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Tocilizumab in patients with new onset polymyalgia rheumatica (PMR-SPARE): a phase 2/3 randomised controlled trial
  1. Michael Bonelli1,
  2. Helga Radner1,
  3. Andreas Kerschbaumer1,
  4. Daniel Mrak1,
  5. Martina Durechova1,
  6. Jutta Stieger2,
  7. Rusmir Husic3,
  8. Peter Mandl1,
  9. Josef S Smolen1,
  10. Christian Dejaco3,4,
  11. Daniel Aletaha1
  1. 1 Division of Rheumatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
  2. 2 2nd Department of Medicine, Hietzing Hospital, Vienna, Austria
  3. 3 Department of Rheumatology, Medical University of Graz, Graz, Austria
  4. 4 Rheumatology, Brunico Hospital, Brunico, Italy
  1. Correspondence to Professor Daniel Aletaha, Division of Rheumatology, Medical University of Vienna, Vienna, Austria; daniel.aletaha{at}meduniwien.ac.at

Abstract

Background Polymyalgia rheumatica is the second most common inflammatory rheumatic disease of people >50 years. Glucocorticoid therapy is highly effective, but many patients require treatment for several years. Effective glucocorticoid sparing agents are still needed.

Methods In this double-blind, multi-centre phase 2/3 clinical trial, we randomly assigned 36 patients with new onset polymyalgia rheumatica from three centres to receive subcutaneous tocilizumab (162 mg per week) or placebo for 16 weeks (1:1 ratio). All patients received oral prednisone, tapered from 20 mg to 0 mg over 11 weeks.

The primary endpoint was the proportion of patients in glucocorticoid-free remission at week 16; key secondary endpoints, including time to first relapse and cumulative glucocorticoid dose at weeks 16 and 24, were evaluated.

Results From 20 November 2017 to 28 October 2019 39 patients were screened for eligibility; 19 patients received tocilizumab and 17 placebo. Glucocorticoid-free remission at week 16 was achieved in 12 out of 19 patients on tocilizumab (63.2%) and 2 out of 17 patients receiving placebo (11.8%, p=0.002), corresponding to an OR of 12.9 (95 % CI: 2.2 to 73.6) in favour of tocilizumab. Mean (±SD) time to first relapse was 130±13 and 82±11 days (p=0.007), respectively, and the median (IQR) cumulative glucocorticoid dose was 727 (721–842) mg and 935 (861–1244) mg (p=0.003), respectively. Serious adverse events were observed in five placebo patients and one tocilizumab patient.

Conclusion In patients with new onset polymyalgia rheumatica undergoing rapid glucocorticoid tapering, tocilizumab was superior to placebo regarding sustained glucocorticoid-free remission, time to relapse and cumulative glucocorticoid dose.

Trial registration number NCT03263715

  • polymyalgia rheumatica
  • glucocorticoids
  • antirheumatic agents

Data availability statement

Anonymous participant data are available under specific conditions. Proposals will be reviewed and approved by the sponsor, scientific committee and staff on the basis of scientific merit and absence of competing interests. Once the proposal has been approved, data can be transferred through a secure online platform after the signing of a data access agreement and a confidentiality agreement. Not applicable.

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Data availability statement

Anonymous participant data are available under specific conditions. Proposals will be reviewed and approved by the sponsor, scientific committee and staff on the basis of scientific merit and absence of competing interests. Once the proposal has been approved, data can be transferred through a secure online platform after the signing of a data access agreement and a confidentiality agreement. Not applicable.

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Footnotes

  • Handling editor David S Pisetsky

  • Contributors DA, JSS and CD were responsible for the study design. HR and AK were responsible for data analysis. MB, DA, JSS, HR and CD were responsible for writing of the manuscript. MD, JS, RH, MB, AK, DM, PM and DA were responsible for recruitment and clinical care of patients. HR, AK, MD, MB and DA accessed and verified the data. All authors had full access to all the data in the study and had final responsibility for the decision to submit for publication. All authors reviewed and approved the final version of the manuscript. DA accepts full responsibility for the work and/or the conduct of the study, had access to the data and controlled the decision to publish.

  • Funding The study was sponsored by the Medical University Vienna who received an unrestricted grant from Roche, the manufacturer of tocilizumab, who provided study drug and matching placebo. The funder reviewed and approved the study protocol, but had subsequently no role in conduct of the study including data collection, data analysis, data interpretation or writing of the report.

  • Competing interests AK reports about contracts and personal fees from AbbVie, Bristol Myers Squibb, Celgene, Eli Lilly, Gilead, Merck Sharp and Dohme. RH reports about personal fees from MSD, AbbVie, Pfizer, Lilly, Bristol Myers Squibb, Celgene and Novartis. MB reports about personal fees from Eli Lilly. PM reports speaker fees from AbbVie, Janssen and Novartis and research grants from AbbVie, BMS, Novartis, Janssen, MSD and UCB. MB reports about personal fees from Eli Lilly. DA reports about financial support from Roche to perform this study for the Department of Rheumatology. DA received grants and consulting fees from AbbVie, Amgen, Lilly, Merck, Novartis, Pfizer, Roche and Sandoz. CD received grants, consulting and personal fees from Celgene, Roche, Sanofi, AbbVie, Janssen, Roche, Novartis and Pfizer. JS reports about grants, consulting and personal fees from AbbVie, AstraZeneca, Lilly, Novartis, Amgen, Astro, Bristol Myers Squibb, Celgene, Celltrion, Chugai, Gilead, ILTOO, Janssen, Merck Sharp & Dohme, Novartis-Sandoz, Pfizer, Roche, Samsung and UCB. All other authors declare no competing interests. DA and JS declare that they currently have active roles as editorial board members of the journal.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.

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