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Diacerein for the treatment of rheumatoid arthritis in patients with inadequate response to methotrexate: a pilot randomized, double-blind, placebo-controlled add-on trial

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Abstract

Objective

To evaluate the efficacy and safety of diacerein in patients with rheumatoid arthritis (RA) who are methotrexate inadequate responders (MTX-IR).

Method

In this pilot, multicenter, double-blind, placebo-controlled trial, MTX-IR RA patients were randomized to either diacerein or matching placebo as add-on treatment to MTX for 24 weeks. Efficacy and safety were evaluated every 4 weeks until week 28. Primary and secondary efficacy endpoints were the percentage of patients achieving the ACR20 criteria and a moderate EULAR response at week 24, respectively.

Results

Forty patients were equally randomized to both study treatments; 16 and 19 participants completed the study in the diacerein and the placebo arms, respectively. Baseline characteristics were similar in both groups, except that tender joint count, DAS28-ESR score, and non-steroidal anti-inflammatory drug consumption were higher in the placebo arm. The ACR20 response at week 24 was similar in the diacerein and placebo groups (65% vs 45%, P = .20). However, treatment response according to the EULAR criteria was better in patients taking diacerein (75% vs 25% of moderate response, P = .002). In the 35 patients with assessments through week 28, diacerein was superior to placebo in ACR20 at weeks 24 and 28 (both 81% vs 47%, P = .04). Incidence of adverse events was comparable in both arms, with only chromaturia being more common with diacerein than placebo (40% vs 10%, P = .03).

Conclusions

These preliminary results show the potential benefits of diacerein on pain, joint function, and disease activity in MTX-IR RA patients.

Trial registration

ClinicalTrials.gov Identifier: NCT01264211

Key Points

• Diacerein has shown positive effects on rheumatoid arthritis symptoms.

• A good safety profile of diacerein has been observed when it was administered as add-on therapy to methotrexate in patients with rheumatoid arthritis.

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Data availability

The data generated and/or analyzed during this study are available from the corresponding author upon reasonable request.

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Acknowledgements

We thank Nuntana Kasitanon, Praveena Chiowchanwisawakit, Ajanee Mahakkanukrauh, and Parichat Ueaareewongsa who were co-investigators. Statistical analysis was performed by Statmed SARL, France. Medical writing assistance was provided by Totzke & Dreher Scientific SA, Switzerland.

Funding support

This study was supported by TRB Chemedica (Thailand) Ltd. However, the company had no influence on the design and the conduct of the study.

Author information

Authors and Affiliations

  1. Division of Rheumatology, Department of Internal Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand

    Worawit Louthrenoo

  2. Division of Rheumatology, Department of Medicine, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand

    Surasak Nilganuwong

  3. Division of Allergy Immunology and Rheumatology, Department of Medicine, Faculty of Medicine, Srinagarind Hospital, Khon Kaen University, Khon Kaen, Thailand

    Ratanavadee Nanagara

  4. Division of Rheumatology, Department of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Songkla, Thailand

    Boonjing Siripaitoon

  5. TRB Chemedica International SA, Geneva, Switzerland

    Sabine Collaud Basset

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  1. Worawit Louthrenoo
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Corresponding author

Correspondence to Worawit Louthrenoo.

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Conflict of interest

Worawit Louthrenoo and Boonjing Siripaitoon received speaking honoraria from TRB Chemedica (Thailand) Ltd. Sabine Collaud Basset is an employee of TRB Chemedica International SA, Switzerland. Surasak Nilganuwong and Ratanavadee Nanagara declared no conflicts of interest.

Patient consent

All patients gave their informed consent prior to enter the clinical trial, i.e., before they underwent any study procedure at the screening visit.

Ethics approval

The trial was conducted in accordance with the Good Clinical Practices and was compliant with the principles of the 1983 Declaration of Helsinki. Ethics approval was provided by the Institutional Review Boards of the four participating centers. The study has been registered in the ClinicalTrials.gov National Institute of Health trial register (NCT01264211).

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Louthrenoo, W., Nilganuwong, S., Nanagara, R. et al. Diacerein for the treatment of rheumatoid arthritis in patients with inadequate response to methotrexate: a pilot randomized, double-blind, placebo-controlled add-on trial. Clin Rheumatol 38, 2461–2471 (2019). https://doi.org/10.1007/s10067-019-04587-1

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  • DOI: https://doi.org/10.1007/s10067-019-04587-1

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