Risk factors for stomatitis in patients with lymphangioleiomyomatosis during treatment with sirolimus: A multicenter investigator-initiated prospective study

Pharmacoepidemiol Drug Saf. 2017 Oct;26(10):1182-1189. doi: 10.1002/pds.4259. Epub 2017 Jul 28.

Abstract

Purpose: Lymphangioleiomyomatosis is a rare lung disease caused by proliferation of abnormal smooth muscle-like cells and typically occurs in premenopausal women. Sirolimus is now the first-line drug for the treatment of lymphangioleiomyomatosis. Sirolimus-induced stomatitis is the most frequent adverse event experienced during treatment. To identify risk factors, we investigated the association of stomatitis incidence with patient background data and treatment parameters, using data from the multicenter long-term sirolimus trial.

Methods: Subjects received sirolimus for 2 years at doses adjusted to maintain a trough blood level of 5 to 15 ng/mL. The incidence of stomatitis was correlated with baseline demographics, clinical characteristics, and changes in the longitudinal data. Risk factors at baseline were assessed by using univariate and multivariate analyses.

Results: The most frequent adverse event was stomatitis, with the cumulative rate reaching 88.9% by 9 months, higher than that reported in postrenal transplant patients. The repetition, the duration, and the severity of stomatitis events were variable among patients. We found that patients with low hemoglobin (Hb) (<14.5 g/dL) showed significantly higher incidence than those with high Hb (≥14.5 g/dL, P < .01). The cumulative rate for stomatitis incidence was significantly associated with a decrease in the mean corpuscular volume, while the Hb level was constant; thus, red blood cell count in patients increased during the study.

Conclusions: Baseline Hb levels and a decrease in mean corpuscular volume during treatment were correlated with the incidence of stomatitis.

Keywords: adverse events; hemoglobin; lymphangioleiomyomatosis (LAM); mTOR inhibitor; microcytosis; stomatitis.

Publication types

  • Clinical Trial
  • Multicenter Study

MeSH terms

  • Adult
  • Antibiotics, Antineoplastic / adverse effects*
  • Erythrocyte Indices / drug effects
  • Female
  • Hemoglobins / analysis
  • Humans
  • Incidence
  • Japan / epidemiology
  • Lung Neoplasms / blood
  • Lung Neoplasms / drug therapy*
  • Lymphangioleiomyomatosis / blood
  • Lymphangioleiomyomatosis / drug therapy*
  • Middle Aged
  • Multivariate Analysis
  • Prospective Studies
  • Risk Factors
  • Sirolimus / adverse effects*
  • Stomatitis / blood
  • Stomatitis / chemically induced
  • Stomatitis / epidemiology*

Substances

  • Antibiotics, Antineoplastic
  • Hemoglobins
  • Sirolimus