MADRID – Arimoclomol showed promise as a treatment for the most common type of inflammatory myopathy in adults over age 50 in a 1-year, phase IIa, "proof-of-concept" study.
Not only was the novel oral agent "well tolerated," which was the study’s main objective to assess, but it also showed early signs that it could be effective in the treatment of patients with sporadic inclusion body myositis (IBM). Indeed, there was a trend toward slower deterioration in physical function, muscle strength, and right-hand grip muscle strength for arimoclomol when compared against placebo at 8 months’ follow-up.
"IBM is an enigmatic disease," study investigator Dr. Pedro Machado said at the recent annual European Congress of Rheumatology. "IBM muscle tissue displays [both] inflammatory and degenerative features."
Dr. Machado, a senior clinical research associate at the MRC Centre for Neuromuscular Diseases at University College London (UCL), explained that arimoclomol targets the heat shock response, amplifying the expression of heat shock protein. As such, it potentially targets both the degenerative and inflammatory components of the disease. "Previous studies have only involved agents directly purely at the inflammatory component of IBM pathology, and all were ineffective," the researcher observed.
For the double-blind study, teams based at UCL and the University of Kansas, Kansas City, collaborated to recruit 17 men and 7 women (mean age, 67 years) who had had IBM for an average of about 8 years. These patients were randomized in a 2:1 ratio to receive active therapy with arimoclomol 100 mg three times daily or matching placebo for 4 months, with follow-up lasting for 12 months (Ann. Rheum. Dis. 2013;72:164).
The investigators assessed patients for the development of adverse events, physical function using the IBM functional rating scale (IBMFRS), and muscle strength via manual muscle testing and maximum voluntary isometric contraction testing (MVICT) at 4, 8, and 12 months. They also measured the patients’ fat-free mass percentage with dual-energy x-ray absorptiometry at 4 and 12 months, and took muscle biopsies to assess the levels of heat shock protein 70 in muscle tissue before and after 4 months of treatment.
Fourteen of the 16 patients randomized to arimoclomol completed 4 months of treatment; 1 patient returned for final assessment at 12 months’ follow-up. All eight placebo patients completed 12 months of follow-up.
"The drug was very safe and well tolerated. Compliance was, on average, 99%, and we also performed ophthalmological assessment, and there were no ophthalmological problems," Dr. Machado said.
The most common adverse events were gastrointestinal problems, infections, and falls, although there was no difference between the arimoclomol and placebo groups in terms of the frequency, type, or severity of these or other adverse events. "We have to remind ourselves that this is an elderly population," Dr. Machado said, noting that the infections seen all responded to standard antibiotic therapy.
"There was one serious adverse event," he conceded. This was a case of hypertension requiring prolonged hospitalization in a patient given arimoclomol. "There were also two cases of hyponatremia in the arimoclomol group, but this was mild, transient, and asymptomatic, and it resolved without treatment."
At 4, 8, and 12 months after baseline, scores on the IBMFRS in the arimoclomol versus the placebo arm changed by a respective –0.34 vs. –0.88 (P = .239), –0.68 vs. –2.50 (P = .055), and –2.03 vs. –3.50 (P = .538). These data suggest that less deterioration in physical function occurred with arimoclomol than with placebo, Dr. Machado said.
Muscle strength appeared to improve with active treatment, as did right-hand grip strength based on MVICT results at 8 months that approached significance (1.26 vs. –0.54; P = .064).
"A trend towards a slower deterioration was observed in the arimoclomol group for the IBMFRS, for the [muscle] strength score, and for the quantitative muscle assessment only for the right-hand grip assessment at 8 months," Dr. Machado said.
He concluded: "This shows a preliminary signal for potential therapeutic benefit in patients with IBM, and therefore we believe that these data support further research of arimoclomol in inclusion body myositis."
The study was funded by Arthritis Research UK, a University of Kansas Neurology Ziegler Grant, and a University of Kansas General Clinical Research Center CReFF Grant. Dr. Machado had no disclosures.