Background/Purpose: Depression and anxiety are common in patients (pts) with RA¹ and can lead to reduced quality of life, functional capacity, and RA treatment response.^2-4 Elevated IL-6 levels have been associated with depressive symptoms in pts with RA.⁵ The 36-Item Short Form Health Survey (SF-36) Mental Component Summary score (MCS) ≤ 38 has been used as an identifier of probable major depressive disorder (pMDD) and/or probable generalized anxiety disorder (pGAD) in pts with RA.⁶ Tofacitinib is an oral JAK inhibitor for the treatment of RA. We assessed the prevalence of pMDD and/or pGAD by SF-36 MCS ≤ 38 status in tofacitinib clinical trials for RA, and tofacitinib efficacy by baseline (BL) pMDD and/or pGAD status.

Methods: In this post hoc analysis, data were pooled from 5 Phase (P)3 trials and 1 P3b/4 trial. Pts receiving tofacitinib 5 or 10 mg BID, adalimumab 40 mg every other week (ADA), or placebo (PBO), with a non-missing BL SF-36 MCS, were included. Demographics and BL disease characteristics were reported by BL pMDD and/or pGAD status (SF-36 MCS ≤ 38 [presence] or > 38 [absence]). At Months (M)3/6/9/12: SF-36 MCS change from BL (∆) was estimated by modeling of pooled data, and the % of pts with pMDD and/or pGAD was reported. Efficacy endpoints were estimated at M3/6/12 by linear models, comparing tofacitinib-treated pts by BL pMDD and/or pGAD status.

Results: BL pMDD and/or pGAD were reported in 44.5%, 39.8%, 45.4%, and 39.1% of pts receiving tofacitinib 5 mg BID, tofacitinib 10 mg BID, ADA, and PBO, respectively. At BL, higher CRP levels and worse disability, fatigue, pain, and sleep were reported in pts with pMDD and/or pGAD vs those without (Table 1). A numerically, and sometimes significantly (p < 0.05), greater increase in SF-36 MCS was reported in pts receiving tofacitinib vs PBO or ADA (Figure 1a). The % of pts with BL pMDD and/or pGAD who continued to have pMDD and/or pGAD reduced over time, and was generally lower in pts receiving tofacitinib vs PBO or ADA (Figure 1b). In tofacitinib-treated pts, efficacy was generally similar regardless of BL pMDD and/or pGAD status (Table 2).

Conclusion: In this post hoc analysis, around 40% of pts with RA had BL pMDD and/or pGAD identified by SF-36 MCS ≤ 38. Improvement in SF-36 MCS was greater in pts receiving tofacitinib vs ADA or PBO. In tofacitinib-treated pts, the % with SF-36 MCS ≤ 38 (ie identified as having pMDD and/or pGAD) reduced by around 60% at M12. Tofacitinib efficacy was similar in those with and without BL pMDD and/or pGAD (identified using SF-36 MCS). Limitations include using SF-36 MCS to identify probable rather than confirmed MDD or GAD. Future research is required to replicate the findings of this study using a gold-standard psychiatric interview against which to validate the use of SF-36 MCS ≤ 38.

1. Covic T et al. BMC Psychiatry 2012; 12: 6.
2. Hattori Y et al. J Clin Rheumatol 2018; 24: 308-312.
3. Ayelen Isnardi C et al. Arthritis Rheumatol 2018; 70 (Suppl 10) Abstract 1510.
4. Matcham F et al. Rheumatology (Oxford) 2016; 55: 268-278.
5. Li YC et al. Int J Rheum Dis 2019; [Epub ahead of print].
6. Matcham F et al. BMC Musculoskelet Disord 2016; 17: 224.

Acknowledgments: Study sponsored by Pfizer Inc. Medical writing support was provided by Sarah Piggott of CMC Connect and funded by Pfizer Inc.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/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/