Immunosuppressive Therapy After Autologous Hematopoietic Stem Cell Transplantation in Systemic Sclerosis Patients—High Efficacy of Rituximab

Abstract

BackgroundSystemic sclerosis (SSc) patients often need immunosuppressive medication (IS) for disease control. If SSc is progressive despite IS, autologous hematopoietic stem cell transplantation (aHSCT) is a treatment option for selected SSc patients. aHSCT is effective with good available evidence, but not all patients achieve a treatment-free remission after aHSCT. Thus far, data about the need of IS after aHSCT in SSc is not published. The aim of this study was to investigate the use of IS after aHSCT, its efficacy, and the occurrence of severe adverse events (SAEs).MethodsTwenty-seven patients with SSc who had undergone aHSCT were included in this single-center retrospective cohort study. Clinical data, including IS, SAEs, and lung function data, were collected.ResultsSixteen of 27 (59.3%) patients received IS after aHSCT. Methotrexate, rituximab, mycophenolate, cyclophosphamide, and hydroxychloroquine were most commonly used. The main reason for starting IS was SSc progress. Nine patients received rituximab after aHSCT and showed an improvement in modified Rodnan skin score and a stabilization of lung function 2 years after rituximab. SAEs in patients with IS after aHSCT (50.0%) were not more common than in patients without IS (54.6%). SAEs were mostly due to SSc progress, secondary autoimmune diseases, or infections. Two deaths after aHSCT were transplantation related and three during long-term follow-up due to pulmonary arterial hypertension.ConclusionDisease progression and secondary autoimmune diseases may necessitate IS after aHSCT in SSc. Rituximab seems to be an efficacious treatment option in this setting. Long-term data on the safety of aHSCT is reassuring.

Autologous Haematopoietic Stem Cell Transplantation and Systemic Sclerosis: Focus on Interstitial Lung Disease

“…In fact, longer-term follow-up of pulmonary function and alterations shows that the effects of AHSCT on the evolution of ILD tend to decrease over-time and eventually disappear in some patients, returning to the pre-transplant conditions two years after AHSCT. For this group of patients, Rituximab, an anti-cd20 biologic agent, showed a promising profile of safety and efficacy, offering the opportunity to avoid ILD recurrence or worsening after AHSCT [ 45 ]. This directly raises the question whether future trials should focus on the stabilization of pulmonary function improvement after AHSCT and to identify SSc patients at risk of long-term ILD progression or re-activation.…”

Case report: A successful second autologous hematopoietic stem cell transplantation in refractory systemic sclerosis, with positive effect on skin involvement, pulmonary function and microcirculation

“…In addition, targeted B-cell therapy with rituximab might be considered. Rituximab represents a promising strategy for skin and lung fibrosis in SSc but long term data is missing and in fact, to date, this is an experimental treatment also ( 11 , 14 , 16 ). Furthermore, treatment with Nintedanib was discussed but declined as this has not shown effect on skin involvement.…”

Hematopoietic Cell Transplantation for Systemic Sclerosis—A Review

“…Findings that suggest this include changes to in vitro IL-10 production with CpG-stimulated purified patient total B cells [ 59 ] and by inhibition of IFNg and TNFa production with in vitro stimulated CD4 T cells [ 58 ]. However, if Bregs play a significant role, it is difficult to explain why rituximab appears effective in patients who relapsed after HCT [ 60 , 61 ], with rituximab theoretically expected to eliminate the few Bregs that the relapsing patients may still possess. One such explanation could be that rituximab does not in practice deplete all B cell populations, as has been seen with marginal zone B cells [ 62 ].…”

“…For example, in the SCOT trial, 9% of HCT recipients vs. 44% of controls started an immunomodulatory drug within the first 4.5 years [ 23 ], with the difference remaining significant at 6–11 years [ 95 ]. Aside from the randomized trials, disease progression varies among longitudinal studies but has been reported to occur in 11% to almost 31% [ 44 , 45 , 60 , 145 ] of patients at 4.4 years, 10.5% to 24% at 8 years [ 107 , 117 ], and 42% at 11 years [ 75 ] after HCT. While the reasons for this heterogeneity are unclear, it is likely due to differences in patient selection, follow-up duration, and the definition of relapse used.…”

“…In RA patients who had relapsed after autoHCT, rituximab resulted in clinical improvements similar to their initial responses to autoHCT in 80% of patients [ 61 ]. Subsequently, a single-center analysis of nine HCT recipients who received rituximab for SSc relapse after HCT (n = 6) or for a new autoimmune disease (n = 3) showed improved mRSS (compared to no improvement in seven patients who received no immunomodulatory therapy after relapse) and stabilization of lung function [ 60 ]. Alternatively, a second autoHCT was successful for treating SSc relapse in one reported case [ 146 ].…”