Background: Clinical trials in selected rheumatoid arthritis (RA) patient populations have shown possible benefits for Tumor Necrosis Factor inhibitors (TNFi’s) and Janus kinase inhibitors (JAKi’s) used in combination with csDMARDs over monotherapy. However, it remains to be determined whether these results can be generalized to daily practice populations, including different RA subgroups.

Objectives: To compare real-world effectiveness of tofacitinib monotherapy to adalimumab monotherapy, tofacitinib, and adalimumab in combination with csDMARDs in RA subgroups, with respect to ACPA status and age.

Methods: Retrospective routine care data was used from six Dutch cohorts for RA-patients who initiated tofacitinib or adalimumab between 2000-2022. Drug survival of tofacitinib monotherapy (n=229) was compared with that of tofacitinib combination therapy (n=180), adalimumab monotherapy (n=1018) and adalimumab combination therapy (n=1361) using Kaplan-Meijer curves and Cox regression models. With generalized linear mixed models, the association between treatment and change in DAS28 after six and twelve months was evaluated compared to baseline, including multivariate adjustment to attempt to account for confounding by indication, including timing of treatment and previous b/tsDMARD use. Effect modifications of ACPA and age at treatment onset were tested for both models.

Results: Patients who started tofacitinib monotherapy were older compared to other treatment groups (tofacitinib monotherapy vs tofacitinib combination therapy, adalimumab mono- and combination therapy: 61 vs 55, 58 and 58 years, p<0.001) and had used previous b/tsDMARDs more often compared to the adalimumab treatment groups (36% of patients in the tofacitinib mono group vs 41% (tofacitinib combi group), 19% (adalimumab mono group) and 13% (adalimumab combi group)). There were no significant differences between treatment groups regarding the baseline characteristics sex and current/ever smokers. The proportion of patients who were ACPA and RF positive was: 56% and 33%, 50% and 38%, 44% and 47%, 51% and 54%, in the tofacitinib mono group, tofacitinib combi group, adalimumab mono- and combi group respectively. Compared to tofacitinib monotherapy, in adjusted analyses, the risk of drug failure was similar for tofacitinib combination therapy (aHR 1.21, 95% CI: 0.96-1.53), but lower for adalimumab mono- (aHR 0.77, 95% CI: 0.63-0.94) and combination therapy (aHR 0.69, 95% CI: 0.57-0.85) (Figure 1). DAS28 improved more with adalimumab treatment than with tofacitinib monotherapy (at six months adjusted change in DAS28 for tofacitinib monotherapy β -0.01 per month (95% CI: -0.097;0.078, p>0.1), tofacitinib combination therapy β 0.004 (95% CI: -0.08;0.09, p>0.1), adalimumab monotherapy β -0.07 (95% CI: -0.095;-0.038, p<0.05) and adalimumab combination therapy β -0.071 (95% CI: -0.096;-0.046, p<0.05). Older age was associated with significantly lower drug survival and change in DAS28 over time (Table 1). No effect modification by ACPA was observed (p>0.10).

Conclusion: Based on real-world data from six longitudinal Dutch cohorts, drug survival and improvement in DAS28 were less for tofacitinib than for adalimumab, with similar outcomes with or without co treatment with csDMARDs. Older patients had lower drug survival independently of treatment group. ACPA status was not related to treatment effectiveness. Although results were adjusted for potential confounders, residual (unmeasured) confounders may have influenced these outcomes.

REFERENCES: NIL.

• Download figure
• Open in new tab
• Download powerpoint

• Download figure
• Open in new tab
• Download powerpoint

Acknowledgements: NIL.

Disclosure of Interests: Isabell Nevins: None declared, A.A. den Broeder Grants for research and quality of care projects to the institution from Lilly, Abbvie, Galapagos, Novartis, Pfizer, Gilead, Sanofi, Biogen, Celltrion., Pauline S.M. Groenen: None declared, Petronella D.M. de Buck: None declared, Floor Reimann: None declared, Reinhard Bos: None declared, Wiepke Drossaers-Bakker: None declared, Mirjam Hegeman: None declared, Hans van Groenendael: None declared, Herman Kasper Glas: None declared, Tom Huizinga: None declared, Cornelia F. Allaart: None declared, Sytske Anne Bergstra Speaker fees from Benecke, ASPIRE grant from Pfizer. This abstract was sponsored by an ASPIRE grant from Pfizer. Analyses and reporting were conducted independently of the sponsor.