T Cell Costimulation Inhibitors

T cell costimulation inhibitors block the second signal needed to activate T cells. Abatacept (CTLA4-Ig) is used in rheumatoid arthritis, psoriatic arthritis and juvenile arthritis; belatacept is used in kidney transplantation. They have a lower serious infection rate than TNF inhibitors in older patients, but a slower onset.

Mechanism. Abatacept and belatacept bind CD80 and CD86 on antigen-presenting cells, preventing CD28 binding and T cell activation. They reduce T cell proliferation and cytokine release without depleting T cells.

Pharmacokinetics. Fusion proteins with half-lives of about 13 days (abatacept) and 8 days (belatacept). Antidrug antibodies are uncommon.

Abatacept dosing.

• Intravenous: 500 mg (under 60 kg), 750 mg (60 to 100 kg), 1000 mg (over 100 kg) at weeks 0, 2, 4 and then every 4 weeks.
• Subcutaneous: 125 mg weekly (with or without an intravenous loading dose).
• Juvenile idiopathic arthritis: 10 mg/kg intravenously (up to 1000 mg) at weeks 0, 2, 4, then every 4 weeks; subcutaneous doses by weight.
• Response takes 12 weeks or longer; review at 3 to 6 months.

Belatacept dosing. 10 mg/kg intravenously on days 1 and 5, then at weeks 2, 4, 8 and 12, then 5 mg/kg every 4 weeks, with mycophenolate and glucocorticoid (kidney transplant).

Combination. Abatacept with methotrexate is more effective than alone. Avoid combination with other biologics.

• First-line. Rheumatoid arthritis after csDMARD failure in selected patients (rheumatoid factor or anti-CCP positive disease responds best).
• Alternative. After TNF inhibitor failure; patients with recurrent infection risk, older adults, or interstitial lung disease.
• Specialist. Psoriatic arthritis, juvenile arthritis, graft-versus-host disease prophylaxis, kidney transplantation (belatacept).
• Emergency. None.

Selection. Consider when infection risk matters most (older patients, lung disease) and when a slower onset is acceptable. It does not help axial spondyloarthritis or psoriasis.

Contraindications. Active serious infection; hypersensitivity; belatacept in patients seronegative for Epstein-Barr virus or with unknown status; liver transplant (belatacept).

Serious adverse effects.

• Infections (upper respiratory, pneumonia, tuberculosis reactivation).
• Infusion reactions; headache, nausea.
• Worsening of chronic obstructive pulmonary disease with exacerbations (abatacept).
• Post-transplant lymphoproliferative disorder (belatacept; Epstein-Barr virus positive recipients only).
• Possible modest skin cancer risk.

Major interactions. TNF inhibitors and other biologics (more infection; avoid); live vaccines; blood glucose meters reading falsely high with maltose in the intravenous formulation.

Common prescribing errors.

• Combining with another biologic.
• Using maltose-sensitive glucose meters in diabetic patients on intravenous abatacept.
• Stopping before 3 to 6 months.
• Missing tuberculosis and hepatitis B screening.
• Using belatacept without checking Epstein-Barr virus status.

Special groups.

• Pregnancy: limited data; avoid unless essential.
• Breastfeeding: unknown; avoid.
• Children: licensed for juvenile arthritis from 2 years; weight-based.
• Older adults: lower infection rates than TNF inhibitors; useful.
• Kidney: no adjustment.
• Liver: no adjustment.
• East Africa: tuberculosis, hepatitis B and HIV screening before use; availability is limited and cost high; slower onset means alternatives such as triple csDMARD therapy remain important.

Monitoring. Disease activity every 3 months; infection symptoms; chest symptoms in lung disease; tuberculosis symptoms yearly; Epstein-Barr virus and graft function with belatacept.

Referral and escalation. Serious infection; no response at 6 months; respiratory deterioration; transplant rejection.

Comparison with alternative classes. Abatacept has a favourable infection profile and suits older patients and those with lung disease, but works more slowly than TNF or IL-6 inhibitors. Belatacept protects kidney grafts better than calcineurin inhibitors but needs infusion visits.