Introduction: Netakimab (NTK), an original humanized anti-interleukin-17 monoclonal antibody, showed therapeutic efficacy in moderate-to-severe plaque psoriasis in a phase 2 clinical study. Herein we report the results of 54 weeks of a phase 3 PLANETA trial aimed to evaluate the efficacy and safety of two NTK regimens vs. placebo. Methods: Two hundred thirteen patients with moderate-to-severe plaque psoriasis were randomly assigned to receive NTK 120 mg once every 2 weeks (NTK Q2W), NTK 120 mg once every 4 weeks (NTK Q4W) or placebo. During the first 3 weeks, patients received subcutaneous injections of NTK or placebo (according to the allocation) once a week. Patients in the NTK Q2W group then received NTK at weeks 4, 6, 8 and 10. Subjects in the NTK Q4W group received NTK at weeks 6 and 10 and placebo at weeks 4 and 8. Patients in the placebo group received placebo injections at weeks 4, 6, 8 and 10. Treatment was unblinded at week 12. During the open-label phase, patients in both NTK groups continued to receive NTK Q4W. The primary efficacy endpoint was the proportion of patients in each group who achieved a C 75% reduction from baseline in psoriasis area and severity index (PASI 75) at week 12. Results: A total of 77.7%, 83.3% and 0% of patients had a PASI 75 response at week 12 in the NTK Q2W, NTK Q4W and placebo groups, respectively (P \ 0.0001, Fisher's exact test, ITT). The effect was maintained throughout the 1-year treatment. NTK showed a good safety profile and low immunogenicity. Conclusion: Treatment with NTK results in high rates of sustained clinical response in patients with moderate-to-severe plaque psoriasis. The study is ongoing; thus, long-term use efficacy and safety data are forthcoming.

No abstract

Netakimab, the original monoclonal antibody against IL-17A, is an innovative drug for the treatment of moderate-to-severe plaque psoriasis in patients who have indications for systemic therapy or phototherapy. Netakimab was approved in Russian Federation, registration certificate number ЛП-005439 from 04.04.2019. This article outlines the first 12-week results of a phase III clinical trial in patients with psoriasis.Materials and methods. The BCD-085-7 study (PLANETA) is a comparative, randomized, double-blind, placebo-controlled phase 3 clinical study of the efficacy and safety of netakimab in patients with moderate-to-severe plaque psoriasis. This review presents the results of the first 12 weeks. The study is ongoing at the moment, the total duration of treatment for each patient is 3 years (154 weeks). Patients were randomized in a ratio of 2:2:1 into one of three arms: group 1 received netakimab subcutaneously at a dose of 120 mg once a week for the first three weeks (induction) and then once every 2 weeks up to week 10, group 2 received netakimab subcutaneously at a dose of 120 mg once a week for the first three weeks (induction) and then once every 4 weeks up to week 10, group 3 received a placebo subcutaneously on day 1 at weeks 0, 1, 2, 4, 6, 8 10. In order to maintain a double-blind design, placebo was administered to patients in group 2 at weeks 4 and 8.Results. Both netakimab groups showed a significant superiority over placebo (p < 0.001) and the absence of statistically significant differences between the two regimens of therapy (p > 0.05) across all endpoints. PASI 75 at week 12 was reached by 77.65 % of patients using netakimab once every 2 weeks and 83.33 % of patients using netakimab once every 4 weeks (ITT population). The rate of clear and almost clear skin (sPGA 0–1) was reached by 81.18 and 79.76 % of patients using netakimab once every 2 weeks and once every 4 weeks, respectively. The safety assessment showed no statistically significant differences between the groups, the incidence rate of adverse events in netakimab arms was not higher than in the placebo arm. There were no cases of early withdrawal due to adverse events and cases of grade 4 toxicity according to CTCAE 4.03. During the 12 weeks of the study, one serious adverse event was registered in group 2 (pneumonia grade 3), which was recovered without any consequences. The immunogenicity assessment showed binding antibodies formation at week 12 in one patient who received BCD-085 every 2 weeks. Neutralizing antibodies were not detected. Conclusion. Netakimab showed high efficacy in the treatment of psoriasis, more than 80 % of patients achieved PASI 75 and sPGA 0–1 (clear and almost clear skin) by the week 12 of treatment. The drug showed a favorable safety profile and low immunogenicity. Based on the study results the regimen once a week during the first 3 weeks (induction), then once every 4 weeks was chosen for medical use in patients with psoriasis.

В связи с высоким риском развития у одного пациента нескольких иммунновоспалительных заболеваний (псориаз, псориатический артрит -ПсА и болезнь Крона -БК) крайне актуальными являются их ранняя диагностика и адекватная терапия. Междисциплинарной рабочей группой, в которую вошли эксперты ревматологи, гастроэнтерологи и дерматологи, разработан проект рекомендаций по ранней диагностике, методам оценки активности и показаниям к применению генно-инженерных биологических препаратов у пациентов с сочетанной иммуновоспалительной патологией -псориазом, ПсА, БК. В соответствии с решением Совета экспертов и результатами обсуждения со специалистами из разных регионов Российской Федерации будут предприняты дальнейшие шаги для валидации рекомендаций. Ключевые слова: междисциплинарные рекомендации; псориаз; псориатический артрит; болезнь Крона. Контакты: Татьяна Викторовна Коротаева; tatianakorotaeva@gmail.com; Марианна Михайловна Хобейш; mkhobeysh@yandex.ru; Елена Александровна Белоусова; eabelous@yandex.ru Для ссылки: Абдулганиева ДИ, Бакулев АЛ, Белоусова ЕА и др. Проект междисциплинарных рекомендаций по диагностике, методам оценки степени активности, терапевтической эффективности и применению генно-инженерных биологических препаратов у пациентов с сочетанными иммуновоспалительными заболеваниями (псориаз, псориатический артрит, болезнь Крона). Современная ревматология. 2018;12(3):4-18. Draft interdisciplinary guidelines for diagnosis, methods for estimation of the degree of activity, for evaluation of therapeutic efficacy, and for use of biological agents in patients with concomitant immunoinflammatory diseases (psoriasis, psoriatic arthritis, Crohn's disease)Due to that one patient may be at high risk for developing several immunoinflammatory diseases (psoriasis, psoriatic arthritis (PsA), and Crohn's disease (CD)), their early diagnosis and adequate therapy are extremely relevant. The Interdisciplinary Working Group that includes experts in rheumatology, gastroenterology and dermatology has developed draft guidelines for early diagnosis, methods for activity assessments and for indications for the use of biological agents in patients with concomitant immunoinflammatory diseases (psoriasis, PsA, and CD).Проект междисциплинарных рекомендаций по диагностике, методам оценки степени активности, терапевтической эффективности и применению генноинженерных биологических препаратов у пациентов с сочетанными иммуновоспалительными заболеваниями (псориаз, псориатический артрит, болезнь Крона) Предпосылки для создания рекомендацийПсориаз, псориатический артрит (ПсА) и воспалительные заболевания кишечника (ВЗК) относятся к многофакторным хроническим иммуновоспалительным потенциально инвалидизирующим заболеваниям, при которых выявляют сходные генетические и иммунологические факторы развития, в частности генетический полиморфизм интерлейкина (ИЛ) 23R, определяющий сигнальный ИЛ12/23-путь иммунопатогенеза [1][2][3][4][5][6].В связи с высоким риском развития у одного пациента нескольких иммуновоспалительных заболеваний, крайне актуальными явл...

Background:Psoriatic arthritis (PsA) is associated with multiple manifestations, resulting in reduced health-related quality of life (HR-QoL) of patients (pts). Netakimab (NTK) is a humanized anti-IL17A antibody approved for the treatment of moderate-to-severe plaque psoriasis.Objectives:To assess the impact of NTK on patient-reported outcomes (PROs) in active PsA pts, based on data of 24-week (wk) data from the ongoing PATERA study (NCT03598751).Methods:PATERA is an international double-blind, placebo-controlled clinical study. 194 eligible adult pts with PsA (CASPAR, 2006), with inadequate response to csDMARD or one TNFi, were randomized (1:1) to receive NTK 120 mg or placebo (PBO) at Wk 0, 1, 2, 4, 6, 8, 10, 14, 18, 22. Pts from PBO arm failed to achieve ACR20 (20% improvement of the American College of Rheumatology criteria) by Wk 16 were switched to NTK. PROs included changes from baseline (BL) in Work Productivity and Activity Impairment General Health (WPAI GH), 36-item Short Form Health Survey (SF-36), European Quality of Life Questionnaire (EQ-5D-5L), Dermatology Quality of Life Index (DLQI), Health assessment questionnaire disability index (HAQ-DI).Results:BL demographics and PsA characteristics were similar between treatment arms (Table 1). The proportion of pts with an improvement of ≥1 level in EQ-5D domains at Wk 24 (among pts who reported problems at BL) was higher in NTK arm compared to PBO (Figure 1). The assessment of physical disability showed positive dynamics in NTK arm: at Wk 24 mean change in HAQ-DI from BL was -0.6 for NTK vs -0.1 for PBO (p<0.0001). DLQI was assessed in pts with ≥3% body surface area involvement at BL (N=76 in NTK arm, N=72 in PBO arm). A greater reduction in DLQI was observed in NTK-treated pts (-11.4) compared to PBO-treated pts (-1.8) (p<0.0001). After 24 wks WPAI response for NTK was better than for PBO in all aspects, except work time missed due to PsA (Table 2). Positive dynamics were reported for both SF-36 components, however, the difference between NTK and PBO was not statistically significant. At Wk 24 mean change from baseline in SF-36 PCS in NTK arm was 10.4 vs 7.7 in PBO (p=0.29), mean change in SF-36 MCS was 6.4 vs 9.0 in the same arms, respectively (p=0.56).Table 1.BL demographics and PsA characteristicsArmNTK (N=97)PBO (N=97)Age (years)*44.0 (11.7)43.1 (11.9)Male, n (%)52 (53.6)50 (51.6)PsA duration, mo*63.1 (73.1)68.2 (77.5)HAQ-DI*1.15 (0.6)1.21 (0.6)DLQI*14.8 (6.5)13.9 (7.3)SF36 PCS*32.39 (9.5)31.10 (8.9)SF36 MCS*45.29 (10.7)46.04 (11.5)* mean (standard deviation), N=number of pts, mo=months, PsA=psoriatic arthritis, HAQ-DI=Health assessment questionnaire disability index, DLQI=Dermatology Quality of Life Index, SF36=36-item Short Form Health Survey, MCS=Mental Component Summary, PCS=Physical Component SummaryTable 2.WPAI change from BL at wk 24 (mean±standard deviation)ParameterNTKPBOAbsenteeism (%)-8.7±29.1N=60-9.1±31.8N=47Presenteeism (%)-22.1 ±22.1N=57-1.0±26.5N=42Overall work impairment (%)-18.6±21.8N=570.6±26.7N=42Activity impairment (%)-25.5±25.2N=96-5.4±29.1N=97N=number of pts in the analysis categoryFigure 1.Improvement in EQ-5D categoriesConclusion:NTK demonstrated rapid improvement in QoL, work productivity and physical function in pts with PsA.Acknowledgments:This study was sponsored by JSC BIOCAD.Disclosure of Interests:Tatiana Korotaeva Consultant of: Pfizer, MSD, Novartis, AbbVie, Celgene, JSC BIOCAD, Janssen, UCB, Lilly and Novartis-Sandoz, Speakers bureau: Pfizer, MSD, Novartis, AbbVie, Celgene, JSC BIOCAD, Janssen, UCB, Lilly and Novartis-Sandoz, Inna Gaydukova Grant/research support from: JSC BIOCAD, Speakers bureau: Pfizer, Novartis, AbbVie, JSC BIOCAD, Сelgene, MSD, Sanofi, V Mazurov: None declared, Aleksey Samtsov Grant/research support from: JSC BIOCAD, Novartis, Eli Lilly, Johnson&Johnson, Celgene, Glenmark, Galderma, Sanofi, Vladislav Khayrutdinov Grant/research support from: Akrikhin, Alkoy, Belupo, JSC BIOCAD, Bosnaliejk, Verteks, Glenmark, Elfa, Leo Pharma, MSD, Novartis, Pfizer, Sun Pharma, Sanofi, Celgene, Pharmtec, AbbVie, Eli Lilly, Jadran, Janssen, Andrey Bakulev Grant/research support from: AbbVie, Eli Lilly, Pfizer, UCB, MSD, Novartis, Galderma, Celgene, Leo Pharma and Johnson&Johnson, JSC BIOCAD, Consultant of: Novartis, Celgene and Johnson&Johnson, Speakers bureau: AbbVie, Eli Lilly, Galderma, UCB, Novartis, Celgene and Johnson&Johnson, Muza Kokhan Grant/research support from: AbbVie, Eli Lilly, Pfizer, UCB, MSD, Novartis, Galderma, Celgene, Leo Pharma and Johnson&Johnson, JSC BIOCAD, Consultant of: Novartis, Celgene and Johnson&Johnson, Speakers bureau: AbbVie, Eli Lilly, Galderma, UCB, Novartis, Celgene and Johnson&Johnson, Alena Kundzer: None declared, Nikolaj Soroka Grant/research support from: JSC BIOCAD, Ekaterina Dokukina Employee of: JSC BIOCAD, Anna Eremeeva Employee of: JSC BIOCAD