Acta Dermato-Venereologica 99-9CompleteContent

820 SHORT COMMUNICATION Secukinumab Provides Rapid Relief From Itching and Pain in Patients with Moderate-to-Severe Psoriasis: Patient Symptom Diary Data from Two Phase 3, Randomized, Placebo-controlled Clinical Trials Gil YOSIPOVITCH 1 , Jennifer SOUNG 2 , Jonathan WEISS 3 , Elisa MUSCIANISI 4 , Xiangyi MENG 4 , Isabelle GILLOTEAU 5 , and Boni E. ELEWSKI 6 1 Dr Phillip Frost Department of Dermatology and Cutaneous Surgery, Miami Itch Center, University of Miami, Leonard M. Miller School of Medicine, Miami, FL, 2 Southern California Dermatology, Santa Ana, CA, 3 Gwinnett Clinical Research Center, Snellville, GA, 4 Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA, 5 Novartis Pharma AG, Basel, Switzerland, and 6 University of Alabama at Birmingham School of Medicine, Birmingham, AL, USA Accepted Apr 16, 2019; E-published Apr 16, 2019 In patients with psoriasis, severe itching of the skin and pain are among the most bothersome symptoms of the disease (1). Itching is one of the most prevalent symptoms, affect ing > 75% of patients with psoriasis (2, 3), whereas pain has been reported in approximately 45% of patients with psoriasis (3). For many patients, the presence of severe itch ing is associated with increased disease severity, reduced health-related quality of life and work productivity, and decreased psychosocial well-being (4, 5). Patient symptoms are often underestimated; therefore, treatments that address all aspects of the disease, including rapid and sustained improvement in itching and pain, are critical for improving the overall quality of life of patients with psoriasis. Secukinumab is a fully human monoclonal antibody that selectively neutralizes interleukin 17A, a cornerstone cytokine involved in the development of psoriasis. Se cukinumab has shown long-lasting efficacy and safety in the complete spectrum of psoriasis manifestations, including nails, scalp, palmoplantar, and psoriatic arthritis (6–12). A previous analysis of pooled Psoriasis Symptom Diary (PSD) data from the ERASURE (NCT01365455) and FIXTURE (NCT01358578) pivotal studies showed that treatment with secukinumab resulted in significant improvements in patient-reported psoriasis-related itching, pain, and sca ling symptoms at week 12 compared with placebo (13). This report highlights the effectiveness of secukinumab in achieving rapid improvements in patient-reported itching and pain within the first 4 weeks of treatment using pooled PSD data from the randomized, double-blind, placebo- controlled, phase 3 ERASURE and FIXTURE clinical trials. METHODS AND RESULTS Full details of the study designs and patient enrollment criteria for ERASURE and FIXTURE have been described previously (6). Patient-reported itching and pain were assessed during the first 12 weeks of treatment using the PSD, a validated and responsive tool designed to capture the daily signs and symptoms of psoriasis reported by the patient, based on 16 items evaluating psoriasis- related characteristics (1, 14). The results reported here focus on severity of psoriasis-related itching and pain over the past 24 h, on a scale from 0 (no itching/pain) to 10 (itching/pain as bad as you can imagine) (1). Weekly means for the PSD categories of itching and pain were derived during the induction treatment period (weeks 1–12), defined as the sum of the scored item over the course of the week divided by the number of days on which the item was complet ed. Values were designated as missing if ≥ 4 daily assessments doi: 10.2340/00015555-3195 Acta Derm Venereol 2019; 99: 820–821 were missing for the corresponding question. Missing values were imputed using the last observation carried forward method. The absolute change in itching and pain scores from baseline to weeks 2, 4, and 12 were compared across treatment groups using analysis of covariance. The proportion of patients within each treatment arm who achieved no or minimal itching/pain (score of 0 or 1) was also assessed weekly and compared across treatment groups to examine trends over time in the proportion of patients who remained with no or minimal itching/pain. The proportions of patients who achieved different thresholds of improvement (i.e., no improvement or improvement ≤ 2 points, > 2 to 3 points, > 3 to 5 points, or > 5 points) at week 12 were also assessed (14). All analyses were for hypothesis generation only. No adjustment was made for multiple comparisons. Among the 40.2% of patients (820/2,042) who completed the PSD at baseline, baseline demographics and disease characteristics were similar across all treatment groups and were consistent with analyses previously published from FIXTURE and ERASURE (Table SI 1 ) (6, 13). Patients treated with secukinumab demonstrated rapid improve ments in itching severity, with mean improvements in scores from baseline observed as early as week 2 in both secukinumab dose groups (150 mg, −1.36; 300 mg, −1.38) that were significantly greater than those with placebo (−0.25) and etanercept (−0.69). Significantly greater improvements from baseline were also ob served at week 4 in both secukinumab dose groups (150 mg, −2.87; 300 mg, −3.03) compared with placebo (−0.42) and etanercept (−1.86) (p < 0.05 for all comparisons vs placebo and etanercept) (Fig. S1a 1 ). The improvements in itching scores were maintained through week 12 in the secukinumab dose groups (150 mg, −4.90; 300 mg, −5.14) relative to placebo (−0.40) and etanercept (−3.80). Similarly, improvements in pain were reported as early as week 2 in both secukinumab dose groups (150 mg, −1.48; 300 mg, −1.55) compared with placebo (−0.07) and etanercept (−0.74), with significantly greater improvements also observed at week 4 in both secukinumab dose groups (150 mg, −2.65; 300 mg, −2.92) compared with placebo (−0.28) and etanercept (−1.81) (p < 0.05 for all comparisons vs placebo and etanercept; Fig. S1b 1 ). The improvements in pain scores with secukinumab treatment were maintained through week 12 in both dose groups (150 mg, −4.02; 300 mg, −4.52) relative to placebo (−0.16) and etanercept (−3.48). At week 2, the proportion of patients who achieved no (0) or minimal (1) itching was significantly greater with secukinumab 300 mg than with placebo (6.0% vs 1.4%; p < 0.05), and numeri cal improvements were observed with both secukinumab doses vs etanercept (Fig. S1c 1 ). At week 4, the proportions of patients who achieved no/minimal itching were significantly greater with secukinumab 150 and 300 mg than with placebo (14.5% and 19.4% vs 2.4%; p < 0.05); secukinumab 300 mg also showed significant improvements vs etanercept (19.4% vs 9.0%; p < 0.05). Similar trends were observed with improvements in patient-reported pain https://www.medicaljournals.se/acta/content/abstract/10.2340/00015555-3195 1 This is an open access article under the CC BY-NC license. www.medicaljournals.se/acta Journal Compilation © 2019 Acta Dermato-Venereologica.

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