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SAT0149 Radiographic Outcomes in Patients Achieving Clinical Remission or Low Disease Activity in A Phase 3 Study of Sarilumab plus Methotrexate in Patients with Active, Moderate-To-Severe Rheumatoid Arthritis
  1. D. van der Heijde1,
  2. J. Simon2,
  3. H. van Hoogstraten3,
  4. E.K. Mangan4,
  5. J. Fay4,
  6. J. van Adelsberg4,
  7. C. Fan3,
  8. M.C. Genovese5
  1. 1Leiden University Medical Centre, Leiden, Netherlands
  2. 2Köhler & Milstein Research, Yucatan, Mexico
  3. 3Sanofi, Bridgewater
  4. 4Regeneron Pharmaceuticals, Inc., Tarrytown
  5. 5Stanford University Medical Center, Palo Alto, United States

Abstract

Background Clinical remission is an important treatment target of rheumatoid arthritis (RA), and it is important to understand its role as a surrogate for radiographic inhibition.1,2 In the phase 3 MOBILITY study (NCT01061736), sarilumab (150 or 200 mg subcutaneously every 2 wks [q2w] + methotrexate [MTX]) demonstrated clinical and radiographic efficacy in adults with active, moderate-to-severe RA with inadequate response to MTX.3 The most common treatment-emergent adverse events were infections, neutropenia, injection site reactions, and increased transaminases.

Objectives The objective of this post hoc analysis was to examine differences in radiographic progression between patients in MOBILITY who did and those who did not achieve different definitions for remission or low disease activity (LDA).

Methods Remission and LDA categories included CDAI ≤2.8 and ≤10, SDAI ≤3.3 and ≤11, and Boolean-based ACR/EULAR remission, which included tender joint count and swollen joint count (28-joint count) ≤1, CRP ≤10 mg/L, and patient global visual analog scale ≤10. Cutoffs for 28-joint disease activity score by C-reactive protein (DAS28-CRP) were <2.6 and ≤3.2. Differences in radiographic progression, defined as the mean change from baseline in modified total Sharp score (mTSS), between the treatment and placebo groups in these benchmarks were assessed using a 2-sided Cochran-Mantel-Haenszel test stratified by prior biologic use and region. Missing or postrescue radiographic data were imputed by a linear extrapolation approach for any patient with ≥1 postbaseline radiograph, but these patients were not counted as in remission or with LDA for clinical outcomes.

Results Overall, a greater proportion of patients receiving either dose of sarilumab + MTX achieved remission or LDA and had significantly less radiographic progression than patients receiving placebo + MTX (Table). Regardless of treatment group, patients who achieved remission or LDA showed less radiographic progression at wk 52 than patients who did not (Table). In general, the progression in patients achieving remission was lower than in patients achieving LDA. Even if patients did not achieve remission or LDA, patients receiving sarilumab + MTX had less radiographic progression than those receiving placebo + MTX. Smaller mean changes in mTSS were observed with sarilumab 200 mg q2w compared with sarilumab 150 mg q2w. Similar findings were observed for erosion score and joint space narrowing.

Conclusions Remission or LDA was associated with less radiographic progression irrespective of treatment, and remission was associated with less radiographic progression than LDA. Irrespective of whether patients achieved remission or LDA, sarilumab + MTX was associated with less radiographic progression than placebo + MTX.

  1. Smolen et al. Ann Rheum Dis. 2014;73:492–509

  2. Radner et al. Arthritis Res Ther. 2014;16:R56

  3. Genovese et al. Arthritis Rheumatol. 2015;67:1424–1437

Acknowledgement This study was sponsored by Sanofi and Regeneron Pharmaceuticals, Inc. Editorial assistance was provided by Todd Parker, PhD, MedThink SciCom, and funded by Sanofi and Regeneron Pharmaceuticals, Inc.

Disclosure of Interest D. van der Heijde Consultant for: Sanofi, J. Simon: None declared, H. van Hoogstraten Shareholder of: Sanofi, Employee of: Sanofi, E. Mangan Shareholder of: Regeneron Pharmaceuticals, Inc, Employee of: Regeneron Pharmaceuticals, Inc, J. Fay Shareholder of: Regeneron Pharmaceuticals, Inc, Employee of: Regeneron Pharmaceuticals, Inc, J. van Adelsberg Shareholder of: Regeneron Pharmaceuticals, Inc, Employee of: Regeneron Pharmaceuticals, Inc, C. Fan Shareholder of: Sanofi, Employee of: Sanofi, M. Genovese Grant/research support from: Roche, Sanofi, GSK, R-Pharma, RuiYi, and BMS, Consultant for: Roche, Sanofi, GSK, R-Pharma, RuiYi, and BMS

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