The purpose of this study is to determine whether Rituximab is safe and effective as a maintenance strategy in individuals with stabilized systemic sclerosis in adults.
Systemic sclerosis (SSc) is a rare autoimmune connective tissue-disease. Interstitial lung disease (ILD) is a common manifestation and a leading cause of death in SSc. Rituximab (RTX) is commonly used in SSc-ILD induction treatment and recent trials have now fully demonstrated its safety and efficacy as an induction treatment. The DESIRES trial reported that RTX-induction was associated with a 24-week stabilization of FVC. As evaluated by the FVC at 24 weeks from baseline, 25 patients with SSc-ILD treated with RTX were significantly improved compared with 23 patients treated with placebo (0.09% vs -2.87%; \[95%CI 0.08-5.84\]; p \< 0.05). Recently, the RECITAL trial showed the absence of difference between induction treatment with cyclophosphamide (CYC) and RTX in ILD including SSc-ILD. Indeed, both RTX and CYC resulted in an improvement in FVC (97 ± 234mL and 99 ± 329mL respectively) at 24 weeks, without significant statistical difference in 101 subjects. Furthermore, the EVER-ILD study, also very recently presented, reported a beneficial of RTX in addition to mycophenolate mofetil (MMF) over RTX in CTD-ILD. Altogether with previous European database studies which analyzed the very common usage of RTX as induction therapy in SSc, these studies have confirmed its efficient and safe role as an induction treatment in SSc-ILD. Still, the impact of re-treatment with RTX in maintaining ILD-stabilization has never been studied and deserve to be studied. The hypothesis that drives the MAINRITSyS is that RTX maintains ILD stabilization in SSc-ILD.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
120
Cochin Hospital
Paris, Île-de-France Region, France
changes in forced vital capacity (FVC) from baseline to Month 18 of randomisation.
PFTs: changes in forced vital capacity (FVC)
Time frame: 18 months
Mortality up to 18 months
Time frame: 18 months
Occurrence of Adverse Events
Occurrence of adverse events, overall and occurring at time of perfusion (day 0, and 6, 12 and 18 months)
Time frame: At 6, 12 and 18 months
Occurrence of Adverse Events
The number of adverse events, expressed according to the Common Terminology Criteria for Adverse Events (CTCAE): CTCAE toxicity grading system per patient-year at month 6, 12, and 18, for the following adverse events combined: death (all causes), grade 2 or higher leukopenia or thrombocytopenia, grade 3 or higher infections, hospitalization resulting either from the disease or from a complication due to the study treatment.
Time frame: At 6, 12 and 18 months
Occurrence of AE of specific interest previously mentioned at 6, 12 and 18 months
Time frame: At 6, 12 and 18 months
Change in gammaglobulin, lymphocytes and CD19 levels at 6, 12 and 18 months
Time frame: At 6, 12 and 18 months
Change from baseline in DLCO over 6, 12, and 18 months
Time frame: At 6, 12 and 18 months
Change from baseline in TLC over 6, 12, and 18 months
Time frame: At 6, 12 and 18 months
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Further analyses on TLC
Absolute categorical change of % TLC at 6, 12 and 18 months (decrease by \>5%, increase by \>5% and change within \<5%) Absolute categorical change of % TLC at 6, 12 and 18 months (decrease by \>10%, increase by \>10% and change within \<10%)
Time frame: At 6, 12 and 18 months
Change from in 6-min walk test distance over 6, 12 and 18 months
Time frame: At 6, 12 and 18 months
Further analyses on FVC
* Absolute categorical change of % FVC at 6, 12 and 18 months (decrease by \>5%, increase by \>5% and change within \<5%) * Absolute categorical change of % FVC at 6, 12 and 18 months (decrease by \>10%, increase by \>10% and change within \<10%)
Time frame: At 6, 12 and 18 months
Progression-free survival (composite endpoint of mortality, transplant, treatment failure or decline in FVC >10% compared to baseline) over 6, 12 and 18 months
Time frame: At 6, 12 and 18 months
Treatment failure (as determined by need for transplant or rescue therapy) at 6, 12 and 18 months
Time frame: At 6, 12 and 18 months
INBUILD progression (as determined by the INBUILD criteria for ILD progression(73)) at 6, 12 and 18 months
Time frame: At 6, 12 and 18 months
Change from baseline in capillary oxygen saturation (SpO2) at 6, 12 and 18 months
Time frame: At 6, 12 and 18 months
Changes from baseline to 18 months in HRCT of chest images
Time frame: At 18 months
Proportions of patients who achieved 20%, 30%, 40%, 50% ,60%, 70%, 80%, 90% and 100% response criteria according to revised CRISS at 6, 12 and 18 months
Time frame: At 6, 12 and 18 months
Changes in physicians visual analogue scales over 18 months.
These scales range from 0 (minimum) to ten (maximum) points and will be performed at day 0, at 6, 12, and 18 months. Higher score mean worse outcome
Time frame: at 0, 6, 12, 18 months
Changes in patients' visual analogue scales over 18 months.
These scales range from 0 (minimum) to ten (maximum) points and will be performed at day 0, at 6, 12, and 18 months. Higher score mean better outcome
Time frame: At 0, 6, 12, and 18 months
Changes in mRSS at 6, 12, and 18 months
Higher score mean worse outcome.
Time frame: At 6, 12 and 18 months
Proportion of patients who improved mRSS at 6, 12 and 18 months after randomisation.
Time frame: At 6, 12 and 18 months
Proportion of patients with an active disease according to the European scleroderma trials and research group (EUSTAR) SSc activity index at 6, 12 and 18 months after randomisation
Time frame: At 6, 12 and 18 months
Saint Georges Respiratory Hospital Questionnaire at day 0, and at 6, 12, and 18 months after randomisation.
These questionnaires are self-administered questionnaires assessing the perception of lung disease by the patients. These scales range from 0 (minimum) to one hundred (maximum) points. Higher score mean worse outcome
Time frame: At 0, 6, 12 and 18 months
King Brief's Interstitial Lung Disease questionnaire at day 0, and at 6, 12, and 18 months after randomisation.
These questionnaires are self-administered questionnaires assessing the perception of lung disease by the patients. These scales range from 0 (minimum) to 100 (maximum) points. Higher score mean better outcome
Time frame: at 0, 6, 12, and 18 months
Short Form-36 (SF-36) health questionnaire
SF36 : 0 à 100 - These scales range from 0 (minimum) to 100 (maximum) points. Higher score mean better outcome - to assess Quality of life
Time frame: At 0, 6, 12 and 18 months
EuroQol-5 Domain (EQ5D5L) health questionnaire
EQ5D5L : The EQ-5D-5L instrument comprises five dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension is rated on a five-point scale, from 1 (no problems) to 5 (extreme problems), with higher scores reflecting worse health status. To assess quality of life.
Time frame: At 0, 6, 12 and 18 months
Scleroderma skin patients reported outcome (SSPRO) at day 0, and at 6, 12 and 18 months after randomisation.
Time frame: At 0, 6, 12 and 18 months
HAQ-DI and SHAQ scales at day 0, and at 6, 12 and 18 months after randomisation. These scales range from 0 (minimum) to 3 (maximum) points. Higher score mean worse outcome
Time frame: At 0, 6, 12 and 18 months
Total corticosteroid requirement at 6, 12 and 18 months
Time frame: At 6, 12 and 18 months
Levels of prespecified biomarkers (KL-6, SP-D, MUC1, SFTPD, CCL18 and CXCL4) at months 6, 12 and 18 months.
Time frame: At 6, 12 and 18 months
Presence of anti-RTX-antibody at months 6, 12 and 18.
Time frame: At 6, 12 and 18 months
Dosage of plasma and serum residual concentration of RTX at months 6, 12 and 18
Time frame: At 6, 12 and 18 months
Hospitalisation for respiratory cause over the duration of the trial
Time frame: At 18 months
Time to first hospitalisation for respiratory cause
Time frame: At 18 months
Time to death
Time frame: At 18 months
Time to first acute ILD exacerbation
Time frame: At 18 months