Acta Demato-Venereologica 98-3CompleteContent | Page 14

340 CLINICAL REPORT Validation of the Itch Severity Item as a Measurement Tool for Pruritus in Patients with Psoriasis: Results from a Phase 3 Tofacitinib Program Sonja STÄNDER 1 , Thomas A. LUGER 1 , Joseph C. CAPPELLERI 2 , Andrew G. BUSHMAKIN 2 , Carla MAMOLO 2 , Michael A. ZIELINSKI 3 , Anna M. TALLMAN 4 and Gil YOSIPOVITCH 5 1 Department of Dermatology and Center for Chronic Pruritus, University of Münster, Münster, Germany, 2 Pfizer Inc, Groton, CT, 3 Pfizer Inc, Collegeville, PA, 4 Pfizer Inc, New York, NY, and 5 Department of Dermatology and Itch Center, University of Miami, Miami, FL, USA Tofacitinib is an oral Janus kinase inhibitor. This post-hoc analysis aimed to investigate the psychome- tric properties of the Itch Severity Item (ISI), a nume- ric rating scale from 0 (no itching) to 10 (worst possible itching) for pruritus in psoriasis, and review the effect of tofacitinib on pruritus in patients with psoriasis parti- cipating in Phase 3 studies (N  = 3,641). The ISI showed high test–retest reliability (intra-class correlation co- efficient: 0.84). The clinically important difference was defined as a 1.48-point change, using Patient Global Assessment as an anchor. Mean changes from base- line in ISI scores with tofacitinib were significant- ly greater than placebo by Day 2 and exceeded the clinically important difference by Week 4 and Week 2 for tofacitinib 5 and 10 mg twice daily, respectively. The sound psychometric properties of the ISI as an as- sessment tool for pruritus in psoriasis were confirmed. Tofacitinib provided clinically meaningful improve- ments in psoriatic pruritus versus placebo. Key words: pruritus; psoriasis; tofacitinib; Itch Severity Item; clinically important difference; Patient Global Assessment. Accepted Nov 24, 2017; Epub ahead of print Nov 28, 2017 Acta Derm Venereol 2018; 98: 340–345. Corr: Michael A. Zielinski. Pfizer Inc, 500 Arcola Road, Collegeville, PA 19426, USA. E-mail: [email protected] P ruritus is a common symptom of psoriasis, affecting 64–97% of patients with psoriasis (1–5) and resulting in reduced health-related quality of life (HRQoL) (6). Pruritus has been rated as the most bothersome symptom for patients (7), and is more likely to result in reduced productivity or absence from work than other symptoms such as pain (8). Despite the high prevalence and impact of pruritus, anti-pruritic therapies are generally ineffective (9, 10), and there is a paucity of clinically relevant data in rela- tion to plaque psoriasis and the efficacy of treatments to relieve itch. Tofacitinib is an oral Janus kinase inhibitor. The efficacy and safety of tofacitinib 5 and 10 mg twice daily (BID) in patients with moderate to severe chronic plaque psoriasis has been demonstrated in Phase 2 (11) and Phase 3 (12–15) trials of up to 56 weeks’ duration, and in a long-term extension study with efficacy endpoints reported through doi: 10.2340/00015555-2856 Acta Derm Venereol 2018; 98: 340–345 24 months and safety reported over 33 months of expo- sure (13). Co-primary efficacy endpoints of the Phase 2 and Phase 3 studies included the proportions of patients achieving a Physician’s Global Assessment (PGA) of ‘clear’ or ‘almost clear’, and the proportions of patients achieving a reduction ≥75% in the Psoriasis Area and Severity Index (PASI75). The efficacy and safety of tofacitinib has also been studied in several immune- mediated inflammatory diseases, including rheumatoid arthritis (16–21), psoriatic arthritis (22–24), ankylosing spondylitis (25), Crohn’s disease (26–28), and ulcerative colitis (29, 30). Moreover, the impact of tofacitinib on pruritus has previously been reported in Phase 2 studies of tofacitinib as a topical treatment for atopic dermatitis (31) and psoriasis (32), and Phase 2 and 3 studies of tofacitinib as an oral treatment for psoriasis (33–36). Because patients with psoriasis experience reduced HRQoL (6), some generic instruments that assess life quality, irrespective of the illness or condition of the patient, may be useful in evaluating their wellbeing and functioning. Examples of generic questionnaires that capture various aspects of health status include the 5-level EuroQoL 5-dimension scale (EQ-5D-5L) (37) and the Medical Outcomes Study 36-item Short Form (SF-36) (38). On the other hand, disease-specific instru- ments have the advantage of being specifically tailored to measure the special or distinctive characteristics found in particular conditions or diseases. Examples of disease-specific instruments include the Dermatology Life Quality Index (DLQI) (39) and PASI (40), which are used to assess dermatology-related HRQoL and clinical outcomes in psoriasis. However, neither provide a direct measure of pruritus. The Itch Severity Item (ISI) is an 11-point numeric rating scale (NRS) that was used to assess the severity of pruritus in the Phase 3 clinical trials of tofacitinib for the treatment of patients with moderate to severe chronic plaque psoriasis (34–36). Other Itch NRSs have been validated for use in patients with chronic pruritus (41) and patients with moderate to severe plaque psoriasis (42). An earlier version of the ISI has previously been validated as an assessment tool for pruritus in a Phase 2 study of oral tofacitinib in patients with psoriasis (43). Here, we extend these previous analyses in Phase 2 studies and evaluate the psychometric properties of the This is an open access article under the CC BY-NC license. www.medicaljournals.se/acta Journal Compilation © 2018 Acta Dermato-Venereologica.