Sarcoidosis incidence after mTOR inhibitor treatment

Semin Arthritis Rheum. 2022 Dec:57:152102. doi: 10.1016/j.semarthrit.2022.152102. Epub 2022 Sep 25.

Abstract

Objective: Mechanistic target of rapamycin (mTOR) inhibitors are effective in animal models of granulomatous disease, but their benefit in sarcoidosis patients is unknown. We evaluated the incidence of sarcoidosis in patients treated with mTOR inhibitors versus calcineurin inhibitors.

Methods: This was a cohort study using the Optum Clinformatics® Data Mart (CDM) Database (2003-2019), IBM® MarketScan® Research Database (2006-2016), and Danish health and administrative registries (1996-2018). Patients aged ≥18 years with ≥1 year continuous enrollment before and after kidney, liver, heart, or lung transplant treated with an mTOR inhibitor or calcineurin inhibitor were included. Patients diagnosed with sarcoidosis before, or up to 90 days after, transplant were excluded. The incidence of sarcoidosis by treatment group was calculated.

Results: In the Optum CDM/IBM MarketScan cohort, 1,898 patients were treated with an mTOR inhibitor (mean age 49 years; 34% female) and 9,894 patients were treated with a calcineurin inhibitor (mean age 50 years; 37% female). The mean follow-up in the mTOR inhibitor group was 1.1 years, with no incident sarcoidosis diagnosed. In the calcineurin inhibitor group, the mean follow-up was 2.2 years, with 12 incident sarcoidosis cases diagnosed. In the Danish cohort, 230 patients were treated with an mTOR inhibitor (mean age 49; 45% female), with no incident sarcoidosis diagnosed. There were 3,411 patients treated with a calcineurin inhibitor (mean age 45; 40% female), with 10 incident cases of sarcoidosis diagnosed.

Conclusions: This study indicates a potential protective effect of mTOR inhibitor treatment compared with calcineurin inhibitor treatment against the development of sarcoidosis.

Keywords: Granuloma; Sarcoidosis; mTOR.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Calcineurin Inhibitors / adverse effects
  • Cohort Studies
  • Female
  • Humans
  • Immunosuppressive Agents* / adverse effects
  • Immunosuppressive Agents* / therapeutic use
  • Incidence
  • Kidney Transplantation*
  • MTOR Inhibitors* / therapeutic use
  • Male
  • Sarcoidosis* / chemically induced
  • Sarcoidosis* / epidemiology
  • TOR Serine-Threonine Kinases

Substances

  • Calcineurin Inhibitors
  • Immunosuppressive Agents
  • MTOR Inhibitors
  • MTOR protein, human
  • TOR Serine-Threonine Kinases