Double blind controlled phase III multicenter clinical trial with interferon gamma in rheumatoid arthritis

Hofschneider, P. H.; Winter, U. J.; Lemmel, E.-M.; Brölz, B.; Gaus, Wilhelm; Schmid, S.; Obert, Hans-Joachim; Stetter, Christian; Auer, I. O.; Papst, Cheraz Cherif; Boesken, W. H.; Stierle, H. E.; Botzenhardt, U.; Reemtsen, W.; Brackertz, D.; Richter, Daniel; Diehl, Volker; Kalle, A.; Gärtner, Ch.; Herzig, Shoshana J.; Goronzy, Jörg J.; Weyand, C. M.; Kalden, Joachim R.; Strobel, Fred; Machalke, K.; Peter, Hans; Meske, S; Schattenkirchner, M; Krüger, Klaus; Sprekeler, R.; Waller, H. D.; Saal, J. G.; Warnatz, H; Lemm, G.; Wilms, K.; Stolzenburg, T.

doi:10.1007/bf00302149

Cited by 33 publications

(8 citation statements)

References 32 publications

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“…Among the double blind controlled trials, while couple trials have shown statistically significant clinical efficacy of IFN-γ in the treatment of RA [98, 99], other trials showed a trend towards improvement but failed to show a statistically significant therapeutic result [100, 101]. A few earlier uncontrolled trials showed a beneficial effect of IFN-γ in a proportion of RA patients [102–104].…”

Section: Ifn-γ-induced Immune Regulationmentioning

confidence: 99%

Immunomodulation of autoimmune arthritis by pro-inflammatory cytokines

2017

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Pro-inflammatory cytokines promote autoimmune inflammation and tissue damage, while anti-inflammatory cytokines help resolve inflammation and facilitate tissue repair. Over the past few decades, this general feature of cytokine-mediated events has offered a broad framework to comprehend the pathogenesis of autoimmune and other immune-mediated diseases, and to successfully develop therapeutic approaches for diseases such as rheumatoid arthritis (RA). Anti-tumor necrosis factor-α (TNF-α) therapy is a testimony in support of this endeavor. However, many patients with RA fail to respond to this or other biologics, and some patients may suffer unexpected aggravation of arthritic inflammation or other autoimmune effects. These observations combined with rapid advancements in immunology in regard to newer cytokines and T cell subsets have enforced a re-evaluation of the perceived pathogenic attribute of the pro-inflammatory cytokines. Studies conducted by others and us in experimental models of arthritis involving direct administration of IFN-γ or TNF-α; in vivo neutralization of the cytokine; the use of animals deficient in the cytokine or its receptor; and the impact of the cytokine or anti-cytokine therapy on defined T cell subsets have revealed a paradoxical anti-inflammatory and immunoregulatory attributes of these two cytokines. Similar studies in other models of autoimmunity as well as limited studies in arthritis patients have also unveiled the disease-protective effects of these pro-inflammatory cytokines. A major mechanism in this regard is the altered balance between the pathogenic T helper 17 (Th17) and protective T regulatory (Treg) cells in favor of the latter. However, it is essential to consider that this aspect of the pro-inflammatory cytokines is context-dependent such that the dose and timing of intervention, the experimental model of the disease under study, and the differences in individual responsiveness can influence the final outcomes. Nevertheless, the realization that pro-inflammatory cytokines can also be immunoregulatory offers a new perspective in fully understanding the pathogenesis of autoimmune diseases and in designing better therapies for controlling them.

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Section: Ifn-γ-induced Immune Regulationmentioning

confidence: 99%

Immunomodulation of autoimmune arthritis by pro-inflammatory cytokines

2017

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“…Bei einer durchschnittlichen Dauer einiger klinischer Verbesserungen von 2 Monaten, die allerdings bei der kleinen Patientenzahl das Signifikanzniveau nicht überschritten, und einer guten Veträglichkeit erscheint eine Fortführung der IL-6-mAk-Studie unter doppelblinden, plazebo-kontrollierten Bedingungen nach Humanisierung oder Chimärisierung des Antikörpers, selbst unter Berück-sichtgung des erheblichen Plazeboeffektes gerade bei diesem Patientenkollektiv, gerechtfertigt Zytokine in der Therapie der RA Therapeutische Interventionen bei der RA mit IFN-γ stellen die ersten Versuche dar, bei dieser Entität in das Zytokinnetzwerk einzugreifen. Die Studienlage ist dabei uneinheitlich; vier Studien zeigten einen im Vergleich zu Plazebo signifikanten therapeutischen Nutzen, zwei andere Arbeiten konnten, bei allerdings kleineren Fallzahlen, keinen Unterschied zu Plazebo finden (Übersicht in (2,10)). Selbst angesichts der Uneinheitlichkeit dieser Aussagen lässt sich sicherlich unzweifelhaft feststellen, dass Ausmaß und Dauer des Therapieerfolges von IFN-γ bei der RA nicht mit der anti-TNF-α-Behandlung zu vergleichen ist.…”

Section: Il-6-inhibitorenunclassified

Neue immuntherapeutische Strategien bei Autoimmunerkrankungen

Lorenz

Geiler²

2001

Dtsch med Wochenschr

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“…Dies macht auch eine weitere, von der Deutschen Lymphokinstudiengruppe initiierte IFN-γ Studie bei RA deutlich: über 12 Wochen erhielten 249 RA Patienten IFN-γ oder Placebo [28]. Dies macht auch eine weitere, von der Deutschen Lymphokinstudiengruppe initiierte IFN-γ Studie bei RA deutlich: über 12 Wochen erhielten 249 RA Patienten IFN-γ oder Placebo [28].…”

Section: Hemmung Von Il-6unclassified