GolimumabRx

Trade Names: Simponi, Simponi Aria

Drug Class: Biologic DMARD, TNF antagonist

Preparations:
Simponi: Subcutaneous injection 50 mg/0.5 ml and  100 mg/1 ml prefilled syringes or prefilled autoinjector
Simponi Aria: IV solution 50 mg/4ml

Dose: For RA, psoriatic arthritis, ankylosing spondylitis 50 mg subcutaneous injection once a month, or for RA 2 mg/kg IV infusion at weeks 0, 4 and then every 8 weeks. For ulcerative colitis 200 mg subcutaneous injection at week 0, followed by 100 mg at week 2 and then 100 mg every 4 weeks.

Indications: RA, psoriatic arthritis, ankylosing spondylitis, ulcerative colitis

Mechanism of Action: A human monoclonal antibody against TNF-alpha that blocks the effects of the cytokine.

Contraindications: Hypersensitivity, untreated tuberculosis and other opportunistic infections, sepsis, active infection, chronic localized or recurrent infections, demyelinating disease, optic neuritis, moderate-to-severe heart failure.

Precautions: Increased risk of serious infections including TB and fungal. Exclude latent or active TB with a skin test or TB blood test (interferon-gamma release assays or IGRA). Caution in debilitated or high risk of infection.  Exclude active hepatitis B infection or carriage.  Avoid live virus vaccines and BCG. Do not use with other biologics. May exacerbate pre-existing demyelinating disease and heart failure.

Monitoring: Monitor clinically for infection. CBC periodically. After therapy started, additional  TB testing may be indicated for individuals likely to have exposure to TB.

Pregnancy Risk: B

Adverse Effects
Common: Injection site reactions (subcutaneous), minor infusion reactions (IV), positive antinuclear antibody, positive antinuclear and double stranded DNA antibody.
Less common: Serious infusion reactions, allergy, infection (bacterial, but particularly opportunistic infections such as tuberculosis, listeriosis, and histoplasmosis).
Rare: Anaphylaxis, lymphoma (including fatal hepatosplenic T-cell lymphoma), hepatitis, demyelinating CNS disorders, optic neuritis, seizures, pancytopenia, drug-induced lupus, reactivation of hepatitis B, new onset psoriasis.

Drug Interactions: Concurrent use of high-dose steroids and other immunosuppressants may increase risk of infection.

Patient Instructions: Avoid live virus vaccines; avoid pregnancy; stop injections and call your doctor if an infection or fever develops that lasts more than a few days.

Comments: TNF antagonists are among the most effective treatments for RA. Patients start to respond quickly, usually within 4–6 weeks but maximum response may take 4-6 months. Combined therapy with MTX is more effective than either drug alone. TNF antagonists are being explored in a range of diseases such as sarcoidosis and inflammatory eye disease. Risk of tuberculosis may be lower with etanercept than other TNF antagonists; comparative risk of adverse effects among individual TNF antagonists is not clear and side effects likely a class effect. Patients may form antibodies to anti-TNF drugs that decrease their effect. Concurrent treatment with MTX may reduce the frequency of this.

Clinical Pharmacology: Half-life is 14 days. Biologic agents are not metabolized and thus have few drug interactions.

Cost: $$$$$

BIBLIOGRAPHY

Bombardier C, Hazlewood GS, Akhavan P, et al. Canadian Rheumatology Association recommendations for the pharmacological management of rheumatoid arthritis with traditional and biologic disease-modifying antirheumatic drugs: part II safety. J Rheumatol 2012;39:1583-602. PMID: 22707613.

Singh JA, Furst DE, Bharat A. et al.2012 Update of the 2008 American College of Rheumatology recommendations for the use ofdisease-modifying antirheumatic drugs and biologic agents in the treatment of rheumatoid arthritis.Arthritis Care Res 2012;64(5):625-39.PMID:22473917