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Real-World Six- and Twelve-Month Drug Retention, Remission, and Response Rates of Secukinumab in 2,017 Patients With Psoriatic Arthritis in Thirteen European Countries

Real-World Six- and Twelve-Month Drug Retention, Remission, and Response Rates of Secukinumab in 2,017 Patients With Psoriatic Arthritis in Thirteen European Countries


Title: Real-World Six- and Twelve-Month Drug Retention, Remission, and Response Rates of Secukinumab in 2,017 Patients With Psoriatic Arthritis in Thirteen European Countries
Author: Michelsen, Brigitte
Georgiadis, Stylianos
Di Giuseppe, Daniela
Loft, Anne G.
Nissen, Michael J.
Iannone, Florenzo
Pombo-Suarez, Manuel
Mann, Herman
Rotar, Ziga
Eklund, Kari K.
... 23 more authors Show all authors
Date: 2022-07
Language: English
Scope: 14
University/Institute: Landspitali - The National University Hospital of Iceland
Department: Faculty of Medicine
Internal Medicine and Emergency Services
Other departments
Series: Arthritis Care and Research; 74(7)
ISSN: 2151-464X
DOI: https://doi.org/10.1002/acr.24560
Subject: Gigtarlæknisfræði; Vísindadeild; Sóríasis; Antibodies, Monoclonal, Humanized; Antirheumatic Agents; Arthritis, Psoriatic; Humans; Interleukin-17; Treatment Outcome; Rheumatology
URI: https://hdl.handle.net/20.500.11815/3330

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Citation:

Michelsen , B , Georgiadis , S , Di Giuseppe , D , Loft , A G , Nissen , M J , Iannone , F , Pombo-Suarez , M , Mann , H , Rotar , Z , Eklund , K K , Kvien , T K , Santos , M J , Gudbjornsson , B , Codreanu , C , Yilmaz , S , Wallman , J K , Brahe , C H , Möller , B , Favalli , E G , Sánchez-Piedra , C , Nekvindova , L , Tomsic , M , Trokovic , N , Kristianslund , E K , Santos , H , Löve , T J , Ionescu , R , Pehlivan , Y , Jones , G T , van der Horst-Bruinsma , I , Ørnbjerg , L M , Østergaard , M & Hetland , M L 2022 , ' Real-World Six- and Twelve-Month Drug Retention, Remission, and Response Rates of Secukinumab in 2,017 Patients With Psoriatic Arthritis in Thirteen European Countries ' , Arthritis Care and Research , vol. 74 , no. 7 , pp. 1205-1218 . https://doi.org/10.1002/acr.24560

Abstract:

Objective: There is a lack of real-life studies on interleukin-17 (IL-17) inhibition in psoriatic arthritis (PsA). We assessed real-life 6- and 12-month effectiveness (i.e., retention, remission, low disease activity [LDA], and response rates) of the IL-17 inhibitor secukinumab in PsA patients overall and across 1) number of prior biologic/targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs), 2) years since diagnosis, and 3) European registries. Methods: Thirteen quality registries in rheumatology participating in the European Spondyloarthritis Research Collaboration Network provided longitudinal, observational data collected as part of routine care for secondary use. Data were pooled and analyzed with Kaplan-Meier plots, log rank tests, Cox regression, and multiple linear and logistic regression analyses. Results: A total of 2,017 PsA patients started treatment with secukinumab between 2015 and 2018. Overall secukinumab retention rates were 86% and 76% after 6 and 12 months, respectively. Crude (LUNDEX adjusted) 6-month remission/LDA (LDA including remission) rates for the 28-joint Disease Activity Index for Psoriatic Arthritis, the Disease Activity Score in 28 joints using the C-reactive protein level, and the Simplified Disease Activity Index (SDAI) were 13%/46% (11%/39%), 36%/55% (30%/46%), and 13%/56% (11%/47%), and 12-month rates were 11%/46% (7%/31%), 39%/56% (26%/38%), and 16%/62% (10%/41%), respectively. Clinical Disease Activity Index remission/LDA rates were similar to the SDAI rates. Six-month American College of Rheumatology 20%/50%/70% improvement criteria responses were 34%/19%/11% (29%/16%/9%); 12-month rates were 37%/21%/11% (24%/14%/7%). Secukinumab effectiveness was significantly better for b/tsDMARD-naive patients, similar across time since diagnosis (<2/2–4/>4 years), and varied significantly across the European registries. Conclusion: In this large real-world study on secukinumab treatment in PsA, 6- and 12-month effectiveness was comparable to that in previous observational studies of tumor necrosis factor inhibitors. Retention, remission, LDA, and response rates were significantly better for b/tsDMARD-naive patients, were independent of time since diagnosis, and varied significantly across the European countries.

Description:

Funding Information: The EuroSpA collaboration was financially supported by Novartis. Novartis had no influence on the data collection, statistical analyses, manuscript preparation, or decision to submit. Funding Information: Novartis had no role in the study design or in the collection, analysis, or interpretation of the data, the writing of the manuscript, or the decision to submit the manuscript for publication. Publication of this article was not contingent upon approval by Novartis. This large real-life study of secukinumab effectiveness (i.e., drug retention, remission, LDA, and response rates) included 2,017 patients with PsA treated as part of routine care in 13 countries across Europe. Overall, high 6-month (86%) and 12-month (76%) secukinumab retention rates were found. Secukinumab effectiveness was significantly better for biologics-naive patients after 6 as well as 12 months of treatment, was independent of time since diagnosis, and differed significantly across the European countries. Remission, LDA, and response rates were overall comparable to previous real-life observations in patients treated with a TNFi (5). Hence, this large observational study documents the effectiveness of secukinumab in the treatment of PsA patients. Secukinumab effectiveness has previously been reported in one observational study of 76 Spanish PsA patients, in which 12-month retention rates were somewhat higher than in our study; for biologics-naive patients, it was 91%, and for non-naive patients, it was 82% (22). Good 1-year secukinumab effectiveness has also been reported in an Italian observational study of 130 PsA patients (23). In the FUTURE 1 RCT, 89% of the patients in the 150-mg secukinumab group reached 52 weeks, and ACR20/50 responses at week 24 and 52 were achieved by 50%/35% and 60%/43% of the patients, respectively (24). In our observational study, ACR20/50 responses at week 26 and 52 were lower than in the FUTURE 1 study (34%/19% and 37%/21%), probably reflecting that the study designs differed substantially (longitudinal observational study with 22% biologics-naive patients versus RCT with 71% biologics-naive patients). In the FUTURE 5 RCT, 91% of the patients treated with 150 mg of secukinumab completed 52 weeks of treatment, with ACR20/50/70 responses of 64%/41%/26%, thus substantially higher than in our study (10). Interestingly, the overall secukinumab retention rates in this real-life study were similar to the retention rates of TNFi in a recently published observational study of 14,261 European biologics-naive PsA patients (86% versus 86% at 6 months; 76% versus 77% at 12 months, respectively) and numerically slightly higher for biologics-naive secukinumab than TNFi starters (90% versus 86% at 6 months, and 82% versus 77% at 12 months, respectively) (5). Overall, remission and response rates for patients treated with secukinumab were fairly similar to what was reported for TNFi (5) as well as to the effectiveness of TNFi reported in other, smaller observational studies (25–28). Similar to findings in observational studies on TNFi, and in the FUTURE 2 and 5 trials, the current study demonstrated that effectiveness of secukinumab declines with increasing previous use of b/tsDMARDs, possibly reflecting confounding by indication (9,27,29,30). The similar secukinumab effectiveness for patients with different disease durations found in this study is also in accordance with previous findings for TNFi in patients with PsA (31–33). In the 2017 updated treat-to-target recommendations for PsA, the DAPSA and minimal disease activity (MDA) are the preferred measures to define treatment target in PsA patients (34). In our study, the DAPSA (including a 66 swollen/68 tender joint count) (35) was only available in a minority of patients. Instead, we used the DAPSA28, which only requires a 28-joint count (13). The DAPSA28 has shown good criterion, correlational, and construct validity, as well as sensitivity to change, although the original DAPSA should be preferred when available (13). MDA was not assessed in the study due to lack of data on enthesitis and psoriasis in the majority of registries. We chose the DAS28-CRP over the DAS28-ESR due to less missing data for the DAS28-CRP. Overall, the DAS28-CRP was a more liberal remission criterion than the SDAI, the CDAI, and the DAPSA28 in our study, which is consistent with previous reports (5,12,36,37). In the DAPSA28, SDAI, and CDAI LDA measures, we chose to include remission in accordance with the DAS28 LDA, as we believe that rheumatologists will be mainly interested in knowing how many patients at least were in LDA (i.e., in LDA or remission). The major strength of this study is the 12-month longitudinal, observational study design with inclusion of a high number of PsA patients from 13 different countries. Furthermore, the data included in the study were collected independently of commercial interests as part of standard care. Hence, although Novartis supports the EuroSpA collaboration, Novartis had no influence on data collection, statistical analyses, manuscript preparation, or the decision to submit. Major limitations of the study include lack of data on extraarticular inflammatory involvement and the fact that data on the optimal number of joints (66/68) were generally not available, which may have led to underestimation of disease activity. Furthermore, the DAS28, the CDAI, and the SDAI are composite scores originally developed for RA and not PsA. Heterogeneity in baseline characteristics and secukinumab effectiveness across the registries was found. Importantly, the number of included patients (from 30 to 657) and proportions of biologics-naive patients (from 5% to 97%) varied considerably across the registries and may explain some of the heterogeneity in effectiveness measures, e.g., a higher proportion of biologics-naive patients may positively impact upon treatment outcomes. Moreover, low patient numbers in some registries will lead to more uncertain estimates, i.e., single patients will have a higher influence on outcomes. Also, the influence of different treatment guidelines and access to treatment in the different European countries were not accounted for in this study. Hence, interpretation of the pooled analyses should be done with caution. Of note, however, consistent results in prespecified unadjusted and adjusted analyses were found. Furthermore, as is often the case in observational studies, some missing data on disease states and response rates were observed, challenging the generalizability of the findings. However, the study is by far the largest real-life study to date on secukinumab effectiveness in patients with PsA. In conclusion, in this longitudinal observational study of >2,000 patients with PsA treated with secukinumab, we found high retention rates after 6 and 12 months of treatment and good remission, LDA, and response rates. Secukinumab effectiveness was significantly better for biologics-naive patients, was independent of time since diagnosis, and varied across European registries. Funding Information: Dr. Michelsen has received consulting fees from Novartis (less than $10,000) and research support from Novartis. Dr. Georgiadis has received research support from Novartis. Dr. Loft has received consulting fees and/or speaking fees from AbbVie, Eli Lilly and Company, Janssen, MSD, Novartis, Pfizer, and UCB (less than $10,000 each). Dr. Nissen has received consulting fees and/or speaking fees from AbbVie, Celgene, Eli Lilly and Company, Novartis, and Pfizer (less than $10,000 each). Dr. Iannone has received consulting fees and/or speaking fees from AbbVie, Eli Lilly and Company, MSD, Novartis, Pfizer, Roche, Janssen, Bristol Myers Squibb, and Sanofi (less than $10,000 each). Dr. Rotar has received consulting fees and/or speaking fees from AbbVie, Amgen, Biogen, Eli Lilly and Company, Medis, MSD, Novartis, Pfizer, and Sanofi (less than $10,000 each). Dr. Kvien has received consulting fees and/or speaking fees from AbbVie, Amgen, Biogen, Celltrion, Egis, Eli Lilly and Company, Eva Pharma, Ewopharma, Gilead, Hikma, MSD, Mylan, Novartis/Sandoz, Oktal, Orion Pharma, Hospira/Pfizer, Roche, Sanofi, and UCB (less than $10,000 each) and research support to Diakonhjemmet Hospital from AbbVie, Bristol Myers Squibb, MSD, Pfizer, Roche, and UCB. Dr. Santos has received speaking fees from AbbVie, Novartis, Pfizer, and Roche (less than $10,000 each). Dr. Gudbjornsson has received speaking fees from Novartis (less than $10,000). Dr. Codreanu has received consulting fees and/or speaking fees from AbbVie, Accord Healthcare, Alfasigma, Egis, Eli Lilly and Company, Ewopharma, Genesis, Mylan, Novartis, Pfizer, Roche, Sandoz, and UCB (less than $10,000 each). Dr. Wallman has received consulting fees from Celgene, Eli Lilly and Company, and Novartis (less than $10,000 each). Dr. Brahe has received research support from Novartis. Dr. Favalli has received consulting fees and/or speaking fees from AbbVie, Bristol Myers Squibb, Eli Lilly and Company, UCB Novartis, Pfizer, and Sanofi‐Genzyme (less than $10,000 each). Dr. Ionescu has received consulting fees and/or speaking fees from AbbVie, Amgen, Eli Lilly and Company, Ewopharma, Novartis/Sandoz, Pfizer, Roche, and UCB (less than $10,000 each). Dr. Jones has received research support from AbbVie, Pfizer, UCB, Amgen, and GlaxoSmithKline. Dr. van der Horst‐Bruinsma has received consulting fees and/or speaking fees from AbbVie, Eli Lilly and Company, Novartis, UCB, Bristol Myers Squibb, MSD, UCB, and Pfizer (less than $10,000 each). Dr. Ørnbjerg has received research support from Novartis. Dr. Østergaard has received consulting fees and/or speaking fees from AbbVie, Bristol Myers Squibb, Boehringer‐Ingelheim, Celgene, Eli Lilly and Company, Hospira, Janssen, Merck, Novartis, Novo, Orion, Pfizer, Regeneron, Roche, Sandoz, Sanofi, and UCB (less than $10,000 each) and research support from AbbVie, Bristol Myers Squibb, Celgene, Merck, and Novartis. Dr. Hetland has received consulting fees and/or speaking fees from Eli Lilly and Company, Orion Pharma, Biogen, Pfizer, CellTrion, Merck, and Samsung Bioepis (less than $10,000 each) and research support from Bristol Myers Squibb, MSD, AbbVie, Roche, Novartis, Biogen, and Pfizer. No other disclosures relevant to this article were reported. Publisher Copyright: © 2021 The Authors. Arthritis Care & Research published by Wiley Periodicals LLC on behalf of American College of Rheumatology.

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