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Letter to the Editor
Editor, – Professor McColl is to be congratulated for his admirable review of TNF-targeted antibodies (Aust Prescr 2004;27:43-6). These protein therapies may still need to be used as synergists with well-tried drugs such as methotrexate. They are very expensive and a real burden to both the Pharmaceutical Benefits Scheme (PBS) and to rheumatologists, who must provide much supportive data justifying the patient's need. Some of the criteria for their use may be suspect.1
Two of these antibodies can bind cell-bound TNF, perhaps inducing apoptosis of the TNF-producing cells. In the long term, this may compromise natural defences against comorbidities, for example tumours, tuberculosis. (The third drug (etanercept) binds TNF after release from the cells.)
There are much cheaper drugs for controlling TNF production such as thalidomide and oxpentifylline (pentoxifylline).2 Thalidomide may be in the 'too-hard basket', but oxpentifylline has been used for more than 30 years to treat poor circulation.3 Oxpentifylline is a proven alternative to steroids for controlling granulomatous inflammation in Hansen's disease.45 So its safety is not an issue. Its short half-life3 permits rapid suspension of use should compromising situations such as infections arise. For optimal efficacy in treating chronic inflammation oxpentifylline may have to be used synergistically.6 One month's supply (400 mg tds) costs approximately $80 in Australia.
You will not read much about company-sponsored trials as the drug is out of patent and regulatory agencies do not favour drug combinations. The big question is whether support can be found for clinical trials of non-protein TNF-blockers. Positive outcomes might be much reduced costs to the PBS and widening the availability of TNF inhibition therapy.
Therapeutics Research Unit
Department of Medicine
Princess Alexandra Hospital
- Lu CY, Day RO, Williams KM. Lack of evidence for an association between rheumatoid factor status and clinical response in patients with rheumatoid arthritis treated with TNF alpha inhibitors. Intern Med J 2004;34:S104.
- Strieter RM, Remick DG, Ward PA, Spengler RN, Lynch JP, Larrick J, et al. Cellular and molecular regulation of tumor necrosis factor-alpha production by pentoxifylline. Biochem Biophys Res Commun 1988;155:1230-6.
- Ward A, Clissold SP. Pentoxifylline. A review of its pharmacodynamic and pharmacokinetic properties, and its therapeutic efficacy. Drugs 1987;34:50-97.
- Nery JA, Perisse AR, Sales AM, Vieira LM, Souza RV, Sampaio EP, et al. The use of pentoxifylline in the treatment of type 2 reactional episodes in leprosy. Indian J Lepr 2000;72:457-67.
- Sampaio EP, Moraes MO, Nery JA, Santos AR, Matos HC, Sarno EN. Pentoxifylline decreases in vivo and in vitro tumor necrosis factor-alpha (TNF-alpha) production in lepromatous leprosy patients with erythema nodosum leprosum (ENL). Clin Exp Immunol 1998;111:300-8.
- Whitehouse MW. (Point of view) Anti-TNF-Î± therapy for chronic inflammation: reconsidering pentoxifylline as an alternative to therapeutic protein drugs. Inflammopharmacology 2004;12:223-7.
- Dubost JJ, Soubrier M, Ristori JM, Beaujon G, Oualid T, Bussiere JL, Sauvezie B. An open study of the anti-TNF alpha agent pentoxifylline in the treatment of rheumatoid arthritis. Rev Rhum Engl Ed 1997;64:789-93.
- Huizinga TW, Dijkmans BA, van der Velde EA, van de Pouw Kraan TC, Verweij CL, Breedveld FC. An open study of pentoxyfylline and thalidomide as adjuvant therapy in the treatment of rheumatoid arthritis. Ann Rheum Dis 1996;55:833-6.
- Scoville CD. Pilot study using the combination of methotrexate and thalidomide in the treatment of rheumatoid arthritis. Clin Exp Rheumatol 2001;19:360-1.
- Gutiérrez-RodrÃguez O, Starusta-Bacal P, Gutiérrez-Montes O. Treatment of refractory rheumatoid arthritis: the thalidomide experience. J Rheumatol 1989;16:158-63.