Article Text

PDF

Response to: ‘Some concerns from Turkey’ by Bilgin et al
  1. Yuko Kaneko1,
  2. Hideto Kameda1,2,
  3. Kei Ikeda3,
  4. Tomonori Ishii4,
  5. Kosaku Murakami5,
  6. Hyota Takamatsu6,
  7. Yoshiya Tanaka7,
  8. Takayuki Abe8,
  9. Tsutomu Takeuchi1
  1. 1 Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan
  2. 2 Division of Rheumatology, Department of Internal Medicine, Toho University Ohashi Medical Center, Tokyo, Japan
  3. 3 Department of Allergy and Clinical Immunology, Chiba University Hospital, Chiba, Japan
  4. 4 Department of Hematology and Rheumatology, Tohoku University Graduate School of Medicine, Sendai, Japan
  5. 5 Department of Rheumatology and Clinical Immunology, Kyoto University, Kyoto, Japan
  6. 6 Department of Respiratory Medicine and Clinical Immunology, Graduate School of Medicine, Osaka University, Osaka, Japan
  7. 7 The First Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan
  8. 8 Department of Preventive Medicine and Public Health, Biostatistics at Clinical and Translational Research Center, Keio University School of Medicine, Tokyo, Japan
  1. Correspondence to Professor Tsutomu Takeuchi, Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo 160-8582, Japan; tsutake{at}z5.keio.jp

Statistics from Altmetric.com

We would like to thank Bilgin et al 1 for their interest in our paper2 and asking several questions for clarification.

First, we allowed non-steroidal anti-inflammatory drugs (NSAIDs) in this trial, except for the 6 weeks (from 2 weeks prior to the initiation of trial drugs until 4 weeks) during which NSAIDs were allowed only for fever, in order to assess the status of body temperature appropriately.

Second, the per cent change in glucocorticoid dose were compared between the placebo and tocilizumab groups by means of analysis of covariance model with group as a factor and baseline as a covariate. Therefore, least squares means adjusted for baseline imbalance were presented in our manuscript, which are not consistent with simple summary statistics. We chose this model (not non-parametric one) because of its robustness in terms of the deviation from the normality assumption even with small sample size and prespecified this linear model in statistical analysis plan before the unblinding. We also confirmed that there were no outliers in our data to ensure the appropriateness of the analysis plan.

Third, the primary analysis population for efficacy evaluation in the double-blind phase (parts 1 and 2) was full analysis set, which consisted of patients who received at least one dose of the study medication. Therefore, all randomised patients, except for one patient in the placebo group whose underlying disease turned out to be lymphoma, not adult-onset Still’s disease, were included in efficacy analyses. This is consistent with the intention-to-treat principle. The criteria for escape during part 2 in our trial was non-achievement of American College of Rheumatology (ACR) 50 without fever under the initial dose of glucocorticoids while the endpoint at week 12 was ACR50 achievement.

Finally, as Bilgin et al pointed out, patients who received placebo had worse disease activity and took higher doses of glucocorticoids, and the efficacy outcomes in the placebo group were better than had been expected. This might be owing to careful patient enrollment or the effectiveness of slightly higher dose of predonisolone in the placebo group. However, this was the first trial using placebo in patients with adult-onset Still’s disease, and considering occasional fatal clinical courses of the disease, the investigators were compelled to be cautious.

We totally agree with Bilgin et al that establishing more sophisticated, validated tools or scoring systems is essential in trials and the management of adult-onset Still’s disease.

References

View Abstract

Footnotes

  • Handling editor Josef S Smolen

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Patient consent Not required.

  • Provenance and peer review Commissioned; internally peer reviewed.

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

Linked Articles

  • Correspondence
    Emre Bilgin İrem Ozarli Levent Kılıç Ertuğrul Çağrı Bölek Gözde Kübra Yardımcı Ömer Karadağ