If MTX or TNFi fail, which is a next-line option?

• A. Anakinra
• B. Abatacept
• C. Rituximab
• D. Jak inhibitor

Answer: (B)

When methotrexate or a TNF inhibitor hasn’t controlled the disease, switching to a therapy with a different mechanism can offer additional benefit. Abatacept works by blocking the costimulatory signal needed for full T-cell activation (CTLA-4-Ig prevents CD28 from binding CD80/86), which dampens the entire inflammatory cascade driving rheumatoid arthritis. This distinct mode of action makes it a good next-line option after TNF inhibitors, because it targets the immune response in a way TNF blockade does not. In patients who did not respond adequately to MTX or TNFi, abatacept has shown meaningful improvement and is generally well tolerated, with a safety profile that is manageable alongside conventional DMARDs. Other options exist (anakinra is less effective in RA; rituximab targets B cells; JAK inhibitors are effective but carry specific safety considerations), but abatacept’s mechanism and clinical experience often make it a preferred next step after TNFi failure.