Skip to main content
SpringerLink
Log in

Clinical Efficacy and Tolerability Evaluation of Pentoxifylline in Rheumatoid Arthritis

A Double-Blind, Randomised, Placebo-Controlled Study

  • Original Research Article
  • Published:
Clinical Drug Investigation Aims and scope Submit manuscript

Abstract

Objectives

Recent data suggest that cytokines and tumour necrosis factor (TNF) α play a crucial role in the pathophysiology of chronic synovitis in rheumatoid arthritis (RA). Pentoxifylline has been shown to inhibit TNFα and protect against arthritis. The purpose of the present study was to evaluate the clinical efficacy and tolerability of pentoxifylline in patients with RA.

Patients and methods

Patients of either gender diagnosed as having RA based on American Rheumatism Association criteria who were symptomatic over the last 6 weeks and not receiving any disease-modifying antirheumatic drugs were included. Patients received either pentoxifylline 400mg tablets three times daily or placebo for 24 weeks. They were evaluated by a 28-joint count before treatment and every 2 weeks after treatment for the first month and then at monthly intervals. At every visit, painful and tender joint count and score, pain intensity on a fourpoint scale and on a 100mm visual analogue scale (VAS), swollen joint count and score, and duration of morning stiffness were recorded.

Results

A total of 53 patients (28 receiving pentoxifylline and 25 placebo) were enrolled in the study. Significant improvement in clinical and laboratory variables was noted with pentoxifylline compared with placebo. Both tender and swollen joint count reduced significantly from 16.8 ± 2.6 to 12.7 ± 3.4 and 9.5 ± 4.4, and from 6.5 ± 1.1 to 4.3 ± 1.3 and 3.7±1.6 after 12 and 24 weeks, respectively, with pentoxifylline. Placebo did not decrease the above parameters. Pain intensity measured on the VAS reduced from 66.3 ± 5.7 to 51.9 ± 9.8mm with pentoxifylline after 24 weeks; however, there was an apparent increase in pain intensity with placebo. A statistically significant decrease in erythrocyte sedimentation rate, rheumatoid factor immunoglobulin M, C-reactive protein and malondialdehyde was observed with pentoxifylline compared with placebo. The response rate was 57% with pentoxifylline compared with 19% with placebo.

Conclusion

Pentoxifylline demonstrated significant antirheumatic activity in patients with RA. It significantly improved signs and symptoms of inflammation and disease activity. Pentoxifylline treatment reduced pain, swelling and joint tenderness.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Table I
Table II
Fig. 1
Table III
Fig. 2
Table IV
Table V

Similar content being viewed by others

References

  1. Brennan FM, Field M, Chu CQ, et al. Cytokine expression in rheumatoid arthritis. Br J Rheumatol 1991; Suppl. 30: 76–80

    Google Scholar 

  2. Pober JS, Gimbrone MA Jr, Lapierrer LA, et al. Overlapping patterns of activation of human endothelial cells by interleukin-1, tumor necrosis factor and immune interferon. J Immunol 1986; 13: 1893–6

    Google Scholar 

  3. Scheurich P, Thoma B, Uger U, et al. Immunoregulatory activity of recombinant human tumor necrosis factor (TNF) alpha: induction of TNF receptors on human T cells and TNF alpha mediated enhancement of T cell response. J Immunol 1991; 138: 1786–90

    Google Scholar 

  4. Patarroyo M, Lindborm L, Lundberg C. Leukocyte addhesion: molecular basis and relevance in inflammation. In: Wong PY K, Serhan CN, editors. Cell-cell interactions in the release of Inflammatory Mediators. New York: Plenum Press, 1991: 1–17

    Chapter  Google Scholar 

  5. Dayer JM, Fenner H. The role of cytokines and their inhibitors in arthritis. Ballieres Clin Rheumatol 1992; 6: 485–516

    Article  CAS  Google Scholar 

  6. Chu CQ, Field M, Feldman M, et al. Localization of tumor necrosis factor-alpha in synovial tissue and cartilage pannus junction in patients with rheumatoid arthritis. Arthritis Rheum 1991; 34: 1125–32

    Article  PubMed  CAS  Google Scholar 

  7. Deleuran BW, Chu CQ, Field M, et al. Localization of tumor necrosis factor receptors in the synovial tissue and cartilage pannus junction in patients with rheumatoid arthritis. Implications for local actions of tumor necrosis factor alpha. Arthritis Rheum 1992; 35: 1170–8

    Article  PubMed  CAS  Google Scholar 

  8. Gosset P, Perez T, Lasalle P, et al. Increased TNF alpha secretion by alveolar macrophages from patients with rheumatoid arthitis. Am Rev Respir Dis 1991; 143: 593–7

    PubMed  CAS  Google Scholar 

  9. Ancochea J, Alvaro-Gracia JM, Laffon A, et al. TNF alpha and IL-6 production by alveolar macrophages in rheumatoid arthritis patients with interstitial lung disease [abstract]. Arthritis Rheum 1993; Suppl. 36: A161

  10. Elliot MM, Maini RN, Feldmann M, et al. Treatment of rheumatoid arthritis with chimeric monoclonal antibodies to tumor necrosis factor alpha. Arthritis Rheum 1993; 36: 1681–90

    Article  Google Scholar 

  11. Juan-Manuel A, Espinoza LR. Phospodiesterase inhibitor pentoxifylline. An antiinflammatory/immunomodulatory drug potentially useful in some rheumatic diseases. J Rheumatol 1995; 22: 595–9

    Google Scholar 

  12. Han J, Thompson P, Beutler B. Dexamethasone and pentoxifylline inhibit endotoxin-induced cachectin/tumor necrosis factor synthesis at separate points in the signaling pathway. J Exp Med 1990; 172: 391–4

    Article  PubMed  CAS  Google Scholar 

  13. Robert PJ, Yong KL, Khwaja A, et al. Pentoxifylline at clinically achievable level inhibits FMLP-induced neutrophil responses, but not priming, upregulation of cell-adhesion molecules or migration induced by GM-CSF. Eur J Haematol 1993; 50: 1–10

    Article  Google Scholar 

  14. Peterson TC. Pentoxifylline prevents fibrosis in an animal model and inhibits platelet derived growth factor-driven proliferation of fibroblasts. Hepatology 1993; 17: 486–93

    PubMed  CAS  Google Scholar 

  15. Zabel P, Wolter DT, Schonharting MM, et al. Oxypentifylline in endotoxaemia. Lancet 1989; 30: 1474–7

    Article  Google Scholar 

  16. Carrier M, Perrault LP, Tronc F, et al. Pentoxifylline decreases cyclosporin-induced renal endothelin release and vasoconstriction. Ann Thorac Surg 1993; 55: 490–2

    Article  PubMed  CAS  Google Scholar 

  17. Kiely PD, Gillespie KM, Oliveira DB. Oxypentfylline inhibits tumor necrosis factor alpha mRNA transcription and protects against arthritis in mercuric chloride treated brown Norway rats. Eur J Immunol 1995; 25(10): 2899–906

    Article  PubMed  CAS  Google Scholar 

  18. Maksymowych WP, Avina-Zubieta A, Luong MH, et al. An open study of pentoxifylline in the treatment of severe refractory rheumatoid arthritis. J Rheumatol 1995; 22: 625–9

    PubMed  CAS  Google Scholar 

  19. Huizinga TW, Dijkmans BA, van-der-Velde-EA, et al. An open study of pentoxifylline and thalidomide as adjuvant therapy in the treatment of rheumatoid arthritis. Ann Rheum Dis 1996; 55(11): 833–6

    Article  PubMed  CAS  Google Scholar 

  20. Arnett FC, Edworthy SM, Bloch DA, et al. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum 1988; 31: 315–24

    Article  PubMed  CAS  Google Scholar 

  21. MacDonald MJ, Shahidi NT, Allen DB, et al. Pentoxifylline in the treatment of children with new-onset type-I diabetes mellitus. JAMA 1994; 271: 27–8

    Article  PubMed  CAS  Google Scholar 

  22. Kiely PDW, Gillespie KM, Oliveira DBG. Oxpentifylline enhances the Th2 lymphokine environment and protects against arthritis in mercuric chloride induced autoimmunity [abstract]. Immunology 1994; (Suppl 1) 9: S339

  23. Anaya JM, Gutierrez M, Silveira LH, et al. Effect of pentoxifylline on TNF alpha and IL-10 production in stimulated mononuclear cells from rheumatoid arthritis [abstract]. Arthritis Rheum 1994; (Suppl 1) 83: 27

  24. Elliot MJ, Maini RN, Feldmann M, et al. Treatment of rheumatoid arthritis with chimeric monoclonal antibodies to tumor necrosis factor alpha. Arthritis Rheum 1993; 36: 1681–90

    Article  Google Scholar 

  25. Elliot MJ, Maini RN, Feldmann M, et al. Randomised doubleblind comparison of chimeric monoclonal antibody to tumor necrosis factor alpha (cA2) versus placebo in rheumatoid arthritis. Lancet 1994; 344: 1105–10

    Article  Google Scholar 

  26. Rankin ECC, Choy EHS, Kassimos D, et al. A double-blind placebo controlled, ascending dose trial of the recombinant humanised anti-TNF alpha antibody CDP 571 in patients with rheumatoid arthritis. A preliminary report. Arthritis Rheum 1994; 37: S2905

    Google Scholar 

  27. Mandell GL, Sullivan GW. Pentoxifylline: an inhibitor of inflammatory cytokine activity. In: Mandell GL, Novick WJ, editors. Pentoxifylline, leukocytes and Cytokines. Proceedings of a Symposium; 1991 Mar 1–6; Scottsdale, Arizona

  28. Strieter RM, Remick PA, Ward RN, et al. Cellular and molecular regulation of tumour necrosis factor al-ha production by pentoxifylline. Biochem Biophys Commun Res 1988; 155: 1230–6

    Article  CAS  Google Scholar 

  29. Bienvenu J, Doche C, Gutowski MC, et al. The production of proinflammatory cytokines and cytokines involved in the TH1/TH2 balance is modulated by pentoxifylline. Abstracts from International Congress — From cyclic AMP to cytokines. Pentoxifylline: present and Future, Budapest, July 1994

  30. Hussey DH, Friedland JL. Second report of a pilot study of pentoxifylline in the treatment of late-radiation necrosis. In: Mandell GL, Novick WJ, editors. Pentoxifylline, Leukocyte and Cytokines. Proceedings of a symposium; 1991 Mar 24–33; Scottdale, Arizona

  31. Antin JH, Ferrara JLM. Cytokine dysregulation and acute graftversus host disease. Blood 1992; 80: 2964–8

    PubMed  CAS  Google Scholar 

  32. Otterness IG. The value of C-reactive protein measurement in rheumatoid arthritis. Semin Arthritis Rheum 1994; 24: 91–104

    Article  PubMed  CAS  Google Scholar 

  33. Cash JM, Klippel JH. Second-line drug therapy for rheumatoid arthritis. N Engl J Med 1994; 330: 1369–75

    Google Scholar 

  34. Feldson DT, Anderson JJ, Meenam RF. Use of short-term efficacy/toxicity tradeoffs to select second-line drugs in rheumatoid arthritis: a meta-analysis of published clinical trials. Arthritis Rheum 1992; 35: 1117–25

    Article  Google Scholar 

Download references

Acknowledgements

The authors gratefully acknowledge Hoechst-Marion Roussel, Mumbai, India for the supply of the research material to conduct the study.

Author information

Authors and Affiliations

  1. Department of Clinical Pharmacology and Therapeutics, Nizam’s Institute of Medical Sciences, Panjagutta, Hyderabad, 500 082, India

    P. R. Usha, M. U. R. Naidu & Renuka Datla

Authors
  1. P. R. Usha
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. M. U. R. Naidu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Renuka Datla
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to P. R. Usha.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Usha, P.R., Naidu, M.U.R. & Datla, R. Clinical Efficacy and Tolerability Evaluation of Pentoxifylline in Rheumatoid Arthritis. Clin. Drug Investig. 22, 329–339 (2002). https://doi.org/10.2165/00044011-200222050-00007

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00044011-200222050-00007

Keywords

Search

Navigation