Sarilumab for Relapse of Polymyalgia Rheumatica during Glucocorticoid Taper.

Autor:	Spiera RF; From the Hospital for Special Surgery, Weill Cornell Medical College, New York (R.F.S.), and Regeneron Pharmaceuticals, Tarrytown (A.G., M.C.N., B.A., R.B., G.D.Y.) - both in New York; the Vasculitis and Glomerulonephritis Center, Massachusetts General Hospital, Harvard Medical School, Boston (S.U.), and Sanofi, Cambridge (J.S., N.P.) - both in Massachusetts; the Division of Rheumatology, Mayo Clinic College of Medicine, Rochester, MN (K.J.W.); Sanofi, Bridgewater, NJ (W.W., Y.L.); the Department of Rheumatology and Clinical Immunology, Charité University Medicine, Berlin (F.B.); CHRU de Brest, Service de Rhumatologie, Brest (V.D.-P.), and Sanofi, Chilly-Mazarin (F.M.) - both in France; the Division of Rheumatology and Immunology, Cantonal Hospital St. Gallen, St. Gallen, Switzerland (A.R.-R.); and Anglia Ruskin University, Cambridge, United Kingdom (B.D.)., Unizony S; From the Hospital for Special Surgery, Weill Cornell Medical College, New York (R.F.S.), and Regeneron Pharmaceuticals, Tarrytown (A.G., M.C.N., B.A., R.B., G.D.Y.) - both in New York; the Vasculitis and Glomerulonephritis Center, Massachusetts General Hospital, Harvard Medical School, Boston (S.U.), and Sanofi, Cambridge (J.S., N.P.) - both in Massachusetts; the Division of Rheumatology, Mayo Clinic College of Medicine, Rochester, MN (K.J.W.); Sanofi, Bridgewater, NJ (W.W., Y.L.); the Department of Rheumatology and Clinical Immunology, Charité University Medicine, Berlin (F.B.); CHRU de Brest, Service de Rhumatologie, Brest (V.D.-P.), and Sanofi, Chilly-Mazarin (F.M.) - both in France; the Division of Rheumatology and Immunology, Cantonal Hospital St. Gallen, St. Gallen, Switzerland (A.R.-R.); and Anglia Ruskin University, Cambridge, United Kingdom (B.D.)., Warrington KJ; From the Hospital for Special Surgery, Weill Cornell Medical College, New York (R.F.S.), and Regeneron Pharmaceuticals, Tarrytown (A.G., M.C.N., B.A., R.B., G.D.Y.) - both in New York; the Vasculitis and Glomerulonephritis Center, Massachusetts General Hospital, Harvard Medical School, Boston (S.U.), and Sanofi, Cambridge (J.S., N.P.) - both in Massachusetts; the Division of Rheumatology, Mayo Clinic College of Medicine, Rochester, MN (K.J.W.); Sanofi, Bridgewater, NJ (W.W., Y.L.); the Department of Rheumatology and Clinical Immunology, Charité University Medicine, Berlin (F.B.); CHRU de Brest, Service de Rhumatologie, Brest (V.D.-P.), and Sanofi, Chilly-Mazarin (F.M.) - both in France; the Division of Rheumatology and Immunology, Cantonal Hospital St. Gallen, St. Gallen, Switzerland (A.R.-R.); and Anglia Ruskin University, Cambridge, United Kingdom (B.D.)., Sloane J; From the Hospital for Special Surgery, Weill Cornell Medical College, New York (R.F.S.), and Regeneron Pharmaceuticals, Tarrytown (A.G., M.C.N., B.A., R.B., G.D.Y.) - both in New York; the Vasculitis and Glomerulonephritis Center, Massachusetts General Hospital, Harvard Medical School, Boston (S.U.), and Sanofi, Cambridge (J.S., N.P.) - both in Massachusetts; the Division of Rheumatology, Mayo Clinic College of Medicine, Rochester, MN (K.J.W.); Sanofi, Bridgewater, NJ (W.W., Y.L.); the Department of Rheumatology and Clinical Immunology, Charité University Medicine, Berlin (F.B.); CHRU de Brest, Service de Rhumatologie, Brest (V.D.-P.), and Sanofi, Chilly-Mazarin (F.M.) - both in France; the Division of Rheumatology and Immunology, Cantonal Hospital St. Gallen, St. Gallen, Switzerland (A.R.-R.); and Anglia Ruskin University, Cambridge, United Kingdom (B.D.)., Giannelou A; From the Hospital for Special Surgery, Weill Cornell Medical College, New York (R.F.S.), and Regeneron Pharmaceuticals, Tarrytown (A.G., M.C.N., B.A., R.B., G.D.Y.) - both in New York; the Vasculitis and Glomerulonephritis Center, Massachusetts General Hospital, Harvard Medical School, Boston (S.U.), and Sanofi, Cambridge (J.S., N.P.) - both in Massachusetts; the Division of Rheumatology, Mayo Clinic College of Medicine, Rochester, MN (K.J.W.); Sanofi, Bridgewater, NJ (W.W., Y.L.); the Department of Rheumatology and Clinical Immunology, Charité University Medicine, Berlin (F.B.); CHRU de Brest, Service de Rhumatologie, Brest (V.D.-P.), and Sanofi, Chilly-Mazarin (F.M.) - both in France; the Division of Rheumatology and Immunology, Cantonal Hospital St. Gallen, St. Gallen, Switzerland (A.R.-R.); and Anglia Ruskin University, Cambridge, United Kingdom (B.D.)., Nivens MC; From the Hospital for Special Surgery, Weill Cornell Medical College, New York (R.F.S.), and Regeneron Pharmaceuticals, Tarrytown (A.G., M.C.N., B.A., R.B., G.D.Y.) - both in New York; the Vasculitis and Glomerulonephritis Center, Massachusetts General Hospital, Harvard Medical School, Boston (S.U.), and Sanofi, Cambridge (J.S., N.P.) - both in Massachusetts; the Division of Rheumatology, Mayo Clinic College of Medicine, Rochester, MN (K.J.W.); Sanofi, Bridgewater, NJ (W.W., Y.L.); the Department of Rheumatology and Clinical Immunology, Charité University Medicine, Berlin (F.B.); CHRU de Brest, Service de Rhumatologie, Brest (V.D.-P.), and Sanofi, Chilly-Mazarin (F.M.) - both in France; the Division of Rheumatology and Immunology, Cantonal Hospital St. Gallen, St. Gallen, Switzerland (A.R.-R.); and Anglia Ruskin University, Cambridge, United Kingdom (B.D.)., Akinlade B; From the Hospital for Special Surgery, Weill Cornell Medical College, New York (R.F.S.), and Regeneron Pharmaceuticals, Tarrytown (A.G., M.C.N., B.A., R.B., G.D.Y.) - both in New York; the Vasculitis and Glomerulonephritis Center, Massachusetts General Hospital, Harvard Medical School, Boston (S.U.), and Sanofi, Cambridge (J.S., N.P.) - both in Massachusetts; the Division of Rheumatology, Mayo Clinic College of Medicine, Rochester, MN (K.J.W.); Sanofi, Bridgewater, NJ (W.W., Y.L.); the Department of Rheumatology and Clinical Immunology, Charité University Medicine, Berlin (F.B.); CHRU de Brest, Service de Rhumatologie, Brest (V.D.-P.), and Sanofi, Chilly-Mazarin (F.M.) - both in France; the Division of Rheumatology and Immunology, Cantonal Hospital St. Gallen, St. Gallen, Switzerland (A.R.-R.); and Anglia Ruskin University, Cambridge, United Kingdom (B.D.)., Wong W; From the Hospital for Special Surgery, Weill Cornell Medical College, New York (R.F.S.), and Regeneron Pharmaceuticals, Tarrytown (A.G., M.C.N., B.A., R.B., G.D.Y.) - both in New York; the Vasculitis and Glomerulonephritis Center, Massachusetts General Hospital, Harvard Medical School, Boston (S.U.), and Sanofi, Cambridge (J.S., N.P.) - both in Massachusetts; the Division of Rheumatology, Mayo Clinic College of Medicine, Rochester, MN (K.J.W.); Sanofi, Bridgewater, NJ (W.W., Y.L.); the Department of Rheumatology and Clinical Immunology, Charité University Medicine, Berlin (F.B.); CHRU de Brest, Service de Rhumatologie, Brest (V.D.-P.), and Sanofi, Chilly-Mazarin (F.M.) - both in France; the Division of Rheumatology and Immunology, Cantonal Hospital St. Gallen, St. Gallen, Switzerland (A.R.-R.); and Anglia Ruskin University, Cambridge, United Kingdom (B.D.)., Bhore R; From the Hospital for Special Surgery, Weill Cornell Medical College, New York (R.F.S.), and Regeneron Pharmaceuticals, Tarrytown (A.G., M.C.N., B.A., R.B., G.D.Y.) - both in New York; the Vasculitis and Glomerulonephritis Center, Massachusetts General Hospital, Harvard Medical School, Boston (S.U.), and Sanofi, Cambridge (J.S., N.P.) - both in Massachusetts; the Division of Rheumatology, Mayo Clinic College of Medicine, Rochester, MN (K.J.W.); Sanofi, Bridgewater, NJ (W.W., Y.L.); the Department of Rheumatology and Clinical Immunology, Charité University Medicine, Berlin (F.B.); CHRU de Brest, Service de Rhumatologie, Brest (V.D.-P.), and Sanofi, Chilly-Mazarin (F.M.) - both in France; the Division of Rheumatology and Immunology, Cantonal Hospital St. Gallen, St. Gallen, Switzerland (A.R.-R.); and Anglia Ruskin University, Cambridge, United Kingdom (B.D.)., Lin Y; From the Hospital for Special Surgery, Weill Cornell Medical College, New York (R.F.S.), and Regeneron Pharmaceuticals, Tarrytown (A.G., M.C.N., B.A., R.B., G.D.Y.) - both in New York; the Vasculitis and Glomerulonephritis Center, Massachusetts General Hospital, Harvard Medical School, Boston (S.U.), and Sanofi, Cambridge (J.S., N.P.) - both in Massachusetts; the Division of Rheumatology, Mayo Clinic College of Medicine, Rochester, MN (K.J.W.); Sanofi, Bridgewater, NJ (W.W., Y.L.); the Department of Rheumatology and Clinical Immunology, Charité University Medicine, Berlin (F.B.); CHRU de Brest, Service de Rhumatologie, Brest (V.D.-P.), and Sanofi, Chilly-Mazarin (F.M.) - both in France; the Division of Rheumatology and Immunology, Cantonal Hospital St. Gallen, St. Gallen, Switzerland (A.R.-R.); and Anglia Ruskin University, Cambridge, United Kingdom (B.D.)., Buttgereit F; From the Hospital for Special Surgery, Weill Cornell Medical College, New York (R.F.S.), and Regeneron Pharmaceuticals, Tarrytown (A.G., M.C.N., B.A., R.B., G.D.Y.) - both in New York; the Vasculitis and Glomerulonephritis Center, Massachusetts General Hospital, Harvard Medical School, Boston (S.U.), and Sanofi, Cambridge (J.S., N.P.) - both in Massachusetts; the Division of Rheumatology, Mayo Clinic College of Medicine, Rochester, MN (K.J.W.); Sanofi, Bridgewater, NJ (W.W., Y.L.); the Department of Rheumatology and Clinical Immunology, Charité University Medicine, Berlin (F.B.); CHRU de Brest, Service de Rhumatologie, Brest (V.D.-P.), and Sanofi, Chilly-Mazarin (F.M.) - both in France; the Division of Rheumatology and Immunology, Cantonal Hospital St. Gallen, St. Gallen, Switzerland (A.R.-R.); and Anglia Ruskin University, Cambridge, United Kingdom (B.D.)., Devauchelle-Pensec V; From the Hospital for Special Surgery, Weill Cornell Medical College, New York (R.F.S.), and Regeneron Pharmaceuticals, Tarrytown (A.G., M.C.N., B.A., R.B., G.D.Y.) - both in New York; the Vasculitis and Glomerulonephritis Center, Massachusetts General Hospital, Harvard Medical School, Boston (S.U.), and Sanofi, Cambridge (J.S., N.P.) - both in Massachusetts; the Division of Rheumatology, Mayo Clinic College of Medicine, Rochester, MN (K.J.W.); Sanofi, Bridgewater, NJ (W.W., Y.L.); the Department of Rheumatology and Clinical Immunology, Charité University Medicine, Berlin (F.B.); CHRU de Brest, Service de Rhumatologie, Brest (V.D.-P.), and Sanofi, Chilly-Mazarin (F.M.) - both in France; the Division of Rheumatology and Immunology, Cantonal Hospital St. Gallen, St. Gallen, Switzerland (A.R.-R.); and Anglia Ruskin University, Cambridge, United Kingdom (B.D.)., Rubbert-Roth A; From the Hospital for Special Surgery, Weill Cornell Medical College, New York (R.F.S.), and Regeneron Pharmaceuticals, Tarrytown (A.G., M.C.N., B.A., R.B., G.D.Y.) - both in New York; the Vasculitis and Glomerulonephritis Center, Massachusetts General Hospital, Harvard Medical School, Boston (S.U.), and Sanofi, Cambridge (J.S., N.P.) - both in Massachusetts; the Division of Rheumatology, Mayo Clinic College of Medicine, Rochester, MN (K.J.W.); Sanofi, Bridgewater, NJ (W.W., Y.L.); the Department of Rheumatology and Clinical Immunology, Charité University Medicine, Berlin (F.B.); CHRU de Brest, Service de Rhumatologie, Brest (V.D.-P.), and Sanofi, Chilly-Mazarin (F.M.) - both in France; the Division of Rheumatology and Immunology, Cantonal Hospital St. Gallen, St. Gallen, Switzerland (A.R.-R.); and Anglia Ruskin University, Cambridge, United Kingdom (B.D.)., Yancopoulos GD; From the Hospital for Special Surgery, Weill Cornell Medical College, New York (R.F.S.), and Regeneron Pharmaceuticals, Tarrytown (A.G., M.C.N., B.A., R.B., G.D.Y.) - both in New York; the Vasculitis and Glomerulonephritis Center, Massachusetts General Hospital, Harvard Medical School, Boston (S.U.), and Sanofi, Cambridge (J.S., N.P.) - both in Massachusetts; the Division of Rheumatology, Mayo Clinic College of Medicine, Rochester, MN (K.J.W.); Sanofi, Bridgewater, NJ (W.W., Y.L.); the Department of Rheumatology and Clinical Immunology, Charité University Medicine, Berlin (F.B.); CHRU de Brest, Service de Rhumatologie, Brest (V.D.-P.), and Sanofi, Chilly-Mazarin (F.M.) - both in France; the Division of Rheumatology and Immunology, Cantonal Hospital St. Gallen, St. Gallen, Switzerland (A.R.-R.); and Anglia Ruskin University, Cambridge, United Kingdom (B.D.)., Marrache F; From the Hospital for Special Surgery, Weill Cornell Medical College, New York (R.F.S.), and Regeneron Pharmaceuticals, Tarrytown (A.G., M.C.N., B.A., R.B., G.D.Y.) - both in New York; the Vasculitis and Glomerulonephritis Center, Massachusetts General Hospital, Harvard Medical School, Boston (S.U.), and Sanofi, Cambridge (J.S., N.P.) - both in Massachusetts; the Division of Rheumatology, Mayo Clinic College of Medicine, Rochester, MN (K.J.W.); Sanofi, Bridgewater, NJ (W.W., Y.L.); the Department of Rheumatology and Clinical Immunology, Charité University Medicine, Berlin (F.B.); CHRU de Brest, Service de Rhumatologie, Brest (V.D.-P.), and Sanofi, Chilly-Mazarin (F.M.) - both in France; the Division of Rheumatology and Immunology, Cantonal Hospital St. Gallen, St. Gallen, Switzerland (A.R.-R.); and Anglia Ruskin University, Cambridge, United Kingdom (B.D.)., Patel N; From the Hospital for Special Surgery, Weill Cornell Medical College, New York (R.F.S.), and Regeneron Pharmaceuticals, Tarrytown (A.G., M.C.N., B.A., R.B., G.D.Y.) - both in New York; the Vasculitis and Glomerulonephritis Center, Massachusetts General Hospital, Harvard Medical School, Boston (S.U.), and Sanofi, Cambridge (J.S., N.P.) - both in Massachusetts; the Division of Rheumatology, Mayo Clinic College of Medicine, Rochester, MN (K.J.W.); Sanofi, Bridgewater, NJ (W.W., Y.L.); the Department of Rheumatology and Clinical Immunology, Charité University Medicine, Berlin (F.B.); CHRU de Brest, Service de Rhumatologie, Brest (V.D.-P.), and Sanofi, Chilly-Mazarin (F.M.) - both in France; the Division of Rheumatology and Immunology, Cantonal Hospital St. Gallen, St. Gallen, Switzerland (A.R.-R.); and Anglia Ruskin University, Cambridge, United Kingdom (B.D.)., Dasgupta B; From the Hospital for Special Surgery, Weill Cornell Medical College, New York (R.F.S.), and Regeneron Pharmaceuticals, Tarrytown (A.G., M.C.N., B.A., R.B., G.D.Y.) - both in New York; the Vasculitis and Glomerulonephritis Center, Massachusetts General Hospital, Harvard Medical School, Boston (S.U.), and Sanofi, Cambridge (J.S., N.P.) - both in Massachusetts; the Division of Rheumatology, Mayo Clinic College of Medicine, Rochester, MN (K.J.W.); Sanofi, Bridgewater, NJ (W.W., Y.L.); the Department of Rheumatology and Clinical Immunology, Charité University Medicine, Berlin (F.B.); CHRU de Brest, Service de Rhumatologie, Brest (V.D.-P.), and Sanofi, Chilly-Mazarin (F.M.) - both in France; the Division of Rheumatology and Immunology, Cantonal Hospital St. Gallen, St. Gallen, Switzerland (A.R.-R.); and Anglia Ruskin University, Cambridge, United Kingdom (B.D.).
Jazyk:	angličtina
Zdroj:	The New England journal of medicine [N Engl J Med] 2023 Oct 05; Vol. 389 (14), pp. 1263-1272.
DOI:	10.1056/NEJMoa2303452
Abstrakt:	Background: More than half of patients with polymyalgia rheumatica have a relapse during tapering of glucocorticoid therapy. Previous studies have suggested that interleukin-6 blockade may be clinically useful in the treatment of polymyalgia rheumatica. Sarilumab, a human monoclonal antibody, binds interleukin-6 receptor α and efficiently blocks the interleukin-6 pathway. Methods: In this phase 3 trial, we randomly assigned patients in a 1:1 ratio to receive 52 weeks of a twice-monthly subcutaneous injection of either sarilumab (at a dose of 200 mg) plus a 14-week prednisone taper or placebo plus a 52-week prednisone taper. The primary outcome at 52 weeks was sustained remission, which was defined as the resolution of signs and symptoms of polymyalgia rheumatica by week 12 and sustained normalization of the C-reactive protein level, absence of disease flare, and adherence to the prednisone taper from weeks 12 through 52. Results: A total of 118 patients underwent randomization (60 to receive sarilumab and 58 to receive placebo). At week 52, sustained remission occurred in 28% (17 of 60 patients) in the sarilumab group and in 10% (6 of 58 patients) in the placebo group (difference, 18 percentage points; 95% confidence interval, 4 to 32; P = 0.02). The median cumulative glucocorticoid dose at 52 weeks was significantly lower in the sarilumab group than in the placebo group (777 mg vs. 2044 mg; P<0.001). The most common adverse events with sarilumab as compared with placebo were neutropenia (15% vs. 0%), arthralgia (15% vs. 5%), and diarrhea (12% vs. 2%). More treatment-related discontinuations were observed in the sarilumab group than in the placebo group (12% vs. 7%). Conclusions: Sarilumab showed significant efficacy in achieving sustained remission and reducing the cumulative glucocorticoid dose in patients with a relapse of polymyalgia rheumatica during glucocorticoid tapering. (Funded by Sanofi and Regeneron Pharmaceuticals; SAPHYR ClinicalTrials.gov number, NCT03600818.). (Copyright © 2023 Massachusetts Medical Society.)
Databáze:	MEDLINE
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