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Upadacitinib vs Baricitinib — SCE Rheumatology MCQ

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ModerateRheumatology PharmacologyUpadacitinib vs BaricitinibSCE Rheumatology

A 50-year-old woman with rheumatoid arthritis asks how the oral targeted synthetic DMARDs upadacitinib and baricitinib differ pharmacologically. Which statement best describes their JAK isoform selectivity?

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Correct answer: BUpadacitinib preferentially inhibits JAK1-dependent signalling, whereas baricitinib inhibits JAK1 and JAK2 with similar biochemical potency.

Upadacitinib is a selective, reversible JAK inhibitor that preferentially inhibits JAK1- or JAK1/3-dependent signalling, with functional selectivity over receptors signalling through paired JAK2. Baricitinib inhibits JAK1 and JAK2; its isolated-enzyme IC50 values for these isoforms are similar. Therefore, C is the best comparison. The other options assign incorrect preferences for JAK2, JAK3 or TYK2, or incorrectly imply equivalent selectivity. Selectivity is assay- and exposure-dependent and must not be assumed to confer a proven clinical safety advantage: UK MHRA risk-minimisation advice concerning serious infection, malignancy, major adverse cardiovascular events, venous thromboembolism and mortality applies across the inflammatory-disease JAK-inhibitor class.

Reference: Electronic Medicines Compendium. RINVOQ SmPC, section 5.1, updated 2026, https://www.medicines.org.uk/emc/product/10972/smpc; Baricitinib Lilly SmPC, section 5.1, updated 2026, https://www.medicines.org.uk/emc/product/16006/smpc