Effect of Discontinuation or Initiation of Methotrexate or Glucocorticoids on Tofacitinib Efficacy in Patients with Rheumatoid Arthritis: A Post Hoc Analysis

Abstract

Introduction: Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). We evaluated the effect of concomitant methotrexate (MTX) or glucocorticoid (GC) use on tofacitinib clinical efficacy.

Methods: Data were pooled from two open-label, long-term extension studies of tofacitinib 5 or 10 mg twice daily in patients with RA. Response according to Clinical Disease Activity Index (CDAI) was assessed separately in patients who discontinued (no MTX/GC use within 30 days prior to year-3 visit; assessment at month 3/year 3) or initiated (on/before year 3; assessment at initiation and year 3) MTX/GC.

Results: By year 3, among patients receiving background MTX at baseline, 186/1608 (11.6%) discontinued MTX, and 319/1434 (22.2%) patients receiving GC at baseline discontinued GC. Overall, 70.4/69.1% of patients who discontinued/continued MTX and 72.7/65.9% who discontinued/continued GC achieved CDAI remission or low disease activity (LDA) at year 3. Month 3 remission/LDA rates were maintained at year 3 in the majority of patients, irrespective of MTX/GC discontinuation/continuation. By year 3, 6.2% of patients receiving tofacitinib without MTX at baseline had initiated concomitant MTX, and 25.1% receiving tofacitinib without GC initiated GC; 69.0% and 45.4% initiating MTX or GC, respectively, had a CDAI-defined incomplete response prior to initiation. RA signs/symptoms improved following MTX initiation; only modest improvement was observed with GC initiation.

Conclusions: Patients achieving remission/LDA with tofacitinib may discontinue MTX or GC and maintain treatment response. Patients with an incomplete response may benefit from adding concomitant MTX.

Funding: Pfizer Inc.

Trial registration: Study A3921024 [NCT00413699] and Study A3921041 [NCT00661661].

Keywords: Glucocorticoid; Long-term; Methotrexate; Rheumatoid arthritis; Tofacitinib.

Figures

Fig. 1

a CDAI response at year 3 in patients who were receiving tofacitinib with background MTX at baseline and subsequently discontinued or continued MTX; b maintenance of month-3 CDAI response at year 3 among patients who were receiving tofacitinib with background MTX at baseline and at the month-3 visit, who discontinued or continued MTX prior to the year-3 visit; c CDAI response at the last post-baseline visit prior to and following initiation of MTX at year 3 among patients who were receiving tofacitinib without MTX at baseline and subsequently initiated MTX. CDAI remission: ≤ 2.8; CDAI LDA: CDAI > 2.8 to ≤ 10; CDAI incomplete response as CDAI > 10. Year-3 data were missing from one patient who discontinued MTX, two patients who continued MTX, and one patient after initiation of MTX. CDAI Clinical Disease Activity Index, LDA low disease activity, MTX methotrexate

Fig. 2

a CDAI response at year 3 in patients who were receiving tofacitinib with GC at baseline and subsequently discontinued or continued GC; b maintenance of month-3 CDAI response at year 3 among patients who were receiving tofacitinib with GC at baseline and at the month 3 visit, who discontinued or continued GC prior to the year-3 visit; c CDAI response at the last post-baseline visit prior to and following initiation of GC at year 3 among patients who were receiving tofacitinib without GC at baseline and subsequently initiated GC. CDAI remission: ≤ 2.8; CDAI LDA: CDAI > 2.8 to ≤ 10; CDAI incomplete response as CDAI > 10. Year-3 data were missing from one patient who discontinued GC, two patients who continued GC, four patients prior to initiation of GC, and three patients after initiation of GC. CDAI Clinical Disease Activity Index, GC glucocorticoid, LDA low disease activity