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  • Changes in patient characteristics in anti-tumour necrosis factor clinical trials for rheumatoid arthritis: results of an analysis of the literature over the past 16 years

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Clinical and epidemiological research
Extended report
Changes in patient characteristics in anti-tumour necrosis factor clinical trials for rheumatoid arthritis: results of an analysis of the literature over the past 16 years
  1. Mahboob U Rahman1,2,3,
  2. Jacqui Buchanan4,5,
  3. Mittie K Doyle1,2,
  4. Elizabeth C Hsia1,2,
  5. Timothy Gathany4,
  6. Shreekant Parasuraman4,
  7. Daniel Aletaha6,
  8. Eric L Matteson7,
  9. Philip G Conaghan8,
  10. Edward Keystone9,
  11. Désireé van der Heijde10,
  12. Josef S Smolen6
  1. 1Centocor R&D, Inc, Malvern, Pennsylvania, USA
  2. 2University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA
  3. 3*Pfizer, Inc, Collegeville, Pennsylvania, USA
  4. 4Johnson & Johnson Pharmaceutical Services, Malvern, Pennsylvania, USA
  5. 5*Buchanan Biotech Consulting, Mountain View, California, USA
  6. 6Medical University of Vienna and Hietzing Hospital, Vienna, Austria
  7. 7Mayo Clinic, Rochester, Minnesota, USA
  8. 8NIHR Leeds Musculoskeletal Biomedical Research Unit, University of Leeds, Leeds, UK
  9. 9University of Toronto, Toronto, Ontario, Canada
  10. 10Leiden University Medical Center, Leiden, The Netherlands
  1. Correspondence toJosef S Smolen, Division of Rheumatology, Department of Internal Medicine III, Medical University of Vienna and The Center for Rheumatic Diseases, Hietzing Hospital, Vienna A-1090, Austria; josef.smolen{at}wienkav.at

Abstract

Objective To evaluate changes in baseline patient characteristics and entry criteria of randomised, controlled studies of tumour necrosis factor alpha (TNFα) inhibitors in rheumatoid arthritis (RA) patients.

Methods A systematic literature review was performed using predefined inclusion criteria to identify randomised, double-blind, controlled trials that evaluated TNFα inhibitors in adult RA patients. Entry criteria and baseline clinical characteristics were evaluated over time for methotrexate-experienced and methotrexate-naive study populations. Enrolment start date for each trial was the time metric. The anchor time was the study with the earliest identifiable enrolment start date.

Results 44 primary publications (reporting the primary study endpoint) from 1993 to 2008 met the inclusion criteria. Enrolment start dates of August 1993 and May 1997 were identified as time anchors for the 37 methotrexate-experienced studies and the seven methotrexate-naive studies, respectively. In methotrexate-experienced trials, no significant change was observed over the years included in this study in any inclusion criteria (including swollen joint counts and C-reactive protein (CRP)), but a significant decrease over time was observed in the baseline swollen joint count, CRP and total Sharp or van der Heijde modified Sharp score, but not in baseline tender joint counts. In the methotrexate-naive studies, significant decreases over the years were observed in swollen joint and tender joint inclusion criteria, but not in baseline tender joint count, baseline CRP, CRP inclusion criteria or baseline total Sharp or van der Heijde modified Sharp score.

Conclusion Inclusion criteria and baseline characteristics of RA patients enrolled in studies of TNFα inhibitors have changed, with more recent trials enrolling cohorts with lower disease activity, especially in methotrexate-experienced trials.

This paper is freely available online under the BMJ Journals unlocked scheme, see http://ard.bmj.com/info/unlocked.dtl

https://doi.org/10.1136/ard.2010.146043

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    Footnotes

    • ↵* Current affiliation of the author

    • Funding This study was funded by Johnson & Johnson.

    • Competing interests MUR, JB, MKD, ECH, TG and SP were all employees of Johnson & Johnson at the time of the study and own Johnson & Johnson stock options. ELM has been a paid consultant and advisory board member and is an investigator for Johnson & Johnson/Centocor. PGC has received consulting fees, speaking fees and/or research grants from Astra Zeneca, Bristol-Myers Squibb, Centocor; Merck, Sharpe and Dohme, Novartis, Roche and Pfizer. EK has received funding research from Abbot Laboratories, Amgen, AstraZeneca Pharmaceuticals LP, Bristol-Myers Squibb, Centocor, F. Hoffman-LaRoche, Novartis Pharmaceuticals Schering-Plough Corporation, UCB and Wyeth Pharmaceuticals. He has consulting agreements/advisory board memberships with Abbott Laboratories, Amgen, Bristol-Myers Squibb Company, Centocor, F. Hoffman-LaRoche, Genentech, Schering-Plough Corporation, UCB and Pfizer Pharmaceuticals. He has speaker honoraria agreements with Abbott Laboratories, Amgen, Bristol-Myers Squibb Company, F. Hoffman-LaRoche, Schering-Plough Corporation and Pfizer Pharmaceuticals. JSS has received grant support from and/or provided expert advice to Abbott, Amgen, BMS, Centocor, MSD, Pfizer, Roche, UCB and Sanofi-Aventis. DA and DvdH have nothing to declare.

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