Efficacy of sirolimus for treatment of autoimmune lymphoproliferative syndrome: a systematic review of open label clinical studies

Background Although autoimmune lymphoproliferative syndrome (ALPS) is an unusual and fatal disorder to which no absolute cure stands, there also remains substantial diversity with majority of subjects exhibiting only slight associated morbidities. Several pre-clinical and clinical evidence in the past have reported sirolimus to be an effective therapeutic option for patients with autoimmune cytopenias who are often resistant and intolerant to standard treatment. Thus, this systematic review aimed to assess the efficacy of sirolimus for treatment of autoimmune cytopenias, particularly ALPS. Methods This systematic review was performed in adherence to the PRISMA 2009 checklist for preferred reporting items for systematic reviews and meta-analyses. Data search was carried out in PubMed and clinicaltrials.gov from inception to 10 June 2020. Newcastle-Ottawa Scale (NOS) was used for assessing study quality. Results A total of three open label clinical studies comprising 94 patients with ALPS (53.20% males and 46.80% females) were included. The majority of patients with ALPS demonstrated rapid, complete, and durable responses with recovery of their primary disease manifestations. Stabilization of lymphoproliferation and a decrease in abnormal DNT cells was also noted. Moreover, sirolimus was found to be safe with few side effects that could be tolerated well. Conclusion This systematic review corroborated on available evidence which jointly emphasizes that complete responses could be seen in estimates of 50% or more patients with ALPS and although, there is a need of larger trials, the findings do support the chronic use of sirolimus for treatment of ALPS.

Automated summary

This systematic review evaluated the efficacy of sirolimus for treatment of autoimmune cytopenias, particularly ALPS. The majority of ALPS patients showed rapid, complete, and durable responses with recovery of their primary disease manifestations, as well as stabilization of lymphoproliferation and a decrease in abnormal DNT cells. Sirolimus was found to be safe with few side effects that could be tolerated well, supporting its chronic use for the treatment of ALPS.