Background/Purpose: Tofacitinib is an oral Janus kinase inhibitor for the treatment of RA. This post-hoc analysis investigated the impact of inflammation severity at baseline (BL) – measured by BL CRP levels and ESR – on efficacy and safety of tofacitinib.

Methods: Data were analyzed from studies of tofacitinib in RA patients (pts) with prior inadequate response (IR) to conventional synthetic (cs) or biologic (b) DMARDs, who initiated tofacitinib 5 mg or 10 mg BID as monotherapy or in combination with csDMARDs, mainly methotrexate. Data were pooled from 4 Phase 2 trials (NCT00413660; NCT00550446; NCT00603512; NCT00687193) and 5 Phase 3 randomized, double-blind, placebo-controlled trials (ORAL Scan [NCT00847613]; ORAL Solo [NCT00814307]; ORAL Sync [NCT00856544]; ORAL Standard [NCT00853385]; ORAL Step [NCT00960440]). Analyses were stratified by tertiles, by BL CRP and BL ESR levels, separately. Efficacy variables analyzed at Month (M) 6 included ACR20/50/70 response rates, and changes from BL to M6 in Clinical Disease Activity Index (CDAI), DAS28-4 (ESR), and Simple Disease Activity Index (SDAI). Summary/descriptive statistics were provided. Adverse events (AEs) to M6 were summarized. The results were not adjusted for multiplicity.

Results: The pooled population included 2,161 pts in the csDMARD-IR group and 512 pts in the bDMARD-IR group. Pt characteristics at BL (Table) were generally similar between groups and across CRP and ESR tertiles, except for RA duration. In both dose groups, ACR20/50/70 response rates at M6 were generally numerically higher with higher BL CRP for both csDMARD-IR and bDMARD-IR pts (Figure). Generally, a trend for greater improvement from BL in disease activity at M6 was observed with higher BL CRP but not with higher BL ESR. Proportion of pts with AEs, serious AEs, serious infections, and discontinuations due to AEs to M6 were generally similar regardless of BL CRP or ESR.

Conclusion: While efficacy outcomes in csDMARD-IR and bDMARD-IR RA pts were improved after 6 months’ administration of tofacitinib 5 and 10 mg BID across BL CRP/ESR tertiles, this post-hoc analysis suggests that ACR response rates and disease activity improvements may be numerically greater with higher BL CRP, especially in bDMARD-IR RA pts. Of interest, this was not noted with higher BL ESR. This disproportionate potential predictive value needs further investigation. Analyses investigating the impact of inflammation severity at BL on tofacitinib efficacy in pts with RA are warranted and will include data based on both CRP/ESR tertiles as well as Tender Joint Count (TJC) and Swollen Joint Count (SJC) tertiles.