AB0634 Rituximab in systemic sclerosis-interstitial lung disease, a case series of 18 patients

Abstract

BackgroundInterstitial lung disease (ILD) is a severe complication of systemic sclerosis (SSc). Immunosuppressives such as cyclophosphamide (CYC) and mycophenolate mophetil (MMF) are used in its treatment with no proven efficacy (1). Rituximab (RTX) appears to be an emerging agent according to case series.ObjectivesThis retrospective study aims to evaluate the efficacy of RTX on SSc-ILD in a group of patients followed in our center.MethodsA chart review revealed 18 patients (16 women, 2 men; mean age 50.3±12.1 SD years (range 30–72), mean disease duration 8.3±9.3 SD years) with SSc who have been diagnosed as having ILD (confirmed by high-resolution thorax computed tomography and pulmonary function tests) and have been treated with one or more cycles of RTX. Efficacy was evaluated according to the criteria of the American Thoracic Society: improvement= an increase in FVC≥10% or DLCO≥15%; worsening= a decrease in FVC≥10% or DLCO≥15%; stabilization= changes in FVC less than 10% or DLCO less then 15% (2).ResultsTable 1Demographic findings of the patients and their response to RTX treatmentGroup 1Group 2All patients (ILD with short duration and naive to treatment)(ILD with long duration and previous IS therapy) Number of patients4 (22.2%)14 (77.7%)18Sex (F/M)3/113/116/2Mean disease duration2±0.8 SD years10.2±9.8 SD years8.3±9.3 SD yearsFollow-up time after initiation of RTX12.2±6.8 SD months21±12.4 SD months19±11.8 SD monthsBaseline FVC%69.2±20.965.1±14Last FVC%66.7±1361.6±19.6Baseline DLCO%57.7±24.143.5±12.2Last DLCO%52±1841.2±21.8Outcome: Stable/Improvement (n)279Worsening (n)257Death011Unable to do PFT (n)011Four patients were treatment naive for ILD when they received RTX (Group 1). The mean duration between the diagnosis of ILD and RTX treatment in Group 1 was 3.5 months (range 0–14 months). The average RTX cycle in this group was 2 with 1 patient also receiving mycophenolate mophetil in combination with RTX. The mean follow-up time after the initiation of RTX in this group was 12.2±6.8 SD months (range 7–22 months). FVC/DLCO was stable or improved in 2/4 compared to baseline and worsened in 2/4 at the end of follow-up at group 1.Fourteen patients had a 10.2 years-history of SSc and have been treated with immunosuppressives (cyclophosphamide, azathioprine, methotrexate, MMF) for ILD before RTX (Group 2). The mean duration between the diagnosis of ILD and RTX treatment in Group 2 was 71.2 months (range 5–246 months). These patients received a mean of 3 cycles of RTX with 5 receiving MMF (n=3) or AZA (n=2) in addition to RTX. One patient died after 3 months following the first RTX cycle (unknown reason) and 1 was unsuitable for spirometry because of microstomia. Of the remaining 12 patients in Group 2, improvement or stabilisation was seen in 7 and worsening was seen in the remaining 5 patients.ConclusionsRTX appears to be modestly effective for ILD of SSc. The duration of ILD as well as the presence or absence of previous immunosuppressive therapy do not appear as playing a role in response.References Avouac J et...

Open questions on the management of targeted therapies for the treatment of systemic sclerosis-interstitial lung disease: results of a EUSTAR survey based on a systemic literature review

“…Among the 34 studies investigating the role of RTX in SSc, 15 , 19 – 52 a total of 1001 patients (691 SSc-ILD patients) were evaluated: median number of 18 patients per study (11–30). The overall level of evidence for RTX in SSc-ILD patients is low as most of the studies were classified as level 3b and level 4 according to the Oxford scale, only the RCT 45 was classified as level 2b.…”

“…Four different RTX treatment regimens were described. A control group was present in 14 studies (41%) which included standard of care medications, 19 , 29 , 31 – 33 , 39 , 42 , 47 cyclophosphamide, 20 , 38 , 48 , 49 and placebo. 45 In one study, the control group included the same group of patients before RTX therapy.…”

“…The 3-month follow-up was available in four studies (12%). 19,24,33,38 A statistically significant improvement of the predicted delta FVC was observed in a single study, 38 whereas a statistically significant change of the median predicted DLCO was reported in only two studies 24,38 (a decrease and an improvement in delta predicted DLCO of 8.5%, respectively).…”