Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement

Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.


A Randomized, Controlled, Multicenter Phase III Study of the Efficacy and Safety of Rituximab (RTX) Monotherapy Versus the Best Available Treatment in Patients with Mixed Cryoglobulinemia Syndrome.

De Vita15,  Salvatore, Quartuccio15,  Luca, Isola8,  Miriam, Masolini16,  Paola, Sacco15,  Stefania, De Marchi15,  Ginevra, Mazzaro6,  Cesare

A.O. Maggiore-Medicina II, Novara, Italy
Internal Medicine Unit, Saronno Hospital, Azienda Ospedaliera di Busto Arsizio, Saronno, VA, Italy, Italy
Internal Medicine, Donizetti Hospital, Monza, Italy, Italy
Internal Medicine, Università Politecnica delle Marche, Ancona, Italy, Italy
Nephrology Unit, Spedali Riuniti, Brescia, Italy, Italy
Rheumatology Clinic, A.O. Niguarda Ca' Granda Hospital, Milan, Italy
Rheumatology Clinic, Azienda Ospedaliero-Universitaria "S. Maria della Misericordia", Udine, Italy
Rheumatology Clinic, Azienda Ospedaliero-Universitaria "S. Maria della Misericordia", Udine, Italy
Rheumatology Clinic, University of Naples, Italy, Italy
Rheumatology Unit, Department of Internal Medicine, University of Modena e Reggio Emilia, Italy, Italy
Rheumatology Unit, Department of Internal Medicine, University of Modena, Italy, Italy
Center for Systemic Manifestations of Hepatitis Viruses (MaSVE), Department of Internal Medicine, University of Florence, Florence, Italy
Rheumatology Unit, Department of Internal Medicine, University of Pisa, Pisa, Italy, Italy
Rheumatology Unit, M. Scarlato Hospital, Scafati, Salerno, Italy, Italy
Centro di Ricerche di Immunopatologia e Documentazione su Malattie Rare, Struttura Complessa a Direzione Universitaria di Immunologia Clinica, Ospedale S.G. Bosco, Torino, Italy
Department of Clinical Medicine, University of Bologna, S. Orsola-Malpighi Hospital, Bologna, Italy
Department of Infectious Diseases and Immunology, Cotugno Hospital, Naples, Italy
Department of Internal Medicine, Pordenone General Hospital, Pordenone, Italy
Dipartimento di Scienze Cliniche Luigi Sacco, Sezione di Malattie Infettive e Immunopatologia, Università degli Studi, Ospedale Luigi Sacco, Milano, Italy
Institute of Statistics, University of Udine, Udine, Italy, Italy
Internal Medicine Unit, Policlinico San Marco, Bergamo, Italy, Italy

Objectives:

this is the first randomized controlled trial comparing RTX with the best available treatments (i.e., cyclophosphamide, azathioprine, high-dose steroids, or plasma exchange) in MC patients with glomerulonephritis, or peripheral neuropathy or skin ulcers, where antiviral therapy failed or was contraindicated by the expert clinician. Primary end point was to evaluate the survival on treatment (due to lack of treatment failure) on RTX in comparison with the best available treatment options (as chosen by expert clinicians) on major manifestations of MC.

Patients and Methods:

59 MC patients were enrolled; 30 patients were randomized in the arm A (best available treatments), 10 nephritis, 3 skin ulcers and 17 peripheral neuropathy, while 29 patients were randomized in the arm B (RTX), 7 nephritis, 3 skin ulcers and 17 peripheral neuropathy. RTX 1 g × 2 at day 1 and 15 was administered with standard premedication. Patients were followed for 24 months. Rescue arm with RTX for non-responders to the best available treatment was permitted in any time, while withdrawn due to RTX treatment failure was introduced at the 6th month after RTX, if no response was observed. Finally, RTX retreatment was given at the time of clinical relapse.

Results:

Fifty-seven patients were available for data analyses. Patients were HCV positive in 53/57 (93%), they were 46 female and 11 male, and median age was 65 years (range 37–79 years). No differences between the two randomized groups were observed in terms of age and sex distribution.

Treatment chosen in group A were: high-doses of corticosteroids in 17/29 (58.6%), plasmapheresis in 5/29 (17.2%), cyclophosphamide in 4/29 (13.8%) and azathioprine in 3/29 (10.3%).

Average survival time on treatment was (mean±SE) 76.9 ± 24.2 days on group A, while it was 529.1 ± 40.5 days in group B (p<0.0001, log Rank test). Survival rate on treatment in group B vs group A was 93% vs 14% at month +3, 3% vs 71% at month +6, 3% vs 64% at month +12, and 61% vs 3% at month +24.

When considering the following variables in a multivariate regression model (age, sex, baseline BVAS, and the baseline clinical manifestations, as defined as skin ulcers, and/or glomerulonephritis and/or neuropathy, and the treatment group), only the assigned treatment group was selected and significantly associated with the survival time on treatment (p=0.0001, OR: 7.9; 95% CI: 3.6–17.2), thus confirming the association between the survival on treatment and the assignment to the rituximab group.

Conclusion:

RTX is the best choice in MC patients with active major involvements (i.e. renal, neurologic or cutaneous), when antiviral therapy failed or is contraindicated. The RTX 1 g × 2 treatment schedule was alternative to the standard hematologic regimen of 4 weekly 375 mg/m2 infusions.

To cite this abstract, please use the following information:
De Vita, Salvatore, Quartuccio, Luca, Isola, Miriam, Masolini, Paola, Sacco, Stefania, De Marchi, Ginevra, et al; A Randomized, Controlled, Multicenter Phase III Study of the Efficacy and Safety of Rituximab (RTX) Monotherapy Versus the Best Available Treatment in Patients with Mixed Cryoglobulinemia Syndrome. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :2201
DOI: 10.1002/art.29965

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