Isabelle Koné-Paut1, Stéphanie Tellier2, Alexandre Belot3, Karine Brochard2, Corinne Guitton1, Isabelle Marie1, Ulrich Meinzer4, Bilade Cherqaoui5, Caroline Galeotti1, Nadja Boukhedouni6, Helene Agostini6, Moshe Arditi7, Virginie Lambert8, Céline Piedvache6. 1. CeRéMAIA, AP-HP, Bicêtre Hospital, University of Paris Sud Saclay, Paris, France. 2. University of Toulouse, Toulouse, France. 3. University of Lyon, International Center for Research in Infectious Diseases, INSERM U1111, ENS, Lyon, France. 4. Robert Debre University Hospital, Paris, France. 5. CeRéMAIA, Bicêtre Hospital, AP-HP, University of Paris Sud Saclay, INSERM U1173, Paris, France. 6. AP-HP, University of Paris Saclay, Bicêtre Hospital, Paris, France. 7. Cedars-Sinai Medical Center, Los Angeles, California. 8. Institut Mutualiste Montsouris and Bicêtre Hospital, AP-HP, University of Paris Sud Saclay, Paris, France.
Abstract
OBJECTIVE: Anakinra has been shown to be successful in preventing and treating cardiovascular lesions both in experimental murine models of Kawasaki disease (KD) and in several studies on intravenous immunoglobulin (IVIG)- and steroid-resistant patients with KD. This study was undertaken to determine the safety of blocking interleukin-1 in patients with IVIG-resistant KD. METHODS: Sixteen patients were included in the present study. Patients with KD who were not responsive to 1 or more courses of 2 mg/kg of IVIG received anakinra by subcutaneous daily injections. Starting doses were 2 mg/kg of IVIG (4 mg/kg in patients who were age <8 months and who weighed ≥5 kilograms), and the dose was increased up to 6 mg/kg every 24 hours if the patient's body temperature remained >38°C, indicative of a fever. Treatment duration was 14 days. The last visit was on day 45. Primary outcome was abatement of fever. Secondary measures included disease activity, coronary artery Z score, and C-reactive protein (CRP) levels. RESULTS: Seventy-five percent of patients in the intention-to-treat group and 87.5% in the per-protocol group became afebrile within 48 hours of the last escalation dose of anakinra. Reduction of disease activity by 50% was indicated on 93.3% (95% confidence interval [95% CI] 68.1-99.8%) of physician evaluations and on 100% (95% CI 73.5-100%) of parent evaluations. CRP values normalized by day 30. At the initial screening, 12 of 16 patients had a maximum coronary artery Z score of >2, and 10 of 16 patients had a maximum Z score of >2.5. At day 45, 5 of 10 patients (50% [95% CI 18.7-81.3%]) and 6 of 12 patients (50% [95% CI 21.1-78.9%]) had achieved coronary artery Z scores of <2.5 and <2, respectively. Five serious adverse events were observed in 3 patients, but no serious infections or deaths occurred. CONCLUSION: Anakinra was well tolerated in the study patients and may have some efficacy in reducing fever, markers of systemic inflammation, and coronary artery dilatation in individuals with IVIG-refractory KD.
OBJECTIVE: Anakinra has been shown to be successful in preventing and treating cardiovascular lesions both in experimental murine models of Kawasaki disease (KD) and in several studies on intravenous immunoglobulin (IVIG)- and steroid-resistant patients with KD. This study was undertaken to determine the safety of blocking interleukin-1 in patients with IVIG-resistant KD. METHODS: Sixteen patients were included in the present study. Patients with KD who were not responsive to 1 or more courses of 2 mg/kg of IVIG received anakinra by subcutaneous daily injections. Starting doses were 2 mg/kg of IVIG (4 mg/kg in patients who were age <8 months and who weighed ≥5 kilograms), and the dose was increased up to 6 mg/kg every 24 hours if the patient's body temperature remained >38°C, indicative of a fever. Treatment duration was 14 days. The last visit was on day 45. Primary outcome was abatement of fever. Secondary measures included disease activity, coronary artery Z score, and C-reactive protein (CRP) levels. RESULTS: Seventy-five percent of patients in the intention-to-treat group and 87.5% in the per-protocol group became afebrile within 48 hours of the last escalation dose of anakinra. Reduction of disease activity by 50% was indicated on 93.3% (95% confidence interval [95% CI] 68.1-99.8%) of physician evaluations and on 100% (95% CI 73.5-100%) of parent evaluations. CRP values normalized by day 30. At the initial screening, 12 of 16 patients had a maximum coronary artery Z score of >2, and 10 of 16 patients had a maximum Z score of >2.5. At day 45, 5 of 10 patients (50% [95% CI 18.7-81.3%]) and 6 of 12 patients (50% [95% CI 21.1-78.9%]) had achieved coronary artery Z scores of <2.5 and <2, respectively. Five serious adverse events were observed in 3 patients, but no serious infections or deaths occurred. CONCLUSION: Anakinra was well tolerated in the study patients and may have some efficacy in reducing fever, markers of systemic inflammation, and coronary artery dilatation in individuals with IVIG-refractory KD.
Authors: Jochen Pfeifer; Bernhard Thurner; Christoph Kessel; Natalie Fadle; Parastoo Kheiroddin; Evi Regitz; Marie-Christin Hoffmann; Igor Age Kos; Klaus-Dieter Preuss; Yvan Fischer; Klaus Roemer; Stefan Lohse; Kristina Heyne; Marie-Claire Detemple; Michael Fedlmeier; Hendrik Juenger; Harald Sauer; Sascha Meyer; Tilman Rohrer; Helmut Wittkowski; Sören L Becker; Katja Masjosthusmann; Robert Bals; Stephan Gerling; Sigrun Smola; Moritz Bewarder; Einat Birk; Andre Keren; Michael Böhm; André Jakob; Hashim Abdul-Khaliq; Jordi Anton; Michael Kabesch; Rosa Maria Pino-Ramirez; Dirk Foell; Lorenz Thurner Journal: Lancet Rheumatol Date: 2022-03-29
Authors: Stefanie Marek-Iannucci; Asli D Yildirim; Syed M Hamid; Asli B Ozdemir; Angela C Gomez; Begüm Kocatürk; Rebecca A Porritt; Michael C Fishbein; Takao Iwawaki; Magali Noval Rivas; Ebru Erbay; Moshe Arditi Journal: JCI Insight Date: 2022-03-22