What T cell targeted therapies are available and how are they used?
Abatacept (Orencia): a fully human fusion protein comprising the extracellular portion of CTLA4 and the Fc fragment of IgG1 (CTLA4Ig). Abatacept binds to CD80/CD86 on antigen-presenting cells (APCs) preventing these molecules from binding to their ligand, CD28, on T cells. This interferes with optimal T-cell activation resulting in decreased production of proinflammatory cytokines. Notably, T-cell activation is not completely inhibited because other interactions between APCs and T cells (ICAM-1:LFA-1; CD40:CD40L; LFA-3:CD-2) are not inhibited.
- • FDA-approved indication: RA, adult PsA, and polyarticular JIA (age >2 years) who are inadequate responders to DMARDs (MTX). Can use with csDMARDs (MTX).
- • Available formulation: single-use vial containing 250 mg of lyophilized powder for reconstitution for IV infusion; also available are 50-, 87.5-, and 125-mg single-dose prefilled syringes and a 125-mg single-dose ClickJect autoinjector for SC administration.
- • IV dose: weight based (adults with RA or PsA: 500 mg if <60 kg; 750 mg if 60–100 kg; 1000 mg if >100 kg); (child with JIA: 10 mg/kg if <75 kg; same as adult dose if >75 kg). Loading dose at 0, 2, and 4 weeks, then every 4 weeks. Does not need premedication. Infusion takes 30 minutes.
- • SC dose: adult RA or PsA: 125 mg SC weekly with or without IV loading dose. Child with JIA: 10 to <25 kg: 50 mg weekly; 25 to 50 kg: 87.5 mg weekly; >50 kg: 125 mg weekly.
- • Follow-up: routine monitoring for csDMARDs.
- • Adverse reactions:
- • Infusion reactions: rare. Routine premedication not necessary.
- • Infections: routine similar to placebo. Serious infections (3%). Pneumonias increased in patients with chronic obstructive pulmonary disease. Opportunistic infections rare (0.01–0.05 events/100 patient years). Abatacept may be the safest biologic to use in patients at risk for contacting TB.
- • Malignancy: standardized incidence rates for lung cancer, lymphoma, and other malignancies not increased over background rates of patients with RA who are not on biologics.
- • Immunizations: response to killed/inactivated vaccines may be decreased.
- • Others: headache. No increased rate of demyelinating disease, autoimmune phenomenon, CHF, hematologic abnormalities.
- • Precautions: do not use in patients with active infection.
- • Other diseases: being tested in SLE, inflammatory myopathies, GCA, and Takayasu’s arteritis.
