Tofacitinib efficacy, patient‐reported outcomes and safety in patients with psoriasis and a medical history of psoriatic arthritis: Pooled analysis of two Phase <scp>III</scp> studies

Approximately 30% of patients with psoriasis have psoriatic arthritis (PsA).1 Patients with PsA with joint/skin symptoms have worse disease activity/patient-reported outcomes (PROs) than patients with only joint symptoms.2 Tofacitinib is an oral Janus kinase inhibitor for treatment of PsA. Using pooled data from two global/52-week/Phase III studies, OPT Pivotal 1 and 2 [NCT01276639/NCT01309737],3 this post hoc analysis examined the efficacy/PROs/safety of tofacitinib in patients with moderate to severe plaque psoriasis and history of PsA, and explored the role of itch/joint pain/morning stiffness in reducing depressive symptoms. In OPT Pivotal 1 and 2, patients were randomized to tofacitinib 5 or 10 mg twice daily (BID) or placebo. At Week 16, placebo-treated patients were re-randomized to tofacitinib 5 or 10 mg BID to Week 52. Efficacy outcomes, to Week 52, included proportions of patients achieving Psoriasis Area and Severity Index (PASI)75, PASI90, and those with Itch Severity Item (ISI) score improvement from baseline >2 and Hospital Anxiety and Depression Scale Depression (HADS-D) subscale score <8. Change from baseline in ISI score, joint pain assessment (JPA) score and morning stiffness on JPA score were also measured to Week 52. Mediation modelling examined tofacitinib's effect on depressive symptoms with ISI/JPA/morning stiffness as mediators. Safety outcomes included frequency of adverse events (AEs) and serious AEs (SAEs), frequency and incidence rates of AEs of special interest (AESI), discontinuation due to AEs and deaths. Of 1859 patients with psoriasis, 430 (23.1%) had PsA history. At Week 16, PASI75/PASI90 response rates, ISI score improvement from baseline >2, and change from baseline in ISI/JPA/morning stiffness were greater with tofacitinib 5 and 10 mg BID versus placebo (Figure 1a–f). Altogether, 45.2% and 46.5% of patients receiving tofacitinib 5 and 10 mg BID, respectively, had a HADS-D subscale score <8 at Week 16 (Figure 1g). Efficacy outcomes were generally maintained to Week 52. Mediation modelling analysis showed that tofacitinib's indirect effect on HADS-D via itch/joint pain represented 61.9%/38.1% of the overall effect, respectively. The frequency of AEs at Week 16 was similar across groups; the most common were upper respiratory tract infections (Table 1). SAE incidence and discontinuation due to AEs were also similar across groups at Week 16. Of the AESI reported (Table 1), with tofacitinib there were 10 adjudicated cases of herpes zoster, one patient had a serious infection, one had an adjudicated opportunistic infection, two reported an arterial thromboembolism event, four reported malignancies (excluding non-melanoma skin cancer [NMSC]) events and five reported NMSC events. In total, two patients receiving tofacitinib 5 mg BID died from MACE—one due to myocardial infarction and one due to sudden cardiac death. No venous thromboembolism was reported. PASI75/PASI90 improvements with tofacitinib 5 and 10 mg BID versus placebo were consistent with findings from patients with psoriasis treated with tofacitinib overall.4-6 Additionally, the PASI75/PASI90 and itch results were generally consistent with findings of previous studies in patients with active PsA.7-9 The safety profile was consistent with reports from the tofacitinib PsA clinical development programme.10 Limitations of this post hoc analysis include that PsA history was defined/captured based on baseline patient reports without a formal rheumatologist's assessment. In patients with psoriasis and history of PsA, tofacitinib 5 and 10 mg BID demonstrated greater improvements in skin disease/itch/joint pain/morning stiffness/depressive symptoms versus placebo at Week 16; improvements generally continued to Week 52. Mediation modelling results suggested that treatment effects on depressive symptoms were mainly mediated via itch improvements. Safety of tofacitinib in this population appeared consistent with the established profile. As patients with PsA experiencing joint/skin symptoms use more healthcare resources than patients with joint symptoms alone,2 these data can further inform clinical practice/scientific community. Medical writing support, under the direction of the authors, was provided by Julia Bárdos, PhD, and Caitlin Duncan, PhD, CMC Connect, a division of IPG Health Medical Communications, and Karleen Nicholson, PhD, on behalf of CMC Connect, and was funded by Pfizer, New York, NY, USA, in accordance with Good Publication Practice (GPP 2022) guidelines (DeTora et al.11). This study was sponsored by Pfizer. H. Bachelez has received grant support and/or has participated in advisory boards for, or acted as a speaker, consultant or investigator for, AbbVie, AnaptysBio, Biocad, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Janssen, Leo Pharma, Novartis, Pfizer Inc and UCB. C.E.M. Griffiths has received grant/research support and/or has acted as a consultant and speaker for AbbVie, Almirall, Boehringer Ingelheim, Bristol Myers Squibb, Dermavant, Eli Lilly, Evelo Biosciences, GSK, Inmagene, Janssen, Novartis, ONO Pharmaceutical, Pfizer Inc, Sun Pharma and UCB, and he is funded in part by the National Institute for Health and Care Research Manchester Biomedical Research Centre. K.A. Papp has received grant support or honoraria and/or has participated in advisory boards, steering committees for, or acted as a speaker, consultant or scientific officer for, AbbVie, Acelyrin, Akros, Amgen, Anacor, Arcutis, Astellas, Avillion, Bausch Health/Valeant, Boehringer Ingelheim, Bristol Myers Squibb, Can-Fite BioPharma, Celltrion, Coherus, Dermavant, Dermira, Dice Pharmaceuticals, Dow Pharma, Eli Lilly, Evelo, Forbion, Galapagos, Galderma, Genentech, Gilead, GSK, Incyte, Janssen, Kyowa Hakko Kirin, Leo Pharma, MedImmune, Meiji Seika Pharma, Merck, Merck Serono, Mitsubishi Pharma, Moberg Pharma, Novartis, Pfizer Inc, PRCL Research, Regeneron, Reistone, Roche, Sanofi Aventis/Genzyme, Sandoz, Sun Pharma, Takeda, UCB, vTv Therapeutics and Xencor. S. Hall has acted as a consultant for Pfizer Inc. J.F. Merola has acted as a consultant and/or investigator for AbbVie, Amgen, Biogen, Bristol Myers Squibb, Dermavant, Eli Lilly, Janssen, Leo Pharma, Novartis, Pfizer Inc, Regeneron, Sanofi, Sun Pharma and UCB. S.R. Feldman has received research support from, and has acted as a speaker and/or consultant for, AbbVie, Accordant, Advance Medical, Almirall, Alvotech, Amgen, Arcutis, Arena, Argenx, Biocon, Boehringer Ingelheim, Bristol Myers Squibb, Caremark, Celgene, Dermavant, Eli Lilly, Forté Pharma, Galderma, GSK/Stiefel, Helsinn, Informa, Janssen, Leo Pharma, Menlo, Merck & Co, Mylan, Novan, Novartis, Pfizer Inc, Qurient, Regeneron, Samsung, Sanofi, Sun Pharma, Suncare Research, the National Biological Corporation, the National Psoriasis Foundation, UCB, UpToDate, Valeant and vTv Therapeutics. He is the founder and part owner of Causa Research and is a shareholder of Sensal Health. M. Khraishi has participated in an advisory board for Pfizer Inc. H. Tan, L. Fallon, J.C. Cappelleri, A.G. Bushmakin and P. Young are employees and shareholders of Pfizer Inc. Both studies were conducted in accordance with the Declaration of Helsinki and Good Clinical Practice Guidelines of the International Council for Harmonisation, and were approved by the relevant institutional review board and/or independent ethics committee of the investigational centres. All patients provided written informed consent.