A systematic review of abatacept and belatacept in immune-mediated diseases
In brief
Abatacept benefits patients with over a dozen off-label autoimmune diseases
A systematic review of 96 reports found abatacept effective in conditions such as Sjögren's syndrome, systemic sclerosis subtypes, lupus arthritis, inflammatory myopathies and giant-cell arteritis, with lower-level evidence supporting use in granulomatosis with polyangiitis, sarcoidosis and ocular inflammation. Belatacept showed limited off-label use mainly in transplant-related kidney disease and rare CTLA-4 deficiency.
- Journal
- Journal of autoimmunity (Q1)
- Published
- 7 August 2026
- Study design
- Systematic review / meta-analysis of RCTs
- Evidence level
- Level 1, High (CEBM 1a)
- Authors
- Alissa M Krek, Dennis D Arnold, Alina C Martin, Miro E Raeber
- PMID
- 42567048
- DOI
- 10.1016/j.jaut.2026.103608
Why clinicians should know about it
- Picked for Immunology and Allergy (top studies of the week, 9 August 2026).
- Picked for Transplantation (top studies of the week, 9 August 2026): High-quality evidence in a top journal
- Picked for Rheumatology (top studies of the week, 9 August 2026).
Abstract
BACKGROUND: Abatacept (ABA) and belatacept (BEL) are immunomodulatory fusion proteins in which the extracellular domain of cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) is linked to the Fc fragment of human IgG1. Functionally, they bind to cell surface antigens CD80 and CD86 on antigen-presenting cells, thereby preventing CD28-mediated costimulatory signaling. This systematic review aims to evaluate the clinical efficacy of ABA and BEL in immune-mediated diseases, focusing on indications currently not approved by the United States Food and Drug Administration (FDA) or the European Medicines Agency (EMA). METHODS: We searched PubMed and Web of Science for reports describing clinical efficacy of ABA or BEL in at least one patient with immune-mediated conditions outside FDA/EMA-approved indications. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist guided our data reporting. RESULTS: Of 5333 articles initially extracted, 2778 unique records were screened after de-duplication, and 96 matched our criteria and were included in this study. ABA was beneficial in patients diagnosed with Sjögren's syndrome (particularly secondary forms); autoimmunity in association with immunodeficiency; early, inflammatory and normal-like subtypes of systemic sclerosis; scleroderma; arthritis in systemic lupus erythematosus; inflammatory myopathies (polymyositis, immune-mediated necrotizing myositis, and antisynthetase syndrome); and giant-cell arteritis. Lower-level evidence studies reported positive results using ABA to treat granulomatosis with polyangiitis; relapsing polychondritis; sarcoidosis; and inflammatory eye diseases. Results of several studies highlighted the positive impact of ABA on arthritis in patients taking this drug for other indications. Likewise, several autoimmune diseases responded effectively to ABA when used to treat concomitant rheumatoid arthritis. Positive serological responses suggesting downstream modulation of B cell activation were reported in several randomized controlled trials. BEL was used after kidney transplantation in patients with proteinuric kidney disease or lupus nephritis, and in a few non-transplanted CTLA-4 haploinsufficiency carriers for immunodeficiency-associated autoimmunity. CONCLUSIONS: Our results provide a comprehensive summary of the efficacy of ABA and BEL across a broad spectrum of autoimmune diseases.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.