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Ann Rheum Dis. 2019 Jul;78(7):979-987. doi: 10.1136/annrheumdis-2018-214816. Epub 2019 Apr 9.

Outcomes of patients with systemic sclerosis treated with rituximab in contemporary practice: a prospective cohort study.

Collaborators (230)

Guiducci S, Walker UA, Kyburz D, Lapadula G, Maurer B, Jordan S, Dobrota R, Becvar R, Sierakowsky S, Bielecka OK, Sulli A, Cutolo M, Cuomo G, Nicoara I, Kahan A, Vlachoyiannopoulos PG, Montecucco CM, Caporali R, Stork J, Inanc M, Carreira PE, Novak S, Czirják L, Varju C, Kucharz EJ, Kotulska A, Kopec-Medrek M, Widuchowska M, Cozzi F, Rozman B, Mallia C, Coleiro B, Gabrielli A, Farge D, Wu C, Marjanovic Z, Faivre H, Hij D, Dhamadi R, Wollheim F, Scheja A, Wuttge DM, Andréasson K, Martinovic D, Balbir-Gurman A, Trotta F, Monaco AL, Pellerito R, Mauriziano O, Caramaschi P, Morovic-Vergles J, Black C, Denton C, Damjanov N, Henes J, Santamaria VO, Heitmann S, Krasowska Matthias D, Hasler P, Burkhardt H, Himsel A, Bajocchi G, Pereira Da Silva JA, Salvador MJ, Stamenkovic B, Stankovic A, Selmi CF, Santis M, Tikly M, Denisov LN, Müller-Ladner U, Frerix M, Tarner I, Scorza R, Puppo F, Engelhart M, Strauss G, Nielsen H, Damgaard K, Szücs G, Mendoza AZ, Puente C, Sifuentes Giraldo WA, Midtvedt Ø, Reiseter S, Garen T, Launay D, Valesini G, Ionescu RM, Groseanu L, Opris D, Cornateanu RS, Ionitescu R, Gherghe AM, Soare A, Gorga M, Bojinca M, Milicescu M, Sunderkötter C, Kuhn A, Sandorfi N, Schett G, Beyer C, Meroni P, Ingegnoli F, Mouthon L, Keyser F, Melsens K, Cantatore FP, Corrado A, Iversen L, Mühlen CAV, Bohn JM, Lonzetti LS, Eyerich K, Hein R, Knott E, Wiland P, Szmyrka-Kaczmarek M, Sokolik R, Morgiel E, Madej M, Houssiau FA, Krummel-Lorenz B, Saar P, Aringer M, Günther C, Westhovens R, Lenaerts J, Anic B, Baresic M, Mayer M, Üprus M, Otsa K, Granel B, Müller CS, Radominski SC, Azevedo VF, Jimenez S, Busquets J, Agachi S, Groppa L, Chiaburu L, Russu E, Popa S, Zenone T, Pileckyte M, Mathieu A, Vacca A, Sampaio-Barros PD, Yoshinari NH, Marangoni RG, Martin P, Fuocco L, Stebbings S, Highton J, Chapman P, O'Donnell J, Stamp L, Doube A, Solanki K, Veale D, O'Rourke M, Loyo E, Li M, Abdel Atty Mohamed WA, Amoroso A, Gigante A, Oksel F, Yargucu F, Tanaseanu CM, Popescu M, Dumitrascu A, Tiglea I, Foti R, Chirieac R, Furst D, Villiger P, Adler S, Laar JV, Kayser C, Fathi N, Hassanien M, de la Peña Lefebvre PG, Rubio SR, Exposito MV, Chatelus E, Sibilia J, Gottenberg JE, Chifflot H, Litinsky I, Emery P, Buch M, Galdo FD, Venalis A, Butrimiene I, Venalis P, Rugiene R, Karpec D, Lasky JA, Cosentino V, Kerzberg E, Montoya F, Bianchi W, Carneiro S, Maretti GB, Bianchi DV, Limonta M, Brucato AL, Lupi E, Rosner I, Rozenbaum M, Slobodin G, Boulman N, Rimar D, Couto M, Kahl S, Chen F, McCloskey D, Malveaux H, Spertini F, Ribi C, Buss G, Martin T, Guffroy A, Poindron V, Chotchaeva F, Mukhin NA, Moiseev S, Herrick A.

Author information

1
Rheumatology A Department, Paris Descartes University, Cochin Hospital, Paris, France muriel-elhai@hotmail.fr.
2
Unit of Clinical Research, Paris Seine Saint Denis University, Bobigny, France.
3
Center of Experimental Rheumatology, Zurich, Switzerland.
4
Rheumatology and Internal Medicine, Ghent University Hospital, Ghent, Belgium.
5
Unit for Molecular Immunology and Inflammation, VIB Inflammation Research Center (IRC), Ghent, Belgium.
6
Department of Internal Medicine, University of Florence, Firenze, Italy.
7
Rheumatology, Hospital Peset, Valencia, Spain.
8
Rheumatology Department, Bordeaux University Hospital, Bordeaux, France.
9
B. Shine Department of Rheumatology, Rambam Health Care Campus and Technion, Haifa, Israel.
10
Interdisciplinary Department of Medicine-Rheumatology Unit, Policlinico, University of Bari, bari, Italy.
11
Clinic of Nephrology, Internal and Occupational Diseases, Sechenov First Moscow State Medical University, Moscow, Russian Federation.
12
Internal Medicine, CHU south hospital, RENNES, France.
13
Rheumatology, Charit University Hospital, Berlin, Germany.
14
Hospital de la Santa Creu i Sant Pau, Barcelona, Spain, Barcelona, Spain.
15
Rheumatology and Clinical Immunology Service, Spedali Civili di Brescia, Brescia, Italy.
16
Rheumatology Department, Second University of Naples, Naples, Italy.
17
Laboratory of Tissue Homeostasis and Disease, Skeletal Biology and Engineering Research Center, Department of Development and Regeneration, KU Leuven, Leuven, Belgium.
18
Univ. Lille, Inserm, CHU Lille, U995 - LIRIC - Lille Inflammation Research International Center, Service de Médecine Interne, Hôpital Claude Huriez, Centre de Référence pour la Sclérodermie Systémique, FHU IMMInENT, F-59000, Lille, France.
19
Division of Rheumatology Department of Medicine III, Technical University of Dresden, Dresden, Germany.
20
Institute of Rheumatology, Russian Academy of Medical Science, Moscow, Russian Federation.
21
Internal Medicine, Rheumatology, Immunology and Nephrology, Asklepios Clinic Altona, Hamburg, Germany.
22
Rheumatology, Hospital General Universitario Gregorio Marañón, Madrid, Spain.
23
Department of Internal Medicine III, University of Erlangen, Erlangen, Germany.
24
Department of Dermatology, University of Cologne, Cologne, Germany.
25
Department of Rheumatology, Rikshospitalet University Hospital, Oslo, Norway.
26
Clinical Medicine and Therapy, Sapienza University of Rome, Rome, Italy.
27
Rutgers-Robert Wood Johnson Medical School Scleroderma Program, New Brunswick, New Jersey,USA.
28
Dipartimento di Medicina, Ospedale San Gerardo, Monza, Italy.
29
Rheumatology 2 Department, Universitatea de Medicina si Farmacie Gr T Popa Iasi Facultatea de Medicina, Iasi, Romania.
30
Centroper la Sclerosi Sistemica -Dipartimento di Medicina Clinica, Università LaSapienza, Rome, Italy.
31
Internal Medicine and Rheumatology Department, Cantacuzino Hospital, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania.
32
Allergy and Rheumatology, Nippon Medical School Graduate School of Medicine, Tokyo, Japan.
33
University Medical Center Comprehensive Pulmonary Hypertension Center (UMC-CPHC); Tulane University Lung Center Tulane, New Orleans Scleroderma and Sarcoidosis Patient Care and Research Center New Orleans, New Orleans, Louisiana, USA.
34
Division of Immunology and Allergy, HCUGE, Geneva, Switzerland.
35
Department of Rheumatology, Lund University, Lund, Sweden.
36
University Hospital of Copenhagen, Department of Dermatology, Hospital Bispebjerg, Copenhagen, Denmark.
37
Department of Rheumatology, University of Marmara, Istanbul, Turkey.
38
Clinica Reumatologie, Cluj-Napoca, Romania.
39
Rheumatology Unit, University of Verona, Verona, Italy.
40
URC CRC, Hopital Avicenne, Bobigny, France.
41
Rheumatology A Department, Cochin Hospital, APHP, Paris Descartes University, Paris, France.

Abstract

OBJECTIVE:

To assess the safety and efficacy of rituximab in systemic sclerosis (SSc) in clinical practice.

METHODS:

We performed a prospective study including patients with SSc from the European Scleroderma Trials and Research (EUSTAR) network treated with rituximab and matched with untreated patients with SSc. The main outcomes measures were adverse events, skin fibrosis improvement, lung fibrosis worsening and steroids use among propensity score-matched patients treated or not with rituximab.

RESULTS:

254 patients were treated with rituximab, in 58% for lung and in 32% for skin involvement. After a median follow-up of 2 years, about 70% of the patients had no side effect. Comparison of treated patients with 9575 propensity-score matched patients showed that patients treated with rituximab were more likely to have skin fibrosis improvement (22.7 vs 14.03 events per 100 person-years; OR: 2.79 [1.47-5.32]; p=0.002). Treated patients did not have significantly different rates of decrease in forced vital capacity (FVC)>10% (OR: 1.03 [0.55-1.94]; p=0.93) nor in carbon monoxide diffusing capacity (DLCO) decrease. Patients having received rituximab were more prone to stop or decrease steroids (OR: 2.34 [1.56-3.53], p<0.0001). Patients treated concomitantly with mycophenolate mofetil had a trend for better outcomes as compared with patients receiving rituximab alone (delta FVC: 5.22 [0.83-9.62]; p=0.019 as compared with controls vs 3 [0.66-5.35]; p=0.012).

CONCLUSION:

Rituximab use was associated with a good safety profile in this large SSc-cohort. Significant change was observed on skin fibrosis, but not on lung. However, the limitation is the observational design. The potential stabilisation of lung fibrosis by rituximab has to be addressed by a randomised trial.

KEYWORDS:

lung fibrosis; rituximab; skin fibrosis; systemic sclerosis

Conflict of interest statement

Competing interests: OD has consultancy relationship with Actelion, Bayer, BiogenIdec, Boehringer Ingelheim, ChemomAb, espeRare foundation, Genentech/Roche, GSK, Inventiva, Italfarmaco, Lilly, medac, MedImmune, Mitsubishi Tanabe Pharma, Pharmacyclics, Novartis, Pfizer, Sanofi, Sinoxa and UCB in the area of potential treatments of scleroderma and its complications. OD has received research funding from Actelion, Bayer, Boehringer Ingelheim, Mitsubishi Tanabe Pharma and Roche in the area of potential treatments of scleroderma and its complications. In addition, OD has a patent mir-29 for the treatment of systemic sclerosis licensed. M-ET has received consulting fees, speaking fees or honoraria from Abbvie, BMS, Lilly, Medac, MSD, Pfizer, Roche and UCB. PA has received travel expenses from Roche (<2500€). SV received speaking fees by Pfizer, Abbvie, Bristol-Myers Squibb, consultant fee from Thermofischer and Boehringer-Ingelheim Italia and Educational support from Pfizer, Roche, BMS. EH has received speaker fees and/or honoraria for consultations from Roche, less than 10 000€. NH received lecture fees from Actelion Pharmaceuticals, Pfizer, Roche and grant support from Actelion and Bayer Pharmaceuticals. CM has/had consultancy relationship and/or has received honoraria from Actelion, Abbvie, Roche and Geneva Romfarm in the area of systemic sclerosis and its complications. CC has received travel grants from Roche. YA has/had consultancy relationship and/or has received grants from Actelion, Bayer, BMS, Boehringer-Ingelheim, Inventiva, Roche, Sanofi-Aventis in the area of systemic sclerosis.

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