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Nonsteroidal anti-inflammatory drug-sparing effect of secukinumab in patients with radiographic axial spondyloarthritis: 4-year results from the MEASURE 2, 3 and 4 phase III trials

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Abstract

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).

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Availability of data and material

The datasets used and/or analysed during the current study are available from the corresponding author upon reasonable request.

Data sharing statement

The datasets generated and/or analysed during the current study are not publicly available. Novartis is committed to sharing with qualified external researchers’ access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved based on scientific merit. All data provided are anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. The data may be requested from the corresponding author of the manuscript.

Abbreviations

ACR:

American College of Rheumatology

ASAS:

Assessment of SpondyloArthritis International Society

axSpA:

Axial spondyloarthritis

BASDAI:

Bath Ankylosing Spondylitis Disease Activity Index

bDMARDs:

Biologic disease-modifying antirheumatic drugs

EULAR:

European League Against Rheumatism

i.v.:

Intravenous

IL-17A:

Interleukin-17A

NSAIDs:

Nonsteroidal anti-inflammatory drugs

q4w:

Every 4 weeks

r-axSpA:

Radiographic axial spondyloarthritis

RCT:

Randomised clinical trial

s.c.:

Subcutaneous

SpA:

Spondyloarthritis

TNFi:

Tumour necrosis factor inhibitors

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Acknowledgements

The authors thank the patients who participated in this study; the study investigators and John Gallagher, Novartis Pharmaceuticals UK Limited for the valuable review. Manuscript writing support, under the guidance of all authors, was provided by Priyanka Malla and Md Zuber Birajdar, Novartis Healthcare Pvt. Ltd, Hyderabad, India.

Funding

This study was funded by Novartis Pharma AG, Basel, Switzerland.

Author information

Authors and Affiliations

  1. Department of Rheumatology, Université de Paris, Hôpital Cochin, Assistance Publique-Hôpitaux de Paris, Paris, France

    Maxime Dougados

  2. INSERM (U1153): Clinical Epidemiology and Biostatistics, PRES Sorbonne Paris-Cité, Paris, France

    Maxime Dougados

  3. Rheumazentrum Ruhrgebiet, Herne, Germany

    Uta Kiltz

  4. Ruhr Universität, Bochum, Germany

    Uta Kiltz

  5. Altoona Center for Clinical Research, Duncansville, USA

    Alan Kivitz

  6. Department of Rheumatology, Institute of Rheumatology, Prague, Czech Republic

    Karel Pavelka

  7. Novartis Pharma AG, Basel, Switzerland

    Susanne Rohrer & Erhard Quebe-Fehling

  8. Novartis Ireland Ltd, Dublin, Ireland

    Suzanne McCreddin

  9. Novartis Pharmaceuticals Corporation, East Hanover, USA

    Brian Porter & Zsolt Talloczy

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  1. Maxime Dougados
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Contributions

All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship of this article, take responsibility for the integrity of the work as a whole, were involved in the drafting and critical review of the manuscript and approved the final version for submission. All authors agree to be accountable for all aspects of the work and attest to the accuracy and integrity of the work.

Corresponding author

Correspondence to Maxime Dougados.

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Conflict of interest

MD: Grant/research support from: AbbVie, Eli Lilly, Merck, Novartis, Pfizer and UCB Pharma, Consultant of: AbbVie, Eli Lilly, Merck, Novartis, Pfizer and UCB Pharma, Speakers bureau: AbbVie, Eli Lilly, Merck, Novartis, Pfizer and UCB Pharma. UK: Grant/research support from: AbbVie, Amgen, Biogen, Hexal, Novartis, Pfizer, Consultant of: AbbVie, Eli Lilly and Company, Hexal, Janssen, Novartis, Pfizer, UCB, Speakers bureau: AbbVie, MSD, Novartis, Pfizer, Roche, UCB. AK: Shareholder of: AbbVie, Amgen, Gilead, GSK, Pfizer Inc, Sanofi, Consultant of: AbbVie, Boehringer Ingelheim, Flexion, Genzyme, Gilead, Janssen, Novartis, Pfizer Inc, Regeneron, Sanofi, SUN Pharma Advanced Research, UCB, Paid instructor for: Celgene, Genzyme, Horizon, Merck, Novartis, Pfizer, Regeneron, Sanofi, Speakers bureau: AbbVie, Celgene, Flexion, Genzyme, Horizon, Merck, Novartis, Pfizer Inc, Regeneron, Sanofi. KP: Speakers bureau: AbbVie, BMS, MSD, UCB, Medac, Egis, Pfizer, Roche, Biogen, Novartis. SR, SM, EQF, BP, ZS: Employee and shareholder of Novartis.

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This study was conducted in accordance with the principles of the Declaration of Helsinki and all centers received approval from independent ethics committees or institutional review boards.

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Dougados, M., Kiltz, U., Kivitz, A. et al. Nonsteroidal anti-inflammatory drug-sparing effect of secukinumab in patients with radiographic axial spondyloarthritis: 4-year results from the MEASURE 2, 3 and 4 phase III trials. Rheumatol Int 42, 205–213 (2022). https://doi.org/10.1007/s00296-021-05044-6

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