Nagy et al. propose a unifying and holistic framework for understanding and addressing the concept of difficult-to-treat (D2T) disease across rheumatology, integrating cross-disciplinary evidence and recommending its incorporation into future disease management strategies. The D2T state requires a comprehensive, holistic, multidisciplinary approach that considers the specific characteristics of each disease and the personalised needs of the patient.

Di Napoli et al. conducted a global pharmacovigilance analysis comparing MACE between JAKis and anti-TNFα therapies in patients with RA. JAKis were more frequently associated with reported MACE, particularly stroke, and had a shorter median time to onset than
anti-TNFα therapy.

Eberhard et al. investigated the effectiveness of JAKi versus bDMARDs on pain reduction in RA patients, using Swedish national register data. JAKi treatment resulted in a significantly greater reduction in pain at three months compared with TNFis, with a higher proportion achieving low pain at 12 months, particularly in those previously treated with multiple bDMARDs.

Zhao et al. found that among patients with PsA or axSpA, JAKi were not associated with increased risk of CVD or common cancers compared to TNFi or IL-17i.

Deodhar et al. conducted a pooled analysis of Phase 2 and 3 RCT data to assess the safety of tofacitinib in AS. The results showed that tofacitinib 5 mg BID had a tolerable safety profile over 48 weeks, consistent with its use in other inflammatory conditions such as RA and PsA.

Haraoui et al. conducted a subgroup analysis of the CANTORAL study, showing that tofacitinib effectiveness was similar in patients with or without CV risk enrichment. However, AEs, particularly in older patients (≥65 years), were more frequent in the CV+ cohort. These findings highlight the need for tailored CV risk management when treating RA with tofacitinib.

Edwards et al. report on real-world data for baricitinib monotherapy in rheumatoid arthritis, showing significant disease activity reduction across multiple registries and observational studies. These findings reinforce the viability of baricitinib monotherapy in clinical practice for RA patients, complementing existing guidelines.

Adami et al. conducted a retrospective analysis to evaluate the GC sparing effects of JAKi versus bDMARDs in rheumatoid arthritis patients. They found that JAKi therapy was associated with a significant reduction in GC dose compared with bDMARDs. This suggests that JAKi could be more effective in reducing long-term GC exposure in RA patients.