Comparative effectiveness of antitumour necrosis factor agents, biologics with an alternative mode of action and tofacitinib in an observational cohort of patients with rheumatoid arthritis in Switzerland.

BACKGROUND: Multiple biologic and targeted synthetic disease-modifying rheumatic drugs (b/tsDMARDs) are approved for the management of rheumatoid arthritis (RA), including TNF inhibitors (TNFi), bDMARDs with other modes of action (bDMARD-OMA) and Janus kinase inhibitors (JAKi). Combination of b/tsDMARDs with conventional synthetic DMARDs (csDMARDs) is recommended, yet monotherapy is common in practice. OBJECTIVE: To compare drug maintenance and clinical effectiveness of three alternative treatment options for RA management. METHODS: This observational cohort study was nested within the Swiss RA Registry. TNFi, bDMARD-OMA (abatacept or anti-IL6 agents) or the JAKi tofacitinib (Tofa) initiated in adult RA patients were included. The primary outcome was overall drug retention. We further analysed secondary effectiveness outcomes and whether concomitant csDMARDs modified effectiveness, adjusting for potential confounding factors. RESULTS: 4023 treatment courses of 2600 patients were included, 1862 on TNFi, 1355 on bDMARD-OMA and 806 on Tofa. TNFi was more frequently used as a first b/tsDMARDs, at a younger age and with shorter disease duration. Overall drug maintenance was significantly lower with TNFi compared with Tofa [HR 1.29 (95% CI 1.14 to 1.47)], but similar between bDMARD-OMA and Tofa [HR 1.09 (95% CI 0.96 to 1.24)]. TNFi maintenance was decreased when prescribed without concomitant csDMARDs [HR: 1.27 (95% CI 1.08 to 1.49)], while no difference was observed for bDMARD-OMA or Tofa maintenance with respect to concomitant csDMARDs. CONCLUSION: Tofa drug maintenance was comparable with bDMARDs-OMA and somewhat higher than TNFi. Concomitant csDMARDs appear to be required for optimal effectiveness of TNFi, but not for bDMARD-OMA or Tofa.

Drug retention of biological DMARD in rheumatoid arthritis patients: the role of baseline characteristics and disease evolution.

OBJECTIVE: To examine the association of the evolution in physician-reported and patient-reported outcomes with decision to stop biological DMARDs (bDMARDs) in RA. The contribution of baseline characteristics is well established, but little is known about how the disease evolution influences the decision to discontinue therapy. METHODS: RA patients who initiated a bDMARD treatment from 2009 and with information on date of visit were pooled from seven European RA registers. Each outcome was divided into baseline assessments (capturing the inter-individual differences at drug initiation) and changes from baseline at subsequent visits (capturing the individual evolution). Cox regression models were used to examine their association with drug discontinuation, adjusting for baseline patient and co-therapy characteristics and stratifying by register and calendar year of drug initiation. RESULTS: A total of 25 077 patients initiated a bDMARDs (18 507 a TNF-inhibitor, 3863 tocilizumab and 2707 abatacept) contributing an amount of 46 456.8 patient-years. Overall, drug discontinuation was most strongly associated with a poor evolution of the DAS28, with a hazard ratio of 1.34 (95% CI 1.29, 1.40), followed by its baseline value. A change of Physician Global Assessment was the next strongest predictor of discontinuation, then the Patient Global Assessment. CONCLUSIONS: The decision to discontinue treatments appears to be mostly influenced by DAS28 and particularly its evolution over time, followed by Physician Global Assessment evolution, suggesting that the decision to stop bDMARDs relies more on the physician's than on the patient's global assessment.