Background/Purpose: Tofacitinib is an oral Janus kinase inhibitor for the treatment of RA. This study examined response to treatment with tofacitinib 5 mg or 10 mg twice daily (BID) in seropositive (anti-cyclic citrullinated peptide [CCP]+ and/or RF+) versus seronegative (anti-CCP- and RF-) groups of patients with moderately to severely active RA and an inadequate response to disease-modifying antirheumatic drugs.

Methods: ‘Serotype’ subgroups were defined at baseline as: anti-CCP+/RF+ (Sero-1); anti-CCP+/RF- (Sero-2); anti-CCP-/RF+ (Sero-3); anti-CCP-/RF- (Sero-4). Subgroup data were pooled from one monotherapy (ORAL Solo) and four combination therapy (ORAL Sync, Standard, Scan, and Step) Phase 3 studies. The proportions of patients achieving ACR20/50/70, disease activity score in 28 joints (4-variable) using erythrocyte sedimentation rate (DAS28-4[ESR])-associated remission and low disease activity, change from baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI), Short Form (36) (SF-36) physical functioning, and functional assessment of chronic illness therapy (FACIT) were evaluated after 12 weeks. Incidence of adverse events (AEs), discontinuation due to AEs, and serious AEs (SAEs) were compared among subgroups.

Results: In this exploratory analysis, baseline demographics and characteristics were similar between Sero-subgroups 1–4 (n=1551, n=249, n=142, n=449, respectively) for tofacitinib and placebo (PBO; n=670). After 12 weeks of treatment, all Sero-subgroups showed significantly improved ACR20/50/70 response rates with tofacitinib versus PBO (range: p<0.0001–p<0.05). The same range of significance was obtained for Sero-1 and Sero-2 versus PBO in achieving DAS28-4(ESR)<2.6; the lower treatment differences observed in Sero-3 and Sero-4 subgroups were not significant versus PBO. Tofacitinib showed significant (same range) changes in HAQ-DI and FACIT versus PBO for all Sero-subgroups, and SF-36 physical functioning with the exception of Sero-4 subgroup patients receiving tofacitinib 5 mg BID. Frequencies of AEs and SAEs were similar across all treatment groups and Sero‑subgroups. Tofacitinib-treated patients showed similar discontinuation incidence rates (per 100 patient-years) due to AEs in all Sero-subgroups (7.7–13.3 versus PBO: 8.6–19.7).

Conclusion: Tofacitinib treatment significantly reduced the signs and symptoms of RA, irrespective of anti-CCP or RF status. In this analysis, DAS28 remission rates and SF-36 physical functioning appeared to be lower in anti-CCP patients. Similar safety endpoints for tofacitinib treatment were observed across all Sero-subgroups.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/tofacitinib-treatment-outcomes-in-seropositive-versus-seronegative-patients-in-a-phase-3-ra-population/