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Results of a phase-I/II randomized, masked, placebo-controlled trial of recombinant human interleukin-11 (rhIL-11) in the treatment of subjects with active rheumatoid arthritis

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Abstract

Interleukin-11 (IL-11) is a pleiotropic cytokine that regulates the growth and development of hematopoietic stem cells and decreases the proinflammatory mediators of cytokine and nitric oxide production. In animal models of arthritis, treatment with recombinant human IL-11 (rhIL-11) reduces both the level of synovitis and the histologic lesion scores in the joints.

The goal of this phase-I/II study in adults with rheumatoid arthritis (RA) was to evaluate the safety and clinical activity of different doses and schedules of rhIL-11 in patients with active RA for whom treatment with at least one disease-modifying antirheumatic drug had failed.

This was a multicenter, randomized, placebo-controlled trial that evaluated the safety and tolerability of rhIL-11 in 91 patients with active RA. rhIL-11 was administered subcutaneously; patients were randomized into one of five treatment groups (ratio of rhIL-11 to placebo, 4:1). Patients were treated for 12 weeks with either 2.5 or 7.5 μg/kg of rhIL-11 or placebo twice per week or 5 or 15 μg/kg of rhIL-11 or placebo once per week. The status of each subject's disease activity in accordance with the American College of Rheumatology (ACR) criteria was assessed before, during, and after completion of administration of the study drug.

Administration of rhIL-11 was well tolerated at all doses and schedules. The most frequent adverse event was a reaction at the injection site. The data suggest a statistically significant reduction in the number of tender joints (P < 0.008) at the 15 μg/kg once-weekly dose schedule but showed no overall significant benefit at the ACR criterion of a 20% response.

The trial showed rhIL-11 to be safe and well tolerated at a variety of doses and schedules over a 12-week treatment period in patients with active RA. The only adverse event clearly associated with rhIL-11 administration was reaction at the injection site.

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Abbreviations

ACR:

American College of Rheumatology

CRP:

C-reactive protein

DMARD:

disease-modifying antirheumatic drug

IL:

interleukin

NF:

nuclear factor

RA:

rheumatoid arthritis

rhIL-11:

recombinant human IL-11

TNF:

tumor necrosis factor.

References

  1. Trepecchio WL, Bozza M, Pednault G, Dorner AJ: Recombinant human IL-11 attenuates the inflammatory response through down-regulation of proinflammatory cytokine release and nitric oxide production. J Immunol. 1996, 157: 3627-3634.

    Google Scholar 

  2. Leng SX, Elias JA: Interleukin-11 inhibits macrophage interleukin-12 production. J Immunol. 1997, 159: 2161-2168.

    PubMed  CAS  Google Scholar 

  3. Hermann JA, Hall MA, Maini RN, Feldmann M, Brennan F: Important immunoregulatory role of interleukin-11 in the inflammatory process in rheumatoid arthritis. Arthritis Rheum. 1998, 41: 1388-97. 10.1002/1529-0131(199808)41:8<1388::AID-ART7>3.0.CO;2-F.

    Article  PubMed  CAS  Google Scholar 

  4. Trepecchio WL, Wang L, Bozza M, Dorner AJ: IL-11 regulates macrophange effector function through inhibition of nuclear factor-κB. J Immunol. 1997, 159: 5661-5670.

    Google Scholar 

  5. Walmsley M, Butler DM, Marinova-Mutafchieva L, Feldmann M: An anti-inflammatory role for interleukin-11 in established murine collagen-induced arthritis. Immunology. 1998, 95: 31-37. 10.1046/j.1365-2567.1998.00568.x.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  6. Hochberg MC, Spector TD: Epidemiology of rheumatoid arthritis: update. Epidemiol Rev. 1990, 12: 247-252.

    PubMed  CAS  Google Scholar 

  7. Ferraccioli G, Salaffi F, Nervetti A, Cavalieri F: Slow-acting drugs - outcome is no different than 15 years ago. J Rheumatol. 1990, 17: 1249-1250.

    PubMed  CAS  Google Scholar 

  8. Moreland L, Heck L, Koopman W: Biologic agents for treating rheumatoid arthritis. Arthritis Rheum. 1997, 40: 397-409.

    Article  PubMed  CAS  Google Scholar 

  9. Thorton SC, Por SB, Penny R, Richter M, Shelley L, Breit SN: Identification of the major fibroblast growth factors released spontaneously in inflammatory arthritis as platelet derived growth factor and tumor necrosis factor-alpha. Clin Exp Immunol. 1991, 86: 79-86.

    Article  Google Scholar 

  10. Beckham JC, Caldwell DS, Peterson BL, Pippen AM, Currie MS, Keefe FJ, Weinberg JB: Disease severity in rheumatoid arthritis: relationships of plasma tumor necrosis factor-alpha, soluble interleukin 2-receptor, soluble CD4/CD8 ratio, neopterin, and fibrin D-dimer to traditional severity and functional measures. J Clin Immunol. 1992, 12: 353-361.

    Article  PubMed  CAS  Google Scholar 

  11. Moreland LW, Schiff MH, Baumgartner SW, Tindall EA, Fleischmann RM, Bulpitt KJ, Weaver AL, Keystone EC, Furst DE, Mease PJ, Ruderman EM, Horwitz DA, Arkfeld DG, Garrison L, Burge DJ, Blosch CM, Lange ML, McDonnell ND, Weinblatt ME: Etanercept therapy in rheumatoid arthritis. A randomized, controlled trial. Ann Intern Med. 1999, 130: 478-486.

    Article  PubMed  CAS  Google Scholar 

  12. Lipsky PE, van der Heijde DMFM, St Clair EW, Furst DE, Breedveld FC, Kalden JR, Smolen JS, Weisman M, Emery P, Feldmann M, Harriman GR, Maini RN: Infliximab and methotrexate in the treatment of rheumatoid arthritis. N Engl J Med. 2000, 343: 1594-602. 10.1056/NEJM200011303432202.

    Article  PubMed  CAS  Google Scholar 

  13. Sands B, Bank S, Sninsky C, Robinson M, Katz S, Singleton J, Miner P, Safdi M, Galandiuk S, Hanauer S, Varilek G, Buchman A, Rogers V, Salzberg B, Cai B, Rogge H, Schwertschlag U: Safety and activity evaluation of rh-IL-11 in subjects with active Crohn's disease. Gastroenterology. 1999, 117: 59-64.

    Google Scholar 

  14. Sands B, Winston B, Salzberg B, Barish C, Safdi M, Wruble L, Varilek G, Singleton J, Katz S, Miner P, Shapiro M, Schwertschlag US: A randomized, double-masked, placebo-controlled study of rh-IL-11 in Crohn's disease subjects not receiving prednisone. American Gastrologists Association, Orlando,. 1999

    Google Scholar 

  15. Hochberg MC, Chang RW, Dwosh I, Lindsey S, Pincus T, Wolfe F: The American College of Rheumatology 1991 Revised Criteria for the Classification of Global Functional Status in Rheumatoid Arthritis. ArthritisRheum. 1992, 35: 498-502.

    Article  CAS  Google Scholar 

  16. Felson DT, Anderson JJ, Boers M, Bombardier C, Furst D, Goldsmith C, Katz LM, Lightfoot R, Paulus H, Strand V: American College of Rheumatology. Preliminary definition of improvement in rheumatoid arthritis. Arthritis Rheum. 1995, 38: 727-735.

    Article  PubMed  CAS  Google Scholar 

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Acknowledgements

The secretarial assistance of Bettie Stone in preparing the manuscript and the expertise of the clinical coordinators involved with this study are greatly appreciated.

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Authors and Affiliations

  1. Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA

    Larry Moreland

  2. ClinTrials Research Inc., Cary, NC, USA

    Ron Gugliotti

  3. Genetics Institute, Inc., Cambridge, MA, USA

    Kevin King, David Lyons & Ullrich Schwertschlag

  4. 1301 W 38th Street, Suite 609, Austin, TX, USA

    Walter Chase

  5. University of California, San Diego, La Jolla, CA, USA

    Michael Weisman

  6. 133 Scovill Street, Suite 306, Waterbury, CT, 06706, USA

    Thomas Greco

  7. Office of the Dean, Indiana University School of Medicine, Indianapolis, IN, USA

    Rose Fife

  8. Arthritis Center, Boston University School of Medicine, Boston, MA, USA

    Joseph Korn & Robert Simms

  9. Phoenix Center for Clinical Research, Arizona Rheumatology Center, Phoenix, AZ, USA

    John Tesser

  10. Virginia Mason Research Center, Seattle, WA, USA

    Jan Hillson

  11. Florida Arthritis & Allergy Institute PA, Daytona Beach, FL, USA

    Jacques Caldwell

  12. Northwestern University, Office of Clinical Research, Chicago, IL, USA

    Thomas Schnitzer

Authors
  1. Larry Moreland
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  2. Ron Gugliotti
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  3. Kevin King
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  4. Walter Chase
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  5. Michael Weisman
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  7. Rose Fife
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  8. Joseph Korn
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  11. Jan Hillson
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  12. Jacques Caldwell
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  13. Thomas Schnitzer
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  14. David Lyons
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  15. Ullrich Schwertschlag
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Correspondence to Larry Moreland.

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Moreland, L., Gugliotti, R., King, K. et al. Results of a phase-I/II randomized, masked, placebo-controlled trial of recombinant human interleukin-11 (rhIL-11) in the treatment of subjects with active rheumatoid arthritis. Arthritis Res Ther 3, 247 (2001). https://doi.org/10.1186/ar309

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  • DOI: https://doi.org/10.1186/ar309

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