks
  • Dosing from Gamunex-C PI

Guillain–Barré syndrome
  • 0.4 grams/kg/day for 5 consecutive days [3]

Myasthenia gravis
  • 1 - 2 grams/kg/dose [3]

Kidney transplant (highly sensitized to HLA)
  • 2 grams/kg/month for 4 months before transplant [3]

  • IVIG is typically given intravenously over the course of 1 - 5 days depending on the dose and the patient
  • Some products (e.g. Gammagard) can be infused subcutaneously through a pump
Mechanism
  • Primary humoral immunodeficiency - IVIG replaces deficient antibodies
  • Autoimmune disorders - there are a number of theories on how IVIG causes immunosuppression. Proposed mechanisms include the following:
    • Binding and neutralization of autoantibodies
    • Blockade of Fcγ receptors on macrophages thereby inhibiting phagocytosis
    • Up regulation of Fcγ receptor IIB on macrophages. Fcγ receptor IIB down regulates the inflammatory cascade.
    • Binding of complement components and blocking their activation
    • Decreasing the half-life of autoantibodies [3,4]

Indications (FDA-approved)
  • Primary humoral immunodeficiency
  • Immune thrombocytopenia
  • Kawasaki syndrome
  • Multifocal motor neuropathy
  • Chronic Inflammatory Demyelinating Polyneuropathy
NOTE: Information below is from study in Privigen PI where median dose was 0.430 grams/kg in patients with primary humoral immunodeficiency.

  • Headache - 45%
  • Fatigue - 16%
  • Nausea - 14%
  • Chills - 11%
  • Vomiting - 11%
  • Back pain - 10%
  • Pain - 9%
  • Fever - 9%
  • Diarrhea - 8%
  • Cough - 6%
  • Stomach discomfort - 6%
NOTE: General contraindications/precautions are listed below. See the individual product PI for specific product information.
  • Sensitivity reactions - severe sensitivity reactions may occur, even in patients who have tolerated previous infusions. Appropriate precautions should be taken.
  • IgA deficiency - all IVIG products contain small amounts of IgA. Patients with IgA deficiency may have antibodies to IgA. These patients are at increased risk of severe hypersensitivity reactions to IVIG. Gammagard S/D contains the least amount of IgA.
  • Kidney dysfunction/failure - IVIG can cause kidney dysfunction/failure in some patients. IVIG products that contain sucrose (e.g. Carimune) carry a higher risk. Use caution in susceptible patients (e.g. pre-existing kidney disease, diabetes, ≥ 65 years old, volume depletion, sepsis, paraproteinemia, concomitant nephrotoxic drugs).
  • Thrombosis - IVIG may increase the risk of venous and arterial thrombosis. Use caution in patients with risk factors for thrombosis (e.g. immobilization, hypercoagulable states, history of thrombosis, estrogen use, indwelling catheters, hyperviscosity).
  • Increased serum viscosity - IVIG infusions increase serum proteins which may increase serum viscosity. Ensure adequate hydration and check blood viscosity in at-risk patients (e.g. cryoglobulins, very high triglycerides, monoclonal gammopathies).
  • Hyperproteinemia and pseudohyponatremia - IVIG infusions increase serum proteins. The increase in serum proteins may cause pseudohyponatremia because the plasma water fraction in blood samples is reduced leading to false sodium concentration measurements. Providers should distinguish true hyponatremia from pseudohyponatremia in patients receiving IVIG, because treatment of hyponatremia may increase blood viscosity.
  • Aseptic meningitis - aseptic meningitis has occurred in patients receiving IVIG. Symptoms (e.g. severe headache, nuchal rigidity, photophobia, painful eye movements) usually begin within several hours to 2 days of receiving treatment. Discontinuation of IVIG typically leads to resolution within 2 days.
  • Hemolysis - blood group antibodies in IVIG may cause hemolysis. Higher doses of IVIG (≥ 2 grams/kg) and non-O blood types in recipients may be risk factors. Check hemoglobin levels in high-risk patients before therapy, within 36 hours of the start of therapy, and at 7 - 10 days.
  • Transfusion-related acute lung injury (TRALI) - TRALI, a syndrome of noncardiogenic pulmonary edema, has occurred in patients receiving IVIG. Symptoms typically occur within 1 - 6 hours following treatment. If TRALI is suspected, testing for anti-neutrophil antibodies and anti-human leukocyte antigen (HLA) antibodies in both the IVIG product and the patient's serum should be performed.
  • Live vaccines - IVIG infusions may impair the efficacy of live vaccines such as mumps, rubella, and varicella for up to 6 months and measles for up to a year
  • Volume overload - IVIG infusions often contain a large volume of fluid. Use caution in susceptible patients (e.g. CHF, kidney disease)
  • Potential for infection transfer - because IVIG is a blood product, the potential for the transmission of infectious agents exists
  • Blood glucose monitoring - some IVIG products (e.g. Octagam) contain maltose which can be falsely interpreted as glucose by some glucometers
  • Serologic antibody tests - passively transferred antibodies from IVIG may cause false-positive serological testing (e.g. infection/immunity testing, direct or indirect antiglobulin testing, detection of beta-D-glucans for diagnosis of fungal infections)
  • Liver disease - manufacturer makes no recommendation
  • Kidney disease - use caution. May worsen kidney disease.



  • PRICING

    • All biologicals are very expensive
    • One month of therapy costs thousands of dollars



  • REFERENCES
    • 1 - Manufacturer's package insert for listed drug
    • 2 - PMID 26545940 - ACR RA GL 2015
    • 3 - PMID 25667260 - Intravenous immunoglobulin as clinical immune-modulating therapy, CMAJ 2015
    • 4 - PMID 23171098 - Intravenous Immune Globulin in Autoimmune and Inflammatory Diseases, NEJM 2012