THU0185 Comparison of tofacitinib safety and efficacy in rheumatoid arthritis patients with inadequate response to conventional synthetic dmards, or to one or more biological dmards

Abstract

BackgroundTofacitinib is an oral JAK inhibitor for the treatment (tx) of rheumatoid arthritis (RA). Studies have shown diminishing response to tx in RA patients (pts) when cycling through TNF inhibitors. Prior analyses assessed tofacitinib in csDMARD-inadequate response (IR) pts vs overall bDMARD-IR pts.ObjectivesTo compare tofacitinib safety and efficacy in RA pts who have previously failed tx (lack of efficacy and/or safety reasons) with csDMARDs, with pts who failed tx with either 1 or ≥2 prior bDMARDs.MethodsData from pts who received ≥1 dose of tofacitinib in 19 RA studies up to 96 months (2 Phase [P] 1; 9 P2; 6 P3; 2 LTE studies [1 LTE ongoing; data as of March 2015]) were used in this analysis. Data were pooled across all 19 studies for safety assessments in the All RA population: csDMARD-IR, n=4377; bDMARD-IR, n=838 (1 bDMARD-IR, n=533; ≥2 bDMARD-IR n=305). Safety was also assessed up to 24 months in pts randomised to tofacitinib 5 or 10 mg BID or placebo (PBO) in a pooled P2/P3 randomised controlled trial (RCT) population (8 P2, 6 P3 studies; csDMARD-IR, n=3328; bDMARD-IR, n=782). Incidence rates (pts with events/100 pt-years) were calculated for serious AEs (SAEs), serious infections (SIs) and herpes zoster (HZ). Efficacy was assessed by pts achieving ACR20 response and DAS28-4(ESR) ≤3.2 at Month 3 in a pooled P3 RCT population (csDMARD-IR, n=2375; bDMARD-IR, n=664).ResultsPrior to tofacitinib tx, bDMARD-IR pts had longer RA duration, greater disease burden and more corticosteroid use vs csDMARD-IR pts. SAEs were more common among bDMARD-IR vs csDMARD-IR pts in both the P2/P3 RCT and the All RA populations; SAE rates were not higher in pts failing ≥2 bDMARDs vs 1 bDMARD (Table). Incidence rates for SIs were generally greater in pts with IR to bDMARDs vs csDMARDs in the All RA population, but generally lower in pts with IR to 1 or ≥2 bDMARDs vs csDMARDs in the P2/P3 RCT population; incidence with 5 mg BID was lower for 1 vs ≥2 bDMARDs in the P2/P3 RCT population. Incidence rates for HZ were similar between pts with IR to csDMARDs or 1 bDMARD, but appeared numerically greater in pts with IR to ≥2 bDMARDs in both the P2/P3 RCT and the All RA populations. A similar pattern was observed across tofacitinib and PBO groups. Efficacy at Month 3 in the P3 RCT population was greater with both tofacitinib doses vs PBO. Although absolute response was smaller in pts with IR to bDMARDs vs csDMARDs, generally similar efficacy was observed in pts with IR to 1 or ≥2 bDMARDs (Table).ConclusionsSAEs and SIEs were more common in tofacitinib- and PBO-treated pts with IR to bDMARDs vs csDMARDs; increased risk was generally not observed with increasing number of prior bDMARDs. HZ risk appeared greater with ≥2 bDMARDs vs 1 bDMARD. Efficacy was greater with tofacitinib vs PBO for csDMARD-IR and bDMARD-IR pts, with similar response observed in pts with IR to ≥2 or 1 bDMARD. These data support the use of tofacitinib in different lines of therapy, although the analysis is limited by smaller sample size in some groups.Acknowledgement...

Tofacitinib in the treatment of Indian patients with rheumatoid arthritis: A post hoc analysis of efficacy and safety in Phase 3 and long‐term extension studies over 7 years

“…These differences may partially explain the comparatively lower proportion of Indian patients with AEs and SAEs, compared with the ROW population, as there is evidence that the risk of some AEs is increased by the use of RA treatments, [49][50][51][52] and the risk of some AEs has also been shown to differ in csDMARD-IR vs bDMARD-IR patients receiving tofacitinib. 53 However, conversely, rates of AESI were similar in both populations, despite Indian patients being younger, having no prior bDMARD experience, shorter disease duration, and higher baseline disease activity, compared with the ROW population. It is also possible that there were differences in undertreatment or delayed treatment between the two populations, which may confound interpretation of these results.…”

“…In the safety analysis, more Indian patients were from the ORAL Start study and were MTX‐naïve, compared with ROW patients, and all Indian patients were bDMARD‐naïve, whereas the ROW population included TNFi‐inadequate responders from ORAL Step. These differences may partially explain the comparatively lower proportion of Indian patients with AEs and SAEs, compared with the ROW population, as there is evidence that the risk of some AEs is increased by the use of RA treatments, 49‐52 and the risk of some AEs has also been shown to differ in csDMARD‐IR vs bDMARD‐IR patients receiving tofacitinib 53 . However, conversely, rates of AESI were similar in both populations, despite Indian patients being younger, having no prior bDMARD experience, shorter disease duration, and higher baseline disease activity, compared with the ROW population.…”

Pharmacological and non-pharmacological therapeutic strategies in difficult-to-treat rheumatoid arthritis: a systematic literature review informing the EULAR recommendations for the management of difficult-to-treat rheumatoid arthritis

“…Additionally, the studies on tofacitinib, upadacitinib and filgotinib enrolled patients who failed different bDMARDs and not only TNFis. 57 80 120 Nevertheless, future studies should assess to what extent this tendency is related to these specific b/tsDMARDs or to the order of their application in therapeutic strategies. Furthermore, a tendency was found for non-TNFi bDMARDs to be more effective than TNFis in patients who failed at least one TNFi, although insufficient evidence was identified to prioritise different non-TNFi b/tsDMARDs.…”