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

Fleischmann, Roy; Wollenhaupt, J.; Cohen, Stanley; Wang, Lisy; Fan, Huiying; Bandi, Vara; Andrews, John S.; Takiya, Liza; Bananis, Eustratios; Weinblatt, Michael E.

doi:10.1007/s40744-018-0093-7

Cited by 13 publications

(10 citation statements)

References 28 publications

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“…In biologic-naïve patients with active RA and an inadequate response to MTX who received abatacept or adalimumab, whether patients remained on stable GCs (≤10 mg/day) started prior to baseline, or were not treated with GC during the study, had no detectable impact on clinical, functional or radiographic outcomes over two years. This confirms results of other reports with the same outcomes in the context of tofacitinib, tocilizumab, adalimumab and rituximab treatments [10][11][12][13][15][16][17][18]. In our current study (i) we showed similar results with a different bDMARD, i.e., abatacept, and (ii) we confirmed previous findings about adalimumab.…”

Section: Discussionsupporting

confidence: 92%

“…Biological (bDMARDs) or targeted synthetic DMARDs (tsDMARDs) randomized controlled trials providing published data about the impact of background GC therapy on clinical and radiological outcomes in RA, are scarce [ 10 , 11 , 12 , 13 ]. The objective of this post hoc analysis of the AMPLE trial was to assess whether there was an impact of background GCs at doses of ≤10 mg/day (prednisone equivalent) on the efficacy and safety of SC abatacept or SC adalimumab in biologic-naïve patients with active RA and an inadequate response to MTX.…”

Section: Introductionmentioning

confidence: 99%

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Background Glucocorticoid Therapy Has No Impact on Efficacy and Safety of Abatacept or Adalimumab in Patients with Rheumatoid Arthritis

Degboé

Schiff

Weinblatt

et al. 2020

JCM

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To date, the impact of background glucocorticoids (GC) on the efficacy and safety of abatacept or adalimumab in patients with active rheumatoid arthritis (RA) is not clearly established. This post hoc analysis of (AMPLE) trial (NCT00929864) compared efficacy and safety outcomes over 2 years in patients treated with abatacept or adalimumab plus background methotrexate (MTX), who continued GC (≤10 mg/day) versus those who were not receiving GC (no-GC). Of 646 randomized patients, 317 received abatacept + MTX (161 GC, 156 no-GC) and 326 received adalimumab + MTX (162 GC, 164 no-GC). At Year 2, the adjusted mean changes from baseline in Disease Activity Score (DAS28 C-reactive protein (CRP)) and Health Assessment Questionnaire-Disability Index (HAQ-DI) were not significantly different in the GC versus no-GC subgroups receiving abatacept or adalimumab. A similar proportion of patients achieved remission, HAQ-DI score improvement ≥0.3 and radiographic progression rates. No clinically meaningful safety differences were observed between GC versus no-GC subgroups either with abatacept or adalimumab. In patients with active RA of similar baseline disease activity treated with abatacept or adalimumab plus background MTX, there was no additional value of background GC on clinical, functional or radiographic outcomes over two years.

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Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Background Glucocorticoid Therapy Has No Impact on Efficacy and Safety of Abatacept or Adalimumab in Patients with Rheumatoid Arthritis

Degboé

Schiff

Weinblatt

et al. 2020

JCM

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“…2 7 Previous clinical investigations have evaluated the feasibility of GC discontinuation by introducing the bDMARD or tofacitinib. [27][28][29][30][31][32] For example, Inoue et al analysed 80 patients with RA taking a median PSL dose of 5.0 (1.0-10.0) mg/day at bDMARDs initiation. 31 Over a median follow-up of 33.1 months, 31.3% of participants discontinued GC.…”

Section: Discussionmentioning

confidence: 99%

Dynamical trajectory of glucocorticoids tapering and discontinuation in patients with rheumatoid arthritis commencing glucocorticoids with csDMARDs: a real-world data from 2009 to 2020

Xie

Hao

et al. 2021

Ann Rheum Dis

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ObjectiveTo unravel the dynamical trajectory and features of glucocorticoids (GC) tapering and discontinuation in patients with rheumatoid arthritis (RA) commencing GC with concomitant conventional synthetic disease-modifying antirheumatic drugs (csDMARDs).MethodsWe used data from longitudinal real-world Treat-to-TARget in RA cohort. Patients with RA who started GC and contaminant csDMARDs therapy were included. The changes in GC dose and disease activity were evaluated. GC discontinuation rate was analysed using Kaplan-Meier analysis. The relapse profile within 6 months after GC discontinuation was also analysed.ResultsA total of 207 patients with RA were included. During a median follow-up of 38.6 months, 124 patients discontinued GC. The median prednisolone dose of 10 (5–10) mg/day at initiation was reduced by 50% in the first 6 months and then more slowly, to zero by 48 months eventually. The cumulative probabilities of GC discontinuation were 9.7%, 26.6%, 48.0% and 58.6% at month 6, years 1, 2 and 3, with calculated median time to GC cessation of 27 months. In 110 DMARD-naïve patients, the corresponding cumulative probabilities of GC discontinuation were, respectively, 12.7%, 30.0%, 50.9% and 60.6%, with calculated median time to GC cessation of 24 months. Of the 124 patients who discontinued GC, adding other csDMARDs or concomitant csDMARDs increment was documented in 28.2% of them. Approximately half of 124 patients were in clinical remission at GC discontinuation. Within 6 months after GC withdrawal, 79.1% (91/115) of patients maintained relapse free.ConclusionsIn patients with RA commencing GC besides csDMARDs, GC is feasibly discontinued with favourable control of disease activity in real-life setting, mostly without short-term flare. But the withdrawal time is far from reaching the recommended time frame, indicating the gap between real-world practice and current guidelines.

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“…Patients were further classified into subgroups of patients who stayed on tofacitinib monotherapy or stayed on tofacitinib combination therapy with background csDMARDs (ie, patients remained on their study‐start therapy for the entire study duration, with the exception of a 28‐day or less break in csDMARD use allowed for stay‐on‐csDMARD patients) . Patients who changed their initial background csDMARD therapy were not included in these analyses; however, their data are included in the “All tofacitinib” cohort.…”

Section: Methodsmentioning

confidence: 99%

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

Pope

Keystone

Jamal

et al. 2019

ACR Open Rheumatology

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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.

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

Cited by 13 publications

References 28 publications

Background Glucocorticoid Therapy Has No Impact on Efficacy and Safety of Abatacept or Adalimumab in Patients with Rheumatoid Arthritis

Background Glucocorticoid Therapy Has No Impact on Efficacy and Safety of Abatacept or Adalimumab in Patients with Rheumatoid Arthritis

Dynamical trajectory of glucocorticoids tapering and discontinuation in patients with rheumatoid arthritis commencing glucocorticoids with csDMARDs: a real-world data from 2009 to 2020

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

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