Secukinumab demonstrates sustained efficacy in clearing skin and improving patient-reported outcomes in patients with moderate-to-severe psoriasis through 2 years of treatment: Results from the CLEAR study
Authors: Diamant Thaçi, Lluís Puig, Kristian Reich, Tsen-Fang Tsai, Stephen Tyring, Külli Kingo, Michael Ziv, Andreas Pinter, Ronald Vender, Aude Lacombe, Summer Xia, Vaishali Bhosekar, Isabelle Gilloteau, Adriana Guana, Andrew Blauvelt
Journal: Journal of the American Academy of Dermatology (2019)

To the Editor: Secukinumab is a fully human monoclonal antibody that selectively neutralizes interleukin 17A, a key cytokine involved in the development of psoriasis.1Armstrong A.W. Vender R. Kircik L. Secukinumab in the treatment of palmoplantar, nail, scalp, and pustular psoriasis.J Clin Aesthet Dermatol. 2016; 9: S12-S16Google Scholar Secukinumab has shown long-lasting efficacy and safety in the complete spectrum of psoriatic disease, including disease localized to nails, scalp, palms and soles, and joints (peripheral and axial arthritis).1Armstrong A.W. Vender R. Kircik L. Secukinumab in the treatment of palmoplantar, nail, scalp, and pustular psoriasis.J Clin Aesthet Dermatol. 2016; 9: S12-S16Google Scholar, 2Mease P.J. McInnes I.B. Kirkham B. et al.Secukinumab inhibition of interleukin-17A in patients with psoriatic arthritis.N Engl J Med. 2015; 373: 1329-1339Crossref PubMed Scopus (555) Google Scholar, 3Baeten D. Sieper J. Braun J. et al.Secukinumab, an interleukin-17A inhibitor, in ankylosing spondylitis.N Engl J Med. 2015; 373: 2534-2548Crossref PubMed Scopus (649) Google Scholar Given the chronic and relapsing nature of psoriasis, long-term data might help to fully characterize the efficacy and safety profile of secukinumab as well as its impact on quality of life. The CLEAR study (NCT02074982) was a phase 3b, head-to-head, randomized, double-blind study on the efficacy and safety of secukinumab compared with ustekinumab over 52 weeks of treatment in adult patients with moderate-to-severe psoriasis. Results from the 16-week and 52-week time points showed higher and sustained superior efficacy of secukinumab versus ustekinumab; secukinumab use also provided a greater improvement in patient-reported outcomes (PROs), and its safety profile was comparable with ustekinumab.4Thaci D. Blauvelt A. Reich K. et al.Secukinumab is superior to ustekinumab in clearing skin of subjects with moderate to severe plaque psoriasis: CLEAR, a randomized controlled trial.J Am Acad Dermatol. 2015; 73: 400-409Abstract Full Text Full Text PDF PubMed Scopus (426) Google Scholar, 5Blauvelt A. Reich K. Tsai T.F. et al.Secukinumab is superior to ustekinumab in clearing skin of subjects with moderate-to-severe plaque psoriasis up to 1 year: results from the CLEAR study.J Am Acad Dermatol. 2017; 76: 60-69.e9Abstract Full Text Full Text PDF PubMed Scopus (231) Google Scholar Patients from the secukinumab arm who completed 52 weeks of treatment and consented to continue in the open-label extension phase received secukinumab 300 mg at week 52, followed by dosing every 4 weeks to week 100. Methods for the CLEAR study have been described in detail elsewhere.4Thaci D. Blauvelt A. Reich K. et al.Secukinumab is superior to ustekinumab in clearing skin of subjects with moderate to severe plaque psoriasis: CLEAR, a randomized controlled trial.J Am Acad Dermatol. 2015; 73: 400-409Abstract Full Text Full Text PDF PubMed Scopus (426) Google Scholar, 5Blauvelt A. Reich K. Tsai T.F. et al.Secukinumab is superior to ustekinumab in clearing skin of subjects with moderate-to-severe plaque psoriasis up to 1 year: results from the CLEAR study.J Am Acad Dermatol. 2017; 76: 60-69.e9Abstract Full Text Full Text PDF PubMed Scopus (231) Google Scholar Here, we present the efficacy, safety, and PROs from a total of 2 years of secukinumab treatment. Of 337 patients randomized to receive secukinumab 300 mg, 312 completed the 52-week study, and 303 patients entered the extension phase. In total, 277 patients completed the 2-year extension study. Irrespective of the analysis (observed, multiple imputation, modified nonresponder imputation), Psoriasis Area and Severity Index 75, 90, and 100, and Investigator's Global Assessment 2011 modified version 0/1 response rates with secukinumab treatment at week 16 were sustained up to year 2 (Table I). A similar trend was seen for the Dermatology Life Quality Index 0/1 response. Further, the mean scores for patient assessment of psoriasis-related pain, itching, and scaling severity remained low up to year 2 of secukinumab treatment (Table I). Secukinumab treatment resulted in a mean percentage of change of −85.6% for pain, −77.6% for itching, and −81.9% for scaling from baseline to year 2. Furthermore, a high proportion of patients achieved complete relief (score 0) of psoriasis-related pain, itching, and scaling at week 16, and the response was sustained up to year 2 (Table I).Table IEfficacy and patient-reported outcomes through year 2 of secukinumab 300-mg treatmentEfficacyWeek 16Year 1Year 2As observedMImNRIAs observedMImNRIAs observedMImNRIPASI 7594.5 (310/328)94.2 (315/334)93.1 (311/334)93.7 (282/301)92.4 (308/334)91.6 (306/334)89.6 (138/154)83.1 (278/334)83.8 (280/334)PASI 9080.5 (264/328)80.1 (268/334)79.0 (264/334)78.4 (236/301)76.3 (255/334)74.9 (250/334)74.7 (115/154)62.6 (209/334)66.8 (223/334)PASI 10045.1 (148/328)45.0 (150/334)44.3 (148/334)48.2 (145/301)45.8 (153/334)44.9 (150/334)47.4 (73/154)36.9 (123/334)38.6 (129/334)IGA mod 2011 0/184.5 (277/328)84.3 (282/334)83.2 (278/334)81.7 (246/301)80.2 (268/334)78.1 (261/334)68.8 (106/154)66.5 (222/334)66.5 (222/334)PROsWeek 16Year 1Year 2As observedLOCFAs observedLOCFAs observedLOCFDLQI 0/172.2 (236/327)71.9 (238/331)71.9 (210/292)71.6 (237/331)66.0 (105/159)65.9 (218/331)Pain, mean score (m)0.8 (327)0.8 (333)0.8 (292)0.8 (333)0.7 (159)0.9 (333)Itching, mean score (m)1.2 (327)1.2 (333)1.2 (292)1.3 (333)1.3 (159)1.5 (333)Scaling, mean score (m)0.8 (327)0.8 (333)1.0 (292)1.0 (333)1.1 (159)1.3 (333)Complete relief∗Complete relief of psoriasis-related pain, itching, and scaling was defined as absence of symptoms (item score of 0) in patients with baseline score for symptom >0.As observedWeek 16Year 1Year 2Pain69.4 (177/255)67.1 (151/225)70.9 (90/127)Itching49.7 (157/316)48.9 (138/282)47.4 (72/152)Scaling61.2 (197/322)53.3 (153/287)54.8 (86/157)Values are % (n/m), except where indicated. Efficacy variables and PROs were primarily assessed by using observed values (no imputation of missing values). In addition, the MI and mNRI methods were used as sensitivity analyses for efficacy variables, and the LOCF method was used for PROs. Missing values were imputed in MI analysis by using the missing at random assumption. In mNRI analyses, the missing values were imputed as nonresponse regardless of the reason for missing data, except if the patient had been a responder for 2 consecutive visits before the study completion or discontinuation or if the patient had been a responder at visits both before and after the missed visit. In LOCF analyses, the last available measurement for each patient was carried forward to all later visits. DLQI, Dermatology Life Quality Index; IGA mod 2011, Investigator Global Assessment 2011 modified version; LOCF, last observation carried forward; m, number of patients evaluable; MI, multiple imputation; mNRI, modified nonresponder imputation; n, number of patients with response; PASI, Psoriasis Area Severity Index; PROs, patient-reported outcomes.∗ Complete relief of psoriasis-related pain, itching, and scaling was defined as absence of symptoms (item score of 0) in patients with baseline score for symptom >0. Open table in a new tab Values are % (n/m), except where indicated. Efficacy variables and PROs were primarily assessed by using observed values (no imputation of missing values). In addition, the MI and mNRI methods were used as sensitivity analyses for efficacy variables, and the LOCF method was used for PROs. Missing values were imputed in MI analysis by using the missing at random assumption. In mNRI analyses, the missing values were imputed as nonresponse regardless of the reason for missing data, except if the patient had been a responder for 2 consecutive visits before the study completion or discontinuation or if the patient had been a responder at visits both before and after the missed visit. In LOCF analyses, the last available measurement for each patient was carried forward to all later visits. DLQI, Dermatology Life Quality Index; IGA mod 2011, Investigator Global Assessment 2011 modified version; LOCF, last observation carried forward; m, number of patients evaluable; MI, multiple imputation; mNRI, modified nonresponder imputation; n, number of patients with response; PASI, Psoriasis Area Severity Index; PROs, patient-reported outcomes. Among adverse events of interest, Candida infections were reported in 24 (7.2%) patients (all events were nonserious and did not lead to study discontinuation) and malignant or unspecified tumors were reported in 5 (1.5%) patients. Neutropenia was reported in 1 patient during the first year of treatment (mild severity, not associated with any infection or opportunistic infections). Overall, there was no increase in the rate of adverse events, and no new or unexpected signals were identified (Table II).Table IIAdverse events during 2-year study periodAdverse eventSecukinumab 300 mgOverall, N = 335, n (%)Up to year 1, N = 335, n (%)From >1 year to end of study, N = 307, n (%)Any adverse event299 (89.3)286 (85.4)198 (64.5)Serious adverse event41 (12.2)32 (9.6)13 (4.2)Death0 (0)0 (0)0 (0)Adverse events leading to study treatment discontinuation18 (5.4)11 (3.3)8 (2.6)Primary system organ class Infections and infestations231 (69.0)197 (58.8)137 (44.6)Most common (≥5%)∗Preferred term. Nasopharyngitis96 (28.7)77 (23.0)39 (12.7) Headache50 (14.9)40 (11.9)18 (5.9) Upper respiratory tract infection42 (12.5)31 (9.3)23 (7.5) Arthralgia36 (10.7)26 (7.8)13 (4.2) Influenza33 (9.9)22 (6.6)12 (3.9) Oropharyngeal pain32 (9.6)28 (8.4)4 (1.3) Back pain29 (8.7)21 (6.3)11 (3.6) Pruritus25 (7.5)20 (6.0)6 (2.0) Diarrhea23 (6.9)23 (6.9)4 (1.3) Psoriasis22 (6.6)12 (3.6)11 (3.6) Cough21 (6.3)13 (3.9)10 (3.3) Bronchitis20 (6.0)13 (3.9)9 (2.9) Fatigue20 (6.0)18 (5.4)2 (0.7) Eczema19 (5.7)15 (4.5)5 (1.6) Conjunctivitis18 (5.4)16 (4.8)4 (1.3)Select adverse events of interest Candida infections†High-level term.24 (7.2)19 (5.7)8 (2.6)Oral candidiasis15 (4.5)12 (3.6)5 (1.6)Vulvovaginal candidiasis4 (1.2)3 (0.9)1 (0.3)Genital candidiasis2 (0.6)1 (0.3)1 (0.3)Esophageal candidiasis2 (0.6)2 (0.6)0 (0)Balanitis candida1 (0.3)0 (0)1 (0.3)Candida infection1 (0.3)1 (0.3)0 (0)Oropharyngeal candidiasis1 (0.3)1 (0.3)0 (0)Skin candida1 (0.3)1 (0.3)0 (0) Malignant or unspecified tumors‡Standard MedDRA query.5 (1.5)4 (1.2)1 (0.3)Malignant melanoma in situ2 (0.6)2 (0.6)0 (0)Basal cell carcinoma1 (0.3)0 (0)1 (0.3)Keratoacanthoma1 (0.3)1 (0.3)0 (0)Lung adenocarcinoma1 (0.3)1 (0.3)0 (0)Events listed under Candida infections and Malignant or unspecified tumors are preferred terms. One year is defined as 365 days.∗ Preferred term.† High-level term.‡ Standard MedDRA query. Open table in a new tab Events listed under Candida infections and Malignant or unspecified tumors are preferred terms. One year is defined as 365 days. In conclusion, the 2-year results from the CLEAR study confirm the sustained efficacy and improved PROs provided by secukinumab in patients with moderate-to-severe plaque psoriasis, while maintaining a favorable safety profile. The authors thank Dhaval Gupta, MPH (Novartis Healthcare Pvt Ltd, India), and Jackie L. Johnson, PhD (Novartis Ireland Ltd), for providing medical writing support, which was funded by Novartis Pharma AG, Basel, Switzerland, in accordance with Good Publication Practice guidelines (http://www.ismpp.org/gpp3).