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POS0651 (2021)
CLINICAL AND FUNCTIONAL RESPONSE TO TOFACITINIB IN PATIENTS WITH RHEUMATOID ARTHRITIS: PROBABILITY PLOT ANALYSIS OF RESULTS FROM A 48-WEEK PHASE 3b/4 METHOTREXATE WITHDRAWAL STUDY
S. B. Cohen1, Y. H. Chen2, N. Sugiyama3, J. L. Rivas4, A. Diehl5, T. Lukic6, J. Paulissen6, H. Fan5, T. Hirose3, E. Keystone7
1Metroplex Clinical Research Center, Dallas, TX, United States of America
2Taichung Veterans General Hospital, Division of Allergy, Immunology, and Rheumatology, Taichung, Taiwan, Republic of China
3Pfizer Japan Inc, Inflammation and Immunology, Tokyo, Japan
4Pfizer SLU, Inflammation and Immunology, Madrid, Spain
5Pfizer Inc, Inflammation and Immunology, Collegeville, PA, United States of America
6Pfizer Inc, Inflammation and Immunology, New York, NY, United States of America
7Mount Sinai Hospital, Toronto, ON, Canada

Background: The Phase 3b/4 study ORAL Shift (NCT02831855) demonstrated sustained efficacy/safety of tofacitinib modified-release 11 mg QD following MTX withdrawal, that was non-inferior to continued tofacitinib + MTX use, in patients (pts) with moderate to severe RA who achieved LDA with tofacitinib + MTX at Week (W)24. 1


Objectives: To assess differences and similarities in clinical/functional responses in pts receiving tofacitinib ± MTX in ORAL Shift.


Methods: In ORAL Shift, pts received open-label tofacitinib + MTX to W24; at W24, pts who achieved CDAI LDA were randomised to receive tofacitinib + MTX or tofacitinib + placebo (PBO) from W24–48. In this post hoc analysis, clinical efficacy endpoints were ACR-N (minimum % change from baseline [BL; Δ] at W48 achieved by each pt in 3 efficacy measures), ΔDAS28-4(ESR), and DAS28-4(ESR) remission/LDA (scores ≤3.2) and moderate/high disease activity (scores >3.2). Functional efficacy endpoints were ΔHAQ-DI and HAQ-DI clinically relevant functional progression (CRFP) status at W48, defined as failure to achieve improvement in HAQ-DI ≥ minimum clinically important difference (MCID; ≥0.22 decrease from BL in HAQ-DI). Thus, CRFP was defined as <0.22 decrease, no change or increase from BL in HAQ-DI at W48. All efficacy endpoints were summarised descriptively. Cumulative probability plots of ACR-N and ΔHAQ-DI were produced. Median of mean CRP values from BL–W24 and >W24–48 were assessed by response subgroups.


Results: 266 pts receiving tofacitinib + MTX and 264 pts receiving tofacitinib + PBO in W24–48 were included. At W48: mean ACR-N was numerically greater with tofacitinib + MTX vs tofacitinib + PBO (60.8 vs 53.1); mean decrease in HAQ-DI was generally similar between groups (-0.71 vs -0.67); mean decrease in DAS28-4(ESR) was numerically greater with tofacitinib + MTX vs tofacitinib + PBO (-2.95 vs -2.68). The differences/similarities between groups in ACR-N and ΔHAQ-DI were also seen in cumulative probability plots ( Figure 1 ). CRFP rates were numerically lower with tofacitinib + MTX (18.7%) vs tofacitinib + PBO (23.5%), and in pts with remission/LDA (tofacitinib + MTX, 12.1%; tofacitinib + PBO, 16.8%) vs moderate/high disease activity (tofacitinib + MTX, 26.2%; tofacitinib + PBO, 30.8%). Median of mean CRP over time was generally numerically lower in pts with CRFP vs non-CRFP and DAS28-4(ESR)-defined remission/LDA vs moderate/high disease activity; and in those receiving tofacitinib + PBO vs tofacitinib + MTX, irrespective of CRFP or DAS28-4(ESR) disease status ( Table 1 ).

Median of mean CRP a up to W48 by response subgroups

Tofacitinib 11 mg QD + MTX Tofacitinib 11 mg QD + PBO
Mean CRP, a median (IQR) [n] >BL–W24 >W24–48 >BL–W24 >W24–48
HAQ-DI CRFP 2.84 (1.15–7.30) 2.30 (0.82–4.75) 1.45 (0.77–4.42) 2.28 (0.53–7.28)
[45] [46] [56] [56]
HAQ-DI non-CRFP 2.81 (1.09–6.19) 2.91 (1.19–5.84) 2.26 (0.98–4.63) 2.47 (1.13–5.53)
[195] [195] [176] [178]
DAS28-4(ESR) remission/LDA 2.48 (1.05–4.95) 2.46 (1.07–4.76) 1.70 (0.89–4.14) 1.95 (0.81–3.82)
[126] [127] [115] [117]
DAS28-4(ESR) moderate/high disease activity 3.56 (1.17–7.13) 3.58 (1.36–8.33) 2.60 (0.87–5.16) 2.68 (1.34–8.23)
[107] [107] [115] [115]

a Mean CRP was calculated as the average CRP value during each time period (>BL–W24 or >W24–48)

CRP, C-reactive protein; DAS28-4(ESR), Disease Activity Score in 28 joints, erythrocyte sedimentation rate; HAQ-DI, Health Assessment Questionnaire-Disability Index; IQR, interquartile range; LDA, low disease activity; MTX, methotrexate; n, number of pts meeting assessment criteria; QD, once daily


Conclusion: Although clinical/functional responses were generally similar between treatment groups, numerical improvements were seen for some efficacy endpoints with tofacitinib + MTX vs tofacitinib + PBO. A numerically higher CRFP rate may be associated with higher DAS28-4(ESR) disease activity. CRP changes up to W48 may not trend with CRFP status.


REFERENCES:

[1]Cohen et al. Lancet Rheumatol 2019; 1: E23-34.


Acknowledgements: Study sponsored by Pfizer Inc. Medical writing support was provided by Anthony G McCluskey, CMC Connect, and funded by Pfizer Inc.


Disclosure of Interests: Stanley B. Cohen Consultant of: AbbVie, Eli Lilly, Genentech, Gilead Sciences, Pfizer Inc, Grant/research support from: AbbVie, Eli Lilly, Genentech, Gilead Sciences, Pfizer Inc, Yi-Hsing Chen Grant/research support from: Bristol-Myers Squibb, GlaxoSmithKline, Pfizer Inc, Naonobu Sugiyama Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Jose Luis Rivas Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Annette Diehl Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Tatjana Lukic Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Jerome Paulissen Consultant of: Pfizer Inc, Haiyun Fan Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Tomohiro Hirose Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Edward Keystone Speakers bureau: AbbVie, Amgen, F. Hoffman-La Roche, Janssen, Merck, Novartis, Pfizer Inc, Sanofi Genzyme, Consultant of: AbbVie, Amgen, Bristol-Myers Squibb, Celltrion, Eli Lilly, F. Hoffman-La Roche, Gilead Sciences, Janssen, Merck, Myriad Autoimmune, Pfizer Inc, Sandoz, Sanofi Genzyme, Samsung Bioepsis, Grant/research support from: Amgen, Merck, Pfizer Inc, PuraPharm

Citation: Ann Rheum Dis, volume 80, supplement 1, year 2021, page 564
Session: Rheumatoid arthritis - non biologic treatment and small molecules (POSTERS only)