Table 3.
Results from the off-label use of RTX in SSc
| Studies | Study design | Number of patients | Drug regimen | Results |
|---|---|---|---|---|
| Lafyatis et al71 | Open-label Observational |
15 dcSSc | RTX 1 g 2 weeks apart | Primary outcome: Change in mRSS at 6 months: no change Secondary outcomes: PFTs: stable Organ involvement: stable B cell infiltrates: depleted (vs baseline) Autoantibodies: modest changes |
| Bosello et al72 | Open-label | 9 SSc | RTX 1 g 2 weeks apart | Follow-up up to 36 months (skin biopsy at baseline and during the follow-up): After 6 months; skin score, disease activity index and disease severity index: decreased IL-6: reduced Serum B cells: reduced in seven patients B cells at baseline in three patients |
| Daoussis et al73 | Open-label | 8 dcSSc with ILD | RTX 375 mg/m2/week for 4 weeks | Long-term (2 years) safety and efficacy: Lung involvement (PFTs and HRCT): improved Skin involvement (mRSS and myofibroblast): improved |
| Smith et al74 | Open-label | 8 dcSSc | RTX 1 g 2 weeks apart | 24-week follow-up: Peripheral CD19+: reduced Skin sclerosis score: reduced Biopsies (dermal hyalinized collagen content and dermal myofibroblast numbers): change |
| Smith et al75 | Open-label | 8 dcSSc | RTX 1 g 2 weeks apart at baseline and after 6 months | 2-year follow-up: mRSS: decreased DAS: decreased Internal organ involvement: stable B cell depletion Biopsies (hyalinized collagen score): change |
| Moazedi-Fuerst et al76 | Open-label | 5 SSc with ILD nonresponders to CYC | RTX 500 mg 2 weeks apart every 3 months for 1 year | mRSS: decreased DLCO and FVC: increased Lung fibrosis (three patients): decreased Digital ulcerations: healed Severity of Raynaud’s phenomenon and vascular pain: decreased Number of capillary bleeds and megacapillaries: decreased B-lymphocyte count decreased Serum immunoglobulins, autoantibody titers or CRP levels: no change |
| Giuggioli et al77 | Open-label | 10 SSc | One or more cycles of RTX 375 mg/m2/week for 4 weeks | Follow-up at 6 months and at last follow-up (up to 72 months): mRSS: decreased at 6 months Other cutaneous manifestations (hypermelanosis, pruritus, calcinosis): improved Arthritis: improved ILD: stable in 6 and worsened in 2 Pro-inflammatory cytokines: a more or less pronounced reduction after the first RTX cycle |
| Daoussis et al78 | Randomized | 14 SSc | 8: RTX 375 m2 weekly for 4 weeks at baseline and at 24 weeks plus standard therapy 6: standard treatment alone |
1-year follow-up: FVC, DLCO and skin involvement: increased |
| Jordan et al81 | Registry Case–control |
88 SSc | 63: RTX 1 g 2 weeks apart 25: controls |
Primary end point: mRSS: reduced better in RTX Secondary end points: FVC: no further decline Safety measures: good |
| Bosello et al82 | Open-label | 29 dcSSc with or without ILD | RTX 1 g 2 weeks apart (more courses when needed) | Follow-up up to 68.9 months: Skin score, activity and severity indices improved significantly after 12 months and at final follow-up compared to baseline FVC and TLC: increased DLCO: stable HRCT: stable in 80% of patients |
| Daoussis et al83 | Multicenter Open-label |
51 SSc with ILD | 33: RTX 375 m2 weekly for 4 weeks 18: conventional therapy |
Median follow-up 4 years (up to 7 years): FVC: increased at 2-year follow-up, results confirmed at 7 years mRSS: outcome favorable to RTX at all times |
Abbreviations: CRP, C-reactive protein; CYC, cyclophosphamide; DAS, Disease Activity Score; dcSSc, diffuse cutaneous SSc; DLCO, carbon monoxide diffusing capacity; FVC, forced vital capacity; HRCT, high-resolution computed tomography; IL-6, interleukin-6; ILD, interstitial lung disease; mRSS, Rodnan skin thickness score; PFTs, pulmonary function tests; RTX, rituximab; SSc, systemic sclerosis; TLC, total lung capacity.