THU0196 TOFACITINIB IN PATIENTS WITH RHEUMATOID ARTHRITIS AND INDICATIVE OF DEPRESSION AND/OR ANXIETY: A POST HOC ANALYSIS OF PHASE 3 AND PHASE 3B/4 CLINICAL TRIALS
Authors: G. Citera, R. Jain, F. Irazoque-Palazuelos, R. Guzman, H. Madariaga, D. C. Gruben, L. Wang, L. Stockert, M. A. Hsu, K. Santana, A. Ebrahim, D. Ponce de Leon
Journal: Annals of the Rheumatic Diseases (2020)

Background: Depression/anxiety are common in RA pts. SF-36 MCS ≤38 can identify probable major depressive disorder and/or probable generalised anxiety disorder (pMDD/pGAD) in RA pts. Tofacitinib is an oral JAK inhibitor for the treatment of RA. Objectives: To assess pMDD/pGAD prevalence in the tofacitinib RA program and efficacy by baseline (BL) pMDD/pGAD status. Methods: Data from pts receiving tofacitinib, ADA, or PBO were pooled from 5 Phase (P)3 and 1 P3b/4 trials. Demographics/BL characteristics were reported by BL pMDD/pGAD (SF-36 MCS ≤38, presence; &gt;38, absence). Month (M)3/6/9/12 SF-36 MCS change from BL (Δ) was estimated, and % with pMDD/pGAD reported. M3/6/12 efficacy outcomes compared tofacitinib-treated pts by BL pMDD/pGAD. Results: BL pMDD/pGAD was seen in 44.5% (tofacitinib 5 mg BID), 39.8% (tofacitinib 10 mg BID), 45.4% (ADA 40 mg Q2W) and 39.1% (PBO) of pts. pMDD/pGAD pts had higher BL CRP and worse disability, fatigue, pain and sleep vs pts without. SF-36 MCS increases were greater for tofacitinib vs PBO/ADA (Fig 1a). The % of pts with BL pMDD/pGAD who continued to have pMDD/pGAD reduced over time, and was generally lower for tofacitinib vs PBO/ADA (Fig 1b). Regardless of BL pMDD/pGAD, efficacy was generally similar for tofacitinib 5 mg BID (Table) and 10 mg BID. Conclusion: ~40% of RA pts had BL pMDD/pGAD. SF-36 MCS improvements were greater for tofacitinib vs PBO/ADA. With tofacitinib, % of pts with SF-36 MCS ≤38 reduced by ~60% at M12. Tofacitinib efficacy was similar in pts with/without BL pMDD/pGAD. Limitations include using SF-36 MCS to identify probable rather than confirmed MDD or GAD. Future research using gold standard psychiatric interviews to validate use of SF-36 MCS ≤38 is needed. Table. M3/6/12 efficacy with tofacitinib 5 mg BID, by BL pMDD/pGAD a SF-36 MCS ≤38 SF-36 MCS &gt;38 OR (95% CI ) P value ACR20 (% ) b,c M3 55.1 57.9 0.89 (0.74, 1.08) 0.2330 M6 61.7 62.8 0.96 (0.79, 1.16) 0.6511 M12 58.4 58.6 0.99 (0.80, 1.22) 0.9279 ACR50 (% ) b,c M3 25.9 29.2 0.85 (0.70, 1.03) 0.1022 M6 36.0 38.0 0.92 (0.76, 1.11) 0.3724 M12 33.8 34.3 0.98 (0.80, 1.20) 0.8366 ACR70 (% ) b,c M3 10.1 11.0 0.91 (0.69, 1.18) 0.4704 M6 16.5 16.5 1.00 (0.79, 1.26) 0.9901 M12 18.3 17.5 1.06 (0.83, 1.34) 0.6560 DAS28-4(ESR)&lt;2.6 (% ) b,c M3 5.4 7.4 0.72 (0.49, 1.05) 0.0872 M6 5.9 8.5 0.68 (0.49, 0.94) 0.0199* M12 8.0 11.9 0.64 (0.47, 0.89) 0.0073** ΔHAQ-DI, LS mean c,d SF-36 MCS ≤38 SF-36 MCS &gt;38 Difference (95% CI ) P value M3 -0.41 -0.43 0.01 (-0.04, 0.06) 0.6008 M6 -0.49 -0.48 -0.01 (-0.06, 0.04) 0.6617 M12 -0.52 -0.52 -0.01 (-0.06, 0.05) 0.8475 *p&lt;0.05; **p&lt;0.01 Data pooled from 5 P3 and 1 P3b/4 tofacitinib trials a BL pMDD/pGAD = SF-36 MCS ≤38; b Logistic regression fit; c For PBO pts advancing to tofacitinib post-M3, only PBO data were included; d Mixed-effects linear model fit Δ, change from baseline; ACR, American College of Rheumatology; BID, twice daily; BL, baseline; CI, confidence interval; DAS28-4(ESR), Disease Activity Score in 28 joints, erythrocyte sedimentation rate; HAQ-DI, Health Assessment Questionnaire-Disability Index; LS, least squares; M, month; MCS, Mental Component Summary score; OR, odds ratio; P, Phase; pGAD, probable generalised anxiety disorder; PBO, placebo; pMDD, probable major depressive disorder; pt, patient; RA, rheumatoid arthritis; SF-36, Short Form-36 health survey Acknowledgments: Study sponsored by Pfizer Inc. Medical writing support was provided by Sarah Piggott of CMC Connect and funded by Pfizer Inc. Disclosure of Interests: Gustavo Citera Grant/research support from: AbbVie, Amgen, Eli Lilly, Gema, Genzyme, Novartis and Pfizer Inc, Consultant of: AbbVie, Amgen, Eli Lilly, Gema, Genzyme, Novartis and Pfizer Inc, Rakesh Jain Grant/research support from: Allergan, Eli Lilly, Lundbeck, Otsuka, Pfizer Inc, Shire and Takeda, Consultant of: Acadia, Alfasigma, Allergan, Eisai, Eli Lilly, Evidera, Impel, Janssen, Lundbeck, Merck, Neos Therapeutics, Neurocrine Biosciences, Osmotica, Otsuka, Pamlab, Pfizer Inc, Shire, Sunovion, Supernus, Takeda and Teva, Speakers bureau: Alkermes, Allergan, Eli Lilly, Janssen, Lundbeck, Merck, Neos Therapeutics, Neurocrine, Otsuka, Pamlab, Pfizer Inc, Shire, Sunovion, Takeda, Teva and Tris Pharmaceuticals, Fedra Irazoque-Palazuelos Consultant of: Bristol-Myers Squibb, Janssen, Pfizer Inc, Roche and UCB, Renato Guzman: None declared, Hugo Madariaga: None declared, David C Gruben Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Lisy Wang Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Lori Stockert Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Ming-Ann Hsu Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Karina Santana Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Abbas Ebrahim Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Dario Ponce de Leon Shareholder of: Pfizer Inc, Employee of: Pfizer Inc