Utility of N-of-1 trials in the Assessment and Management of Patients with Statin-related Myopathy

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: SUN 723-739-Lipids: Therapeutics & Case Reports
Sunday, June 16, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board SUN-726
Alaa Monjed*1, Jeffrey L Mahon1, Gy Zou2, Charlotte Mcdonald1, Robert Alexander Hegele2 and Tisha Joy3
1University of Western Ontario, London, ON, Canada, 2Robarts Research Institute, London, ON, Canada, 3St. Joseph's Health Centre, London, ON, Canada
Context:Statin-related myopathy occurs in at least 10% of individuals prescribed statins.  Unfortunately, no specific objective test or biomarker separates myalgias secondary to statins from myalgias due to other causes, sometimes resulting in premature statin withdrawal. Aim:To assess the potential value of N-of-1 trials (single-patient, double blind, randomized, multiple crossover comparisons) for evaluating reproducibility of myalgias from statins in patients with a history of statin-related myopathy.Methods:Ten patients developing myalgias within 3 weeks of statin initiation but without significant creatine kinase (CK) elevation (CK > 3 times upper limit of normal) were enrolled. The statin previously associated with myalgias formed the active arm; matching placebos were compounded into identical capsules.  Each active and placebo drug was given in 3 week periods in pairs, separated by a 3 week washout. The order within pairs was randomly determined.  A complete N-of-1 trial was 3 active and 3 placebo treatment periods and lasted 33 weeks.Outcomes and Analysis:Myalgias were documented weekly during each 3-week treatment period by Visual Analogue Scale (VAS) and Brief Pain Inventory (BPI).  Pain Interference Score (PIS) and Pain Severity Score (PSS) were derived from BPI.  Higher scores indicate worse pain-related outcomes. Main outcome was myalgias by VAS; secondary outcomes were PSS and PIS. Point estimate and 95% confidence intervals (95% CI) were determined on the difference in mean symptom scores within treatment pairs.  An N-of-1 trial was considered positive if the point estimate was higher during statin therapy in completed pairs with a p value < 0.05 by a paired t test.Results:Of 10 patients enrolled, 2 withdrew prior to starting; 7 completed 3 pairs; 1 finished 2 pairs. In all 8 N-of-1 trials, no significant differences in VAS, PIS, and PSS between statin and placebo periods were shown.  For differences in myalgias by VAS, point estimates ranged from -8.11 to +21.00 with 95% CIs crossing zero in all cases.  Upon review, 1 patient no longer required statin therapy and 5 of the remaining 7 (71%) chose to resume open-label statin.  All 5 are still on statin at least 6 months after study conclusion.Conclusions: In these patients, N-of-1 trials provided objective data that statins did not cause their prior myalgias.  N-of-1 trials may be useful in select patients who warrant statin therapy but had myalgias previously during open treatment.

Disclosure: TJ: Medical Advisory Board Member, Sanofi, Speaker Bureau Member, Novo Nordisk, Speaker Bureau Member, Merck & Co.. Nothing to Disclose: AM, JLM, GZ, CM, RAH

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm