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Rheumatoid arthritis — SCE Rheumatology MCQ

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ModerateInflammatory ArthritisRheumatoid arthritisSCE Rheumatology

A 62-year-old man with seropositive erosive rheumatoid arthritis has persistent synovitis despite 6 months of methotrexate 25 mg weekly and sulfasalazine 1 g twice daily at maximally tolerated doses. Adherence is confirmed and his DAS28-CRP is 5.7. He has had no serious infections, and screening for tuberculosis and viral hepatitis is negative. He had a non-ST-elevation myocardial infarction 4 years ago and continues to smoke, with a 30 pack-year history. Advanced therapy in combination with methotrexate is being considered. Which treatment proposal should be reserved for use only if no suitable alternative is available?

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Correct answer: E — Initiate upadacitinib with methotrexate

This patient has severe active rheumatoid arthritis despite intensive combination conventional DMARD therapy, so he meets the disease-activity and treatment-sequence criteria for escalation to an advanced therapy. The decisive features are his established atherosclerotic cardiovascular disease and current long-term smoking. Upadacitinib is a JAK inhibitor. UK MHRA advice treats the increased risks of major adverse cardiovascular events, malignancy, venous thromboembolism, serious infection and mortality as class effects of JAK inhibitors. In patients with a history of atherosclerotic cardiovascular disease, other cardiovascular risk factors, or current or past long-term smoking, a JAK inhibitor should be used only when no suitable treatment alternative is available. His age being below 65 years does not remove this restriction because he independently meets two other risk criteria. Adalimumab and certolizumab pegol are TNF inhibitors, while abatacept and tocilizumab are non-TNF biological DMARDs. All are NICE-listed options, with methotrexate, for severe rheumatoid arthritis inadequately controlled by intensive conventional DMARD therapy. They require individual assessment for infection risk, comorbidity, route, cost and patient preference, but they are not subject to the specific JAK-inhibitor restriction described here. Upadacitinib could be considered later if these suitable biological alternatives were contraindicated, not tolerated or ineffective.

Reference: Janus kinase (JAK) inhibitors: new measures to reduce risks of major cardiovascular events, malignancy, venous thromboembolism, serious infections and increased mortality (26 April 2023) — https://www.gov.uk/drug-safety-update/janus-kinase-jak-inhibitors-new-measures-to-reduce-risks-of-major-cardiovascular-events-malignancy-venous-thromboembolism-serious-infections-and-increased-mortality RINVOQ 15 mg prolonged-release tablets — Summary of Product Characteristics (22 June 2026) — https://www.medicines.org.uk/emc/product/10972/smpc Rheumatoid arthritis in adults: management — Recommendations (Published 11 July 2018; relevant recommendation amended 2024) — https://www.nice.org.uk/guidance/NG100/chapter/recommendations