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Is There A Role For Tnf-α Antagonists In The Treatment Of Ssc? Eustar Expert Consensus Development Using The Delphi Technique
Authors
Airo P.
Alegre-Sancho J.J.
+34 more
Allanore Y.
Balbir Gurman A.
Caporali R.
Caramaschi P.
Carreira P.E.
Chizzolini C.
Cutolo M.
De Keyser F.
Distler J.H.W.
Distler O.
Farge-Bancel D.
Garcia De La Pena Lefebvre P.
Hesselstrand R.
Iannone F.
Jordan S.
Kucharz E.J.
Launay D.
Lukacova O.
Marasini B.
Marques Neto J.F.
Martinovic D.
Matucci-Cerinic M.
Muller-Ladner U.
Radic M.
Rednic S.
Riemekasten G.
Rovensky J.
Seidel M.F.
Senel S.
Smith V.
Sunderkotter C.
Ton E.
Tuncay Duruoz M.
Van Laar J.M.
Publication date
26 November 2015
Publisher
Abstract
Objective: To obtain experiences and expert opinion on treatment of SSc patients with TNF-α antagonists. Methods: An investigation was carried out among the EUSTAR centres into their expertise on use of TNF-α antagonists. Assessment forms on the frequency of TNF-α inhibitor use were distributed to EULAR Scleroderma Trials and Research Group (EUSTAR) centres. Afterwards, a three round Delphi exercise was performed to obtain expert consensus on the use of TNF-α inhibitors in SSc. Results: Seventy-nine centres returned information on use of TNF-α antagonists in SSc patients. A total of 65 patients were treated with TNF-a inhibitors in 14 different centres. Forty-eight of the 65 patients treated with TNF-α inhibitors improved. Improvement was mainly seen in patients with arthritis, whereas the effects on fibrosis varied. In the first round of the subsequent Delphi approach, 71 out of 79 experts stated that they would use TNF-α antagonists in SSc. Arthritis was suggested as an indication for TNFa antagonists by 75% of the experts. However, after the third stage of the Delphi exercise, the acceptance for the off-label use of TNF-a antagonists decreased and 59% recommended that TNF-α antagonists should not be used or only used in clinical trials in SSc patients, while 38% of the experts suggested the use of TNF-a antagonists for arthritis associated with SSc. Conclusions: Most of the experts do not recommend the routine use of TNF-a antagonists in systemic sclerosis. Arthritis might be a potential indication in SSc, although controlled clinical trials with TNF-α antagonists are needed before general recommendations can be given. © Copyright Clinical and Experimental Rheumatology 2011.292 SUPPL. 65S40S45Keyser, F.D., Mielants, H., Veys, E.M., Current use of biologicals for the treatment of spondyloarthropathies (2001) Expert Opin Pharmacother, 2, pp. 85-93Olsen, N.J., Stein, C.M., New drugs for rheumatoid arthritis (2004) N Engl J Med, 350, pp. 2167-2179Chua, C.C., Chua, B.H., Tumor necrosis factor-alpha induces mRNA for collagenase and TIMP in human skin fibroblasts (1990) Connect Tissue Res, 25, pp. 161-170Mauviel, A., Daireaux, M., Redini, F., Galera, P., Loyau, G., Pujol, J.P., Tumor necrosis factor inhibits collagen and fibronectin synthesis in human dermal fibroblasts (1988) FEBS Lett, 236, pp. 47-52Liu, J.Y., Brass, D.M., Hoyle, G.W., Brody, A.R., TNF-alpha receptor knockout mice are protected from the fibroproliferative effects of inhaled asbestos fibers (1998) Am J Pathol, 153, pp. 1839-1847Piguet, P.F., Vesin, C., Treatment by human recombinant soluble TNF receptor of pulmonary fibrosis induced by bleomycin or silica in mice (1994) Eur Respir J, 7, pp. 515-518Khan, S.B., Cook, H.T., Bhangal, G., Smith, J., Tam, F.W., Pusey, C.D., Antibody blockade of TNF-alpha reduces inflammation and scarring in experimental crescentic glomerulonephritis (2005) Kidney Int, 67, pp. 1812-1820Distler, J.H., Schett, G., Gay, S., Distler, O., The controversial role of tumor necrosis factor alpha in fibrotic diseases (2008) Arthritis Rheum, 58, pp. 2228-2235Varga, J., Abraham, D., Systemic sclerosis: A prototypic multisystem fibrotic disorder (2007) J Clin Invest, 117, pp. 557-567Gabrielli, A., Avvedimento, E.V., Krieg, T., Scleroderma (2009) N Engl J Med, 360, pp. 1989-2003Bosello, S., De Santis, M., Tolusso, B., Zoli, A., Ferraccioli, G., Tumor necrosis factor-alpha inhibitor therapy in erosive polyarthritis secondary to systemic sclerosis (2005) Ann Intern Med, 143, pp. 918-920Antoniou, K.M., Mamoulaki, M., Malagari, K., Infliximab therapy in pulmonary fibrosis associated with collagen vascular disease (2007) Clin Exp Rheumatol, 25, pp. 23-28Bargagli, E., Galeazzi, M., Bellisai, F., Volterrani, L., Rottoli, P., Infliximab treatment in a patient with systemic sclerosis associated with lung fibrosis and pulmonary hypertension (2008) Respiration, 75, pp. 346-349Denton, C.P., Engelhart, M., Tvede, N., An open-label pilot study of infliximab therapy in diffuse cutaneous systemic sclerosis (2009) Ann Rheum Dis, 68, pp. 1433-1439Ellman, M.H., Macdonald, P.A., Katz, R.S., Open label use of etanercept in eight scleroderma patients (2003) Ann Rheum Dis, 62 (SUPPL. 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It is time to cut the Gordian knot and develop a prevention or rescue strategy (2009) Ann Rheum Dis, 68, pp. 1377-138
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