Assessment of radiographic progression in patients with rheumatoid arthritis treated with tofacitinib in long-term studies

Désirée van der Heijde, Robert B M Landewé, Jürgen Wollenhaupt, Sander Strengholt, Ketti Terry, Kenneth Kwok, Lisy Wang, Stanley Cohen, Désirée van der Heijde, Robert B M Landewé, Jürgen Wollenhaupt, Sander Strengholt, Ketti Terry, Kenneth Kwok, Lisy Wang, Stanley Cohen

Abstract

Objectives: Tofacitinib is an oral Janus kinase inhibitor for the treatment of RA. We evaluated radiographic progression in tofacitinib-treated patients with RA for up to 3 years in two pooled long-term extension (LTE) studies (ORAL Sequel; A3921041) (primary analysis), and for up to 5 years using data integrated from one phase (P)2 (A3921068), two P3 (ORAL Start; ORAL Scan) and two LTE studies (exploratory analysis).

Methods: In LTE studies, patients received tofacitinib 5 mg twice daily (BID) or 10 mg BID as monotherapy or with conventional synthetic (cs)DMARDs. Radiographic outcomes up to 3 years: least squares mean (LSM) change from baseline in van der Heijde modified Total Sharp Score (ΔmTSS), erosion score (ΔES) and joint space narrowing (ΔJSN) score; proportion of patients with no radiographic progression (ΔmTSS ≤0.5); proportion of patients with no new erosions (ΔES ≤0.5). ΔmTSS was evaluated for up to 5 years in an exploratory analysis.

Results: For all tofacitinib-treated patients with radiographic data available at LTE month 36 (n = 414), LSM ΔmTSS was 1.14, LSM ΔES was 0.66, LSM ΔJSN was 0.74, and 74.3% and 86.2% of patients showed no radiographic progression and no new erosions, respectively. Similar values were observed regardless of tofacitinib dose, or whether patients received tofacitinib as monotherapy or with csDMARDs. In an exploratory analysis of integrated P2/P3/LTE studies, LSM ΔmTSS was 3.34 at month 60 (n = 269).

Conclusion: Limited progression of structural damage was observed in tofacitinib-treated patients up to 5 years, with similar results for tofacitinib used as monotherapy or combination therapy up to 3 years.

Trial registration: ClinicalTrials.gov (https://ichgcp.net/clinical-trials-registry/NCT01164579" title="See in ClinicalTrials.gov">NCT01164579; NCT01039688; NCT00847613; NCT00413699; NCT00661661.

Keywords: RA; erosion; joint space narrowing; modified Total Sharp Score; progression; radiograph; tofacitinib.

© The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Rheumatology.

Figures

Fig . 1
Fig. 1
Change from baseline in mTSS at month 36 All analyses were based on observed cases. Horizontal reference line represents ΔmTSS equal to 0.5. Δ: change from baseline; BID: twice daily; csDMARDs: conventional synthetic DMARDs; mTSS: modified Total Sharp Score; n: number of patients with baseline and at least one post-baseline radiographic assessments.
Fig . 2
Fig. 2
Least squares mean change from baseline in radiographic assessments over 36 months All analyses were based on observed cases using MMRM. BID: twice daily; csDMARDs: conventional synthetic DMARDs; LSM: least squares mean; MMRM: mixed-effect model with repeated measures; mTSS: modified Total Sharp Score.
Fig . 3
Fig. 3
Percentage of patients with no radiographic progression or no new erosions All analyses were based on observed cases. BID: twice daily; csDMARDs: conventional synthetic DMARDs.

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Source: PubMed

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