Intensified B-Cell Depletion Therapy in Progressive Systemic Sclerosis Patients: 24 Months Follow-up

Daniela Rossi¹, Irene Cecchi², Massimo Radin³, Elena Rubini⁴, Savino Sciascia⁵ and Dario Roccatello⁶, ¹Department of Medicine and Experimental Oncology, CMID - Center of Research of Immunopathology and Rare Diseases, Turin, Italy, ²Center of Research of Immunopathology and Rare Diseases- Coordinating Center of Piemonte and Valle d’Aosta Network for Rare Diseases, Department of Clinical and Biological Sciences, University of Turin, Italy, Turin, Italy, ³Department of Clinical and Biological Sciences, Center of Research of Immunopathology and Rare Diseases- Coordinating Center of Piemonte and Valle d’Aosta Network for Rare Diseases, Department of Clinical and Biological Sciences, University of Turin, Italy, Turin, Italy, ⁴Center of Research of Immunopathology and Rare Diseases- Coordinating Center of Piemonte and Valle d’Aosta Network for Rare Diseases, Department of Clinical and Biological Sciences, University of Turin and S. Giovanni Bosco Hospital, Turin, Italy., Turin, Italy, ⁵Center of Research of Immunopathology and Rare Diseases- Coordinating Center of Piemonte and Valle d’Aosta Network for Rare Diseases, Department of Clinical and Biological Sciences, University of Turin, Italy, Center of Research of Immunopathology and Rare Diseases- Coordinating Center of Piemonte and Valle d’Aosta Network for Rare Diseases, Department of Clinical and Biological Sciences, University of Turin, Italy, Torino, Italy, ⁶Center of Research of Immunopathology and Rare Diseases- Coordinating Center of Piemonte and Valle d’Aosta Network for Rare Diseases, Department of Clinical and Biological Sciences, University of Turin and S. Giovanni Bo, Turin, Italy

Meeting: ACR/ARHP Annual Meeting 2018

Keywords: Biologic drugs, Immunotherapy, pulmonary fibrosis, rituximab and systemic sclerosis

Session Information

Date: Monday, October 22, 2018

Title: Systemic Sclerosis and Related Disorders – Clinical Poster II

Session Type: ACR Poster Session B

Session Time: 9:00AM-11:00AM

Background/Purpose:

Systemic sclerosis (SSc) is a connective tissue autoimmune disease with systemic involvement and a serious medical condition with a high rate of mortality, especially due to interstitial lung disease (ILD).The exact pathophysiology is still unclear, but B cells seem to play a crucial role in the initiation and the progression of the disorder. Therefore, the use of Rituximab (RTX) might have a rational in the treatment of SSc.

Methods:

We retrospectively collected data from SSc patients resistant or intolerant to previous therapies, treated with intensified B-depletion therapy, between 2013 and 2016. Therapeutic protocol comprehends: RTX 375 mg/sm on days 1, 8, 15, 22, and two more doses after one and two months, associated with two intravenous administrations of 10mg/kg of cyclophosphamide and three methylprednisolone pulses (15 mg/kg) followed by oral prednisone (0.8mg/kg/day, rapidly tapered to 5mg/day by the end of the 3^rd month after RTX).

Results:

The study included 20 SSc patients (18 females and 2 males; mean age 66.7 ±11.0 years). Patients presented with severe multiorgan involvement: ILD (19/20, 95%), pulmonary hypertension (12/20, 60%), and skin thickening (17/20, 85%). After a follow-up of 24 months, we observed a decrease in the levels of NT-proBNP (mean baseline: 385.4±517, mean at 24 months: 283±648, p< 0.05), and in the Modified Rodnan Skin Score (mRSS) (mean mRSS baseline: 14.4 ±10.5, mean after 24 months of follow-up: 12.9 ±10, p<0.05). Four out 19 (21%) patients experienced a significant improvement of ILD, as assessed by high-resolution computed tomography, while in 12/19 (63%) patients the intensified B-cell depletion therapy was associated with a stabilization of the imaging features with no sign of progression. Three out of 19 (16%) patients showed a deterioration of the ILD.

Patients showed no significant decrease in forced vital capacity (FVC) (mean baseline FVC: 93.6 ±19.3, mean after 24 months of follow-up: 92.2 ±23.3), no significant decrease in forced expiratory volume in one second (FEV1) (mean baseline FEV1: 89.5±15.6, mean FEV1 at 24 months: 87±21.2), no significant decrease in diffusing capacity (DLCO) (mean baseline DLCO values: 58.8±8.6, mean at 24 months: 60.3±14), no significant change in the ejection fraction (EF) (mean baseline EF values: 62.8±6.4, mean EF values at 24 months: 58.6±7.1) and in pulmonary artery pressure (PAP) (mean baseline PAP: 30.2 ±10.5, mean at 24 months: 31.1 ±11.05).

Conclusion:

Our data suggest that the intensified B-depletion therapy protocol might represent a promising tool for the management of SSc in terms of controlling the progression of the disease, especially when considering pulmonary and skin manifestations.

Disclosure: D. Rossi, None; I. Cecchi, None; M. Radin, None; E. Rubini, None; S. Sciascia, None; D. Roccatello, None.

To cite this abstract in AMA style:

Rossi D, Cecchi I, Radin M, Rubini E, Sciascia S, Roccatello D. Intensified B-Cell Depletion Therapy in Progressive Systemic Sclerosis Patients: 24 Months Follow-up [abstract]. Arthritis Rheumatol. 2018; 70 (suppl 9). https://acrabstracts.org/abstract/intensified-b-cell-depletion-therapy-in-progressive-systemic-sclerosis-patients-24-months-follow-up/. Accessed .

ACR Meeting Abstracts - https://acrabstracts.org/abstract/intensified-b-cell-depletion-therapy-in-progressive-systemic-sclerosis-patients-24-months-follow-up/