Rationale Mechanistic target of rapamycin inhibitors reduce loss of lung function in lymphangioleiomyomatosis (LAM), although their benefit varies between individuals. We examined lung function response and side effects to rapamycin in a national cohort.
Methods Subjects were receiving rapamycin for progressive lung disease. Clinical evaluation, detailed phenotyping, serial lung function, rapamycin and safety monitoring were performed according to a clinical protocol. Lung function change, measured as FEV1 slope (ΔFEV1), was reported for those treated for 1 year or longer.
Results Rapamycin was associated with improved ΔFEV1 in 21 individuals where pretreatment data were available (p<0.0001). In 47 treated for a mean duration of 35.8 months, mean ΔFEV1 was +11 (SD 75) mL/year, although it varied from +254 to −148 mL/year. The quartile with the highest positive ΔFEV1 had greater pretreatment FEV1 (p=0.02) and shorter disease durations (p=0.02) than the lowest quartile. Serum rapamycin level was positively associated with side effects (p=0.02) but not ΔFEV1 over 1 year. Within the first month of therapy, apthous ulcers, nausea and diarrhoea were associated with higher rapamycin levels. Acne, oedema and menstrual irregularities tended to increase over the first year of therapy. At the end of observation, the prevalence of side effects was 5% or less.
Conclusions Rapamycin reduces lung function loss in LAM, although in some, ΔFEV1 continues to fall at an accelerated rate. Poor response to rapamycin was associated with lower pretreatment lung function and longer disease duration but not serum level. Early intervention with low-dose rapamycin may preserve lung function and reduce side effects.
- rare lung diseases
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Contributors SRJ conceived the study. SRJ and SF saw all participants. JB, SF, SM and SRJ recorded and analysed the data. All authors contributed to the final manuscript.
Competing interests None declared.
Patient consent Detail has been removed from this case description/these case descriptions to ensure anonymity. The editors and reviewers have seen the detailed information available and are satisfied that the information backs up the case the authors are making.
Ethics approval East Midlands Research Ethics Committee (13/EM/0264).
Provenance and peer review Not commissioned; externally peer reviewed.
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