Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used to reduce pain and inflammation, and are considered the cornerstone of pharmacological intervention in patients with radiographic axial spondyloarthritis (r-axSpA); however, the long-term use of NSAIDs is debatable due to their restricted therapeutic potential and the risk of side effects and complications. Therefore, reduction in NSAID intake is desirable in r-axSpA patients. Here, we report the long-term NSAID-sparing effect of secukinumab over 4 years in patients with r-axSpA. This post hoc analysis pooled data from 3 secukinumab trials (MEASURE 2-4) for each secukinumab maintenance dose of 150 and 300 mg, regardless of the loading dose regimen being i.v. or s.c. NSAID intake was evaluated prospectively using the Assessment of SpondyloArthritis International Society (ASAS)-NSAID score. Patients with an ASAS-NSAID score > 0 at baseline were analysed. NSAID-sparing endpoints included the mean change in the ASAS-NSAID score, the proportion of patients achieving 50% reduction, and the proportion of patients with an ASAS-NSAID score < 10. Percentages of patients who achieved BASDAI ≤ 2 were also assessed. Overall, 562 patients were included in this pooled analysis (secukinumab: 150 mg, N = 467; 300 mg, N = 95). The mean ASAS-NSAID score decreased with time in both the secukinumab 150 mg and 300 mg dose groups. The proportion of patients who achieved 50% reduction in the ASAS-NSAID score and clinically meaningful reduction of ASAS-NSAID score < 10 increased with time in both dose groups and in both low and high NSAID intake patients. The percentage of patients with a clinically relevant improvement (BASDAI ≤ 2) was consistently higher in patients with an ASAS-NSAID score < 10 than in patients with an ASAS-NSAID score ≥ 10. Secukinumab provided sustained, long-term NSAID-sparing effects in patients with r-axSpA for up to 4 years of treatment, as measured using the ASAS-NSAID score. Trial registered at clinicaltrials.gov: NCT01649375 ( https://clinicaltrials.gov/ct2/show/NCT01649375 ); NCT02008916 ( https://clinicaltrials.gov/ct2/show/NCT02008916 ); NCT02159053 ( https://clinicaltrials.gov/ct2/show/NCT02159053 ).

Altoona Center for Clinical Research Duncansville USA

Department of Rheumatology Institute of Rheumatology Prague Czech Republic

Department of Rheumatology Université de Paris Hôpital Cochin Assistance Publique Hôpitaux de Paris Paris France

INSERM Clinical Epidemiology and Biostatistics PRES Sorbonne Paris Cité Paris France

Novartis Ireland Ltd Dublin Ireland

Novartis Pharma AG Basel Switzerland

Novartis Pharmaceuticals Corporation East Hanover USA

Rheumazentrum Ruhrgebiet Herne Germany

Ruhr Universität Bochum Germany

Zobrazit více v PubMed

Sieper J, Poddubnyy D (2017) Axial spondyloarthritis. Lancet 390(10089):73–84. https://doi.org/10.1016/S0140-6736(16)31591-4 PubMed DOI

Smith JA (2015) Update on ankylosing spondylitis: current concepts in pathogenesis. Curr Allergy Asthma Rep 15(1):489. https://doi.org/10.1007/s11882-014-0489-6 PubMed DOI

Boonen A, van der Linden SM (2006) The burden of ankylosing spondylitis. J Rheumatol Suppl 78:4–11 PubMed

Bodur H, Ataman S, Rezvani A, Buğdayci DS, Cevik R, Birtane M et al (2011) Quality of life and related variables in patients with ankylosing spondylitis. Qual Life Res 20(4):543–549. https://www.jstor.org/stable/41488106

Lories RJ, Haroon N (2014) Bone formation in axial spondyloarthritis. Best Pract Res Clin Rheumatol 28(5):765–777. https://doi.org/10.1016/j.berh.2014.10.008 PubMed DOI

van der Heijde D, Ramiro S, Landewé R, Baraliakos X, Van den Bosch F, Sepriano A et al (2017) 2016 update of the ASAS-EULAR management recommendations for axial spondyloarthritis. Ann Rheum Dis 76(6):978–991. https://doi.org/10.1136/annrheumdis-2016-210770 PubMed DOI

Ward MM, Deaodhar A, Gensler LS, Dubreuil M, Yu D, Khan MA et al (2019) 2019 update of the american college of rheumatology/spondylitis association of america/spondyloarthritis research and treatment network recommendations for the treatment of ankylosing spondylitis and nonradiographic axial spondyloarthritis. Arthritis Rheumatol 71(10):1599–1613. https://doi.org/10.1002/art.41042 PubMed DOI PMC

Dougados M, Dijkmans B, Khan M, Maksymowych W, van der Linden S, Brandt J (2002) Conventional treatments for ankylosing spondylitis. Ann Rheum Dis 61(Suppl 3):iii40–iii50. https://doi.org/10.1136/ard.61.suppl_3.iii40 PubMed DOI PMC

Machado GC, Abdel-Shaheed C, Underwood M, Day RO (2021) Non-steroidal anti-inflammatory drugs (NSAIDs) for musculoskeletal pain. BMJ 372:n104. https://doi.org/10.1136/bmj.n104 PubMed DOI

Kroon F, Landewé R, Dougados M, van der Heijde D (2012) Continuous NSAID use reverts the effects of inflammation on radiographic progression in patients with ankylosing spondylitis. Ann Rheum Dis 71(10):1623–1629. https://doi.org/10.1136/annrheumdis-2012-201370 PubMed DOI

Poddubnyy D, Rudwaleit M, Haibel H, Listing J, Märker-Hermann E, Zeidler H et al (2012) Effect of non-steroidal anti-inflammatory drugs on radiographic spinal progression in patients with axial spondyloarthritis: results from the German Spondyloarthritis Inception Cohort. Ann Rheum Dis 71(10):1616–1622. https://doi.org/10.1136/annrheumdis-2011-201252 PubMed DOI

Wanders A, Heijde D, Landewé R, Béhier JM, Calin A, Olivieri I et al (2005) Nonsteroidal antiinflammatory drugs reduce radiographic progression in patients with ankylosing spondylitis: a randomized clinical trial. Arthritis Rheum 52(6):1756–1765. https://doi.org/10.1002/art.21054 PubMed DOI

Wong RSY (2019) Disease-modifying effects of long-term and continuous use of nonsteroidal anti-inflammatory drugs (NSAIDs) in Spondyloarthritis. Adv Pharmacol Sci 2019:5324170. https://doi.org/10.1155/2019/5324170 PubMed DOI PMC

Maksymowych WP (2007) Update on the treatment of ankylosing spondylitis. Ther Clin Risk Manag 3(6):1125–1133 PubMed PMC

Ward MM, Deodhar A, Gensler LS, Dubreuil M, Yu D, Khan MA et al (2019) 2019 Update of the American College of Rheumatology/Spondylitis Association of America/Spondyloarthritis Research and Treatment Network recommendations for the treatment of ankylosing spondylitis and nonradiographic axial spondyloarthritis. Arthritis Rheumatol 71(10):1599–1613. https://doi.org/10.1002/art.41042 PubMed DOI PMC

Dougados M, Wood E, Combe B, Schaeverbeke T, Miceli-Richard C, Berenbaum F et al (2014) Evaluation of the nonsteroidal anti-inflammatory drug-sparing effect of etanercept in axial spondyloarthritis: results of the multicenter, randomized, double-blind, placebo-controlled SPARSE study. Arthritis Res Ther 16(6):481–481. https://doi.org/10.1186/s13075-014-0481-5 PubMed DOI PMC

Poddubnyy D, Hermann KG, Callhoff J, Listing J, Sieper J (2014) Ustekinumab for the treatment of patients with active ankylosing spondylitis: results of a 28-week, prospective, open-label, proof-of-concept study (TOPAS). Ann Rheum Dis 73(5):817–823. https://doi.org/10.1136/annrheumdis-2013-204248 PubMed DOI

Dougados M, Simon P, Braun J, Burgos-Vargas R, Maksymowych WP, Sieper J et al (2011) ASAS recommendations for collecting, analysing and reporting NSAID intake in clinical trials/epidemiological studies in axial spondyloarthritis. Ann Rheum Dis 70(2):249–251. https://doi.org/10.1136/ard.2010.133488 PubMed DOI

Dougados M, Braun J, Szanto S, Combe B, Geher P, Leblanc V et al (2012) Nonsteroidal antiinflammatory drug intake according to the Assessment of SpondyloArthritis International Society Score in clinical trials evaluating tumor necrosis factor blockers: example of etanercept in advanced ankylosing spondylitis. Arthritis Care Res (Hoboken) 64(2):290–294. https://doi.org/10.1002/acr.20671 DOI

Marzo-Ortega H, Sieper J, Kivitz AJ, Blanco R, Cohen M, Pavelka K et al (2020) 5-year efficacy and safety of secukinumab in patients with ankylosing spondylitis: end-of-study results from the phase 3 MEASURE 2 trial. Lancet Rheumatol 2(6):e339–e346. https://doi.org/10.1016/S2665-9913(20)30066-7 DOI

Pavelka K, Kivitz A, Dokoupilova E, Blanco R, Maradiaga M, Tahir H et al (2017) Efficacy, safety, and tolerability of secukinumab in patients with active ankylosing spondylitis: a randomized, double-blind phase 3 study, MEASURE 3. Arthritis Res Ther 19(1):285. https://doi.org/10.1186/s13075-017-1490-y PubMed DOI PMC

Kivitz AJ, Wagner U, Dokoupilova E, Supronik J, Martin R, Talloczy Z et al (2018) Efficacy and safety of secukinumab 150 mg with and without loading regimen in ankylosing spondylitis: 104-week results from MEASURE 4 study. Rheumatol Ther 5(2):447–462. https://doi.org/10.1007/s40744-018-0123-5 PubMed DOI PMC

Baraliakos X, Braun J, Deodhar A, Poddubnyy D, Kivitz A, Tahir H et al (2019) Long-term efficacy and safety of secukinumab 150 mg in ankylosing spondylitis: 5-year results from the phase III MEASURE 1 extension study. RMD Open 5(2):e001005. https://doi.org/10.1136/rmdopen-2019-001005 PubMed DOI PMC

Schulz KF, Altman DG, Moher D (2010) CONSORT 2010 statement: updated guidelines for reporting parallel group randomised trials. BMJ 340:c332. https://doi.org/10.1136/bmj.c332 PubMed DOI PMC

Garrett S, Jenkinson T, Kennedy LG, Whitelock H, Gaisford P, Calin A (1994) A new approach to defining disease status in ankylosing spondylitis: the Bath Ankylosing Spondylitis Disease Activity Index. J Rheumatol 21(12):2286–2291 PubMed

van der Linden S, Valkenburg HA, Cats A (1984) Evaluation of diagnostic criteria for ankylosing spondylitis. A proposal for modification of the New York criteria. Arthritis Rheum 27(4):361–368. https://doi.org/10.1002/art.1780270401 PubMed DOI

van der Heijde D, Braun J, Dougados M, Sieper J, Pedersen R, Szumski A et al (2012) Sensitivity and discriminatory ability of the Ankylosing Spondylitis Disease Activity Score in patients treated with etanercept or sulphasalazine in the ASCEND trial. Rheumatology (Oxford) 51(10):1894–1905. https://doi.org/10.1093/rheumatology/kes142 DOI

Dougados M, Braun J, Szanto S, Combe B, Elbaz M, Geher P et al (2011) Efficacy of etanercept on rheumatic signs and pulmonary function tests in advanced ankylosing spondylitis: results of a randomised double-blind placebo-controlled study (SPINE). Ann Rheum Dis 70(5):799–804. https://doi.org/10.1136/ard.2010.139261 PubMed DOI

Torgutalp M, Poddubnyy D (2019) IL-17 inhibition in axial spondyloarthritis: current and future perspectives. Expert Opin Biol Ther 19(7):631–641. https://doi.org/10.1080/14712598.2019.1605352 PubMed DOI

Study to examine the clinical efficacy and the nonsteroidal anti-inflammatory drug (NSAID)-sparing effect of secukinumab over 16 weeks in patients with ankylosing spondylitis (ASTRUM). https://clinicaltrials.gov/ct2/show/NCT02763046 . Accessed 24 Mar 2021

Zobrazit více v PubMed

ClinicalTrials.gov
NCT01649375, NCT02008916, NCT02159053