Efficacy of Mycophenolate As a Maintenance Therapy Following the Administration of Cyclophosphamide in the Treatment of Interstitial Lung Disease Associated with Systemic Sclerosis

Javier Narváez¹, Helena Borrell Paños², Ivan Castellvi³, Sergi Heredia², Milena Millan³, Susana Herrera⁴, Eulalia Armengol², Josep María LLobet³, Joan Miquel Nolla², María Molina⁵ and Juan José Alegre⁶, ¹Rheumatology, Hospital Universitario de Bellvitge, Barcelona, Spain, ²Department of Rheumatology, Hospital Universitario de Bellvitge, Barcelona, Spain, ³Rheumatology Unit. Hospital de la Santa Creu i Sant Pau, Barcelona, Spain, ⁴Deparment of Pneumology, Hospital Universitario Dr Peset, Valencia, Spain, ⁵Department of Pneumology, Hospital Universitario de Bellvitge, Barcelona, Spain, ⁶Rheumatology Department, Hospital Universitario Doctor Peset, Valencia, Spain

Meeting: 2015 ACR/ARHP Annual Meeting

Date of first publication: September 29, 2015

Keywords: cyclophosphamide, interstitial lung disease, mycophenolate mofetil and systemic sclerosis

Session Information

Date: Tuesday, November 10, 2015

Title: Systemic Sclerosis, Fibrosing Syndromes and Raynaud's - Clinical Aspects and Therapeutics Poster III

Session Type: ACR Poster Session C

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

Background/Purpose: Treatment with cyclophosphamide (CYC) for 12 months stabilizes lung function parameters and improves respiratory symptoms of patients with systemic sclerosis and diffuse interstitial lung disease (ILD-SSc). After stopping treatment, this beneficial effect on lung function disappears at 24 months, hence the need to establish maintenance therapy after CYC. Our objective was to investigate the efficacy of mycophenolate mofetil (MMF) as a maintenance therapy following the administration of CYC in the management of ILD-SSc

Methods: An ambispective observational study was performed in 14 patients with SS (ACR/EULAR 2013 criteria) and secondary ILD confirmed by high-resolution thoracic CT (HRCT), who were treated with CYC due to severity criteria. The primary efficacy outcome was the change in pulmonary function tests (PFT) at the end of follow-up according to the following definitions from the American Thoracic Society: a) improvement: if an increase in FVC ≥ 10% or DLCO ≥ 15% is observed; b) stabilization: if changes in FVC are less than 10% or 15% in DLCO; and c) worsening:if FVC decreases ≥ 10% or DLCO ≥ 15%.

Results: Of the 14 included patients (12 women, mean age 58 ± 10 years), 11 had diffuse SS, one had limited SS, and two had systemic sclerosis sine scleroderma.

Regarding ILD subtypes, 13 cases corresponded to NSIP (nonspecific interstitial pneumonitis; two of them fibrosing) and one to UIP (usual interstitial pneumonitis). All had been treated with intravenous CYC having achieved, at minimum, stabilized lung function parameters: 10 patients had been administered CFM for a minimum of 12 months (six monthly boluses, followed by two to four quarterly boluses) and four patients for six months (six monthly boluses). The dose administered in the bolus was 750 mg/m² or 500 mg/m²body surface as tolerated. MMF doses ranged from 1.5 to 2 g per day.

During follow-up, nine (64%) patients showed ILD-SSc progression with clinical and functional decline, ultimately requiring rescue treatment with rituximab (RTX). The elapsed time from the start of MMF to treatment with RTX (mean ± SD) was 21 ± 8 months (range, 8-28). The evolution of PFT values in this subgroup of patients is shown in the following table:

	Baseline (onset of MMF treatment	End of MMF treatment	% of change from baseline
FVC %	65.7 ± 20.5	51.2 ± 18.4	-22.07%
TLC %	69.2 ± 10.9	61.6 ± 9.2	-10.98%
DLCO%	51.8 ± 15.5	40.2 ± 13.6	-22.39%

In the four (36%) remaining patients, MMF stabilized PFT. The mean follow-up time in this subgroup was 18 ± 8 months (range, 8-28).

Conclusion: Maintenance therapy with MMF only manages to preserve the beneficial effect achieved with CYC in approximately one-third of cases. Despite advances in the early diagnosis of ILD-SSc, the results obtained with available treatments remain disappointing.

Disclosure: J. Narváez, None; H. Borrell Paños, None; I. Castellvi, None; S. Heredia, None; M. Millan, None; S. Herrera, None; E. Armengol, None; J. M. LLobet, None; J. M. Nolla, None; M. Molina, None; J. J. Alegre, None.

To cite this abstract in AMA style:

Narváez J, Borrell Paños H, Castellvi I, Heredia S, Millan M, Herrera S, Armengol E, LLobet JM, Nolla JM, Molina M, Alegre JJ. Efficacy of Mycophenolate As a Maintenance Therapy Following the Administration of Cyclophosphamide in the Treatment of Interstitial Lung Disease Associated with Systemic Sclerosis [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/efficacy-of-mycophenolate-as-a-maintenance-therapy-following-the-administration-of-cyclophosphamide-in-the-treatment-of-interstitial-lung-disease-associated-with-systemic-sclerosis/. Accessed .

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