Abstract: The review included 10 trials (249 participants) using different treatment regimens. Seven of the 10 trials assessed single agents, and 3 assessed combined agents. Many of the studies did not present adequate data for the reporting of the primary outcome of the review, which was the percentage change in muscle strength score at six months. Pooled data from two trials of interferon beta-1a (n = 58) identified no important difference in normalised manual muscle strength sum scores from baseline to six months (mean difference (MD) -0.06, 95% CI -0.15 to 0.03) between IFN beta-1a and placebo (moderate-quality evidence). A single trial of methotrexate (MTX) (n = 44) provided moderate-quality evidence that MTX did not arrest or slow disease progression, based on reported percentage change in manual muscle strength sum scores at 12 months. None of the fully published trials were adequately powered to detect a treatment effect. We assessed six of the nine fully published trials as providing very low-quality evidence in relation to the primary outcome measure. Three trials (n = 78) compared intravenous immunoglobulin (combined in one trial with prednisone) to a placebo, but we were unable to perform meta-analysis because of variations in study analysis and presentation of trial data, with no access to the primary data for re-analysis. Other comparisons were also reported in single trials. An open trial of anti-T lymphocyte immunoglobulin (ATG) combined with MTX versus MTX provided very low-quality evidence in favour of the combined therapy, based on percentage change in quantitative muscle strength sum scores at 12 months (MD 12.50%, 95% CI 2.43 to 22.57). Data from trials of oxandrolone versus placebo, azathioprine (AZA) combined with MTX versus MTX, and arimoclomol versus placebo did not allow us to report either normalised or percentage change in muscle strength sum scores. A complete analysis of the effects of arimoclomol is pending data publication. Studies of simvastatin and bimagrumab (BYM338) are ongoing. All analysed trials reported adverse events. Only 1 of the 10 trials interpreted these for statistical significance. None of the trials included prespecified criteria for significant adverse events. Trials of interferon beta-1a and MTX provided moderate-quality evidence of having no effect on the progression of IBM. Overall trial design limitations including risk of bias, low numbers of participants, and short duration make it difficult to say whether or not any of the drug treatments included in this review were effective. An open trial of ATG combined with MTX versus MTX provided very low-quality evidence in favour of the combined therapy based on the percentage change data given. We were unable to draw conclusions from trials of IVIg, oxandrolone, and AZA plus MTX versus MTX. We need more randomised controlled trials that are larger, of longer duration, and that use fully validated, standardised, and responsive outcome measures.

Plain-language summary: This review included 10 trials (249 participants). One of these trials (24 participants) is completed but has not yet been published. Seven trials compared treatments with placebo (inactive treatment): three of intravenous immunoglobulin (IVIg), two of interferon beta-1a (IFN beta-1a), and one each of oxandrolone, methotrexate (MTX), and arimoclomol (not yet published). A further two trials compared MTX with combined immunosuppressive therapy (MTX with anti-T lymphocyte immunoglobulin (ATG) (an agent that destroys white blood cells) and MTX with azathioprine). In these two trials, participants and investigators knew which treatment participants were receiving, which could have biased the results. For our primary outcome, which was muscle strength, we were only able to combine the results for the two trials of IFN beta-1a therapy versus placebo. This treatment did not appear to offer a benefit in terms of muscle strength. MTX also did not stop or retard loss of muscle strength when compared to placebo. We considered the evidence from these trials to be of moderate quality because the trials were too small to rule out a possible benefit for these drugs. For the other trials, the evidence was of very low quality. Three trials compared IVIg (combined in one trial with prednisone) to a placebo, but we were unable to perform meta-analysis because the available data were not suitable. One trial of ATG combined with MTX versus MTX alone provided very low-quality evidence of an effect on muscle strength in favour of MTX plus ATG at 12 months. The other comparisons, of MTX versus placebo, oxandrolone versus placebo, azathioprine combined with MTX versus MTX, and arimoclomol versus placebo were reported in single trials that did not provide enough data for analysis of the effect on muscle strength. Due to their small size and short duration, the trials we studied were generally unable to give definitive answers as to whether the treatments tested were effective or ineffective. All of the interventions we studied had some adverse effects and are known to cause potentially serious adverse events. We need larger trials of longer duration, using robust ways of measuring the effects of treatments that are meaningful to people with IBM. Agreeing on common trial measurements will also make it easier to compare trial results and assess potential treatments. The evidence is current to October 2014.