Persistence of Tofacitinib in the Treatment of Rheumatoid Arthritis in Open‐Label, Long‐Term Extension Studies up to 9.5 Years

Abstract

ObjectiveTofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). This post hoc analysis evaluated tofacitinib persistence in patients with RA in long‐term extension (LTE) studies up to 9.5 years.MethodsData were pooled from two LTE studies: ORAL Sequel (NCT00413699) and Study A3921041 (NCT00661661). Patients received tofacitinib 5 or 10 mg twice daily (BID), as monotherapy or with background conventional synthetic disease‐modifying antirheumatic drugs. Kaplan‐Meier estimates for tofacitinib drug survival and reasons for discontinuation were evaluated. Baseline factors were analyzed as predictors of persistence.ResultsIn 4967 tofacitinib‐treated patients entering LTE studies, mean (maximum) treatment duration was 3.5 (9.4) years. Median drug survival (95% confidence interval) was 4.9 (4.7, 5.1) years. Estimated 2‐ and 5‐year drug survival rates were 75.5% and 49.4%, respectively. Median drug survival was similar between the tofacitinib 5 and 10 mg BID groups, and slightly higher for patients receiving tofacitinib monotherapy versus combination therapy. Overall, 50.7% of patients discontinued tofacitinib; of these, 47.2% were due to adverse events and 7.1% for lack/loss of efficacy. An increased risk of discontinuation was associated with baseline diabetes, hypertension, negative anticyclic citrullinated peptide (anti‐CCP), negative rheumatoid factor (RF), and inadequate response to tumor necrosis factor inhibitors (TNFi‐IR).ConclusionMedian drug survival of tofacitinib‐treated patients participating in LTE studies was approximately 5 years and was similar for tofacitinib dosed at 5 and 10 mg BID. Reduced drug survival was associated with negative anti‐CCP/RF status, TNFi‐IR, and certain comorbidities. These data support tofacitinib use for long‐term management of RA.

Strategies toward rheumatoid arthritis therapy; the old and the new

“…Studies have demonstrated that the JAK inhibitors are almost identical to other biological agents in adverse events. However, tofacitinib has been associated with increased susceptibility to herpes zoster infection (Cohen et al, 2017;Curtis, Xie, Yun, Bernatsky, & Winthrop, 2016;J. Pope et al, 2017;Yamaoka, 2016a).…”

Comment on: “Retrospective Claims Analysis Indirectly Comparing Medication Adherence and Persistence Between Intravenous Biologics and Oral Small-Molecule Therapies in Inflammatory Bowel Diseases”

“…Using mutually exclusive IBD and RA infliximab treatment data to bridge differences across the unique inflammatory diseases, the authors conclude that, after adjustment, adherence was higher with infusions than oral medications [1]. These results are in contrast to findings from previous well-conducted studies [2,3]. Furthermore, the analysis by Moran et al does not take into account a number of important factors, and we suggest relies on questionable methodology.…”

“…Finally, published data on the concept of persistence and adherence with tofacitinib have demonstrated 2-and 5-year estimated drug survival rates of 75.5% and 49.4%, respectively, in a clinical trial setting [2], while real-world data comparing tofacitinib with common biologics (adalimumab, etanercept, and abatacept) for the treatment of RA reported persistence, and adherence of tofacitinib was at least comparable to that of the biologics [3].…”

Response to “Comment on Retrospective Claims Analysis Indirectly Comparing Medication Adherence and Persistence Between Intravenous Biologics and Oral Small-Molecule Therapies in Inflammatory Bowel Diseases”

“…In the Comment letter, the authors state ''the authors conclude that after adjustment, adherence was higher with infusions than oral medications [1]. These results are in contrast to findings from previous well-conducted studies [2,3].'' We disagree that the two studies cited by the Comment authors provide evidence that adherence is higher with oral medications than with infusions.…”