Treatment for inclusion body myositis

Background Inclusion body myositis (IBM) is a late-onset inflammatory muscle disease (myopathy) associated with progressive proximal and distal limb muscle atrophy and weakness. Treatment options have attempted to target inflammatory and atrophic features of this condition (for example with immunosuppressive and immunomodulating drugs, anabolic steroids, and antioxidant treatments), although as yet there is no known effective treatment for reversing or minimising the progression of inclusion body myositis. In this review we have considered the benefits, adverse effects, and costs of treatment in targeting cardinal effects of the condition, namely muscle atrophy, weakness, and functional impairment. Objectives To assess the effects of treatment for IBM. Search methods On 7 October 2014 we search ed the Cochrane Neuromuscular Disease Group Specialized Register, the Cochrane Central Register for Controlled Trials (CENTRAL), MEDLINE, and EMBASE. Additionally in November 2014 we searched clinical trials registries for ongoing or completed but unpublished trials. Selection criteria We considered randomised or quasi-randomised trials, including cross-over trials, of treatment for IBM in adults compared to placebo or any other treatment for inclusion in the review. We specifically excluded people with familial IBM and hereditary inclusion body myopathy, but we included people who had connective tissue and autoimmune diseases associated with IBM, which may or may not be identified in trials. We did not include studies of exercise therapy or dysphagia management, which are topics of other Cochrane systematic reviews. Data collection and analysis We used standard Cochrane methodological procedures. Main results 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. Authors\u27 conclusions 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

Pharmacological treatments for Friedreich ataxia

Background: Friedreich ataxia is a rare inherited autosomal recessive neurological disorder, characterised initially by unsteadiness in standing and walking, slowly progressing to wheelchair dependency usually in the late teens or early twenties. It is associated with slurred speech, scoliosis, and pes cavus. Heart abnormalities cause premature death in 60% of people with the disorder. There is no easily defined clinical or biochemical marker and no known treatment. This is the second update of a review first published in 2009 and previously updated in 2012. Objectives: To assess the effects of pharmacological treatments for Friedreich ataxia. Search methods: On 29 February 2016 we searched The Cochrane Neuromuscular Specialised Register, CENTRAL, MEDLINE, EMBASE and CINAHL Plus. On 7 March 2016 we searched ORPHANET and TRIP. We also checked clinical trials registers for ongoing studies. Selection criteria: We considered randomised controlled trials (RCTs) or quasi-RCTs of pharmacological treatments (including vitamins) in people with genetically-confirmed Friedreich ataxia. The primary outcome was change in a validated Friedreich ataxia neurological score after 12 months. Secondary outcomes were changes in cardiac status as measured by magnetic resonance imaging or echocardiography, quality of life, mild and serious adverse events, and survival. We excluded trials of duration shorter than 12 months. Data collection and analysis: Three review authors selected trials and two review authors extracted data. We obtained missing data from the two RCTs that met our inclusion criteria. We collected adverse event data from included studies. We used standard methodological procedures expected by Cochrane. Main results: We identified more than 12 studies that used antioxidants in the treatment of Friedreich ataxia, but only two small RCTs, with a combined total of 72 participants, both fulfilled the selection criteria for this review and published results. One of these trials compared idebenone with placebo, the other compared high-dose versus low-dose coenzyme Q10 and vitamin E (the trialists considered the low-dose medication to be the placebo). We identified two other completed RCTs, which remain unpublished; the interventions in these trials were pioglitazone (40 participants) and idebenone (232 participants). Other RCTs were of insufficient duration for inclusion. In the included studies, the primary outcome specified for the review, change in a validated Friedreich ataxia rating score, was measured using the International Co-operative Ataxia Rating Scale (ICARS). The results did not reveal any significant difference between the antioxidant-treated and the placebo groups (mean difference 0.79 points, 95% confidence interval -1.97 to 3.55 points; low-quality evidence). The published included studies did not assess the first secondary outcome, change in cardiac status as measured by magnetic resonance imaging. Both studies reported changes in cardiac measurements assessed by echocardiogram. The ejection fraction was not measured in the larger of the included studies (44 participants). In the smaller study (28 participants), it was normal at baseline and did not change with treatment. End-diastolic interventricular septal thickness showed a small decrease in the smaller of the two included studies. In the larger included study, there was no decrease, showing significant heterogeneity in the study results; our overall assessment of the quality of evidence for this outcome was very low. Left ventricular mass (LVM) was only available for the smaller RCT, which showed a significant decrease. The relevance of this change is unclear and the quality of evidence low. There were no deaths related to the treatment with antioxidants. We considered the published included studies at low risk of bias in six of seven domains assessed. One unpublished included RCT, a year-long study using idebenone (232 participants), published an interim report in May 2010 stating that the study reached neither its primary endpoint, which was change in the ICARS score, nor a key cardiological secondary endpoint, but data were not available for verification and analysis. Authors' conclusions: Low-quality evidence from two small, published, randomised controlled trials neither support nor refute an effect from antioxidants (idebenone, or a combination of coenzyme Q10 and vitamin E) on the neurological status of people with Friedreich ataxia, measured with a validated neurological rating scale. A large unpublished study of idebenone that reportedly failed to meet neurological or key cardiological endpoints, and a trial of pioglitazone remain unpublished, but on publication will very likely influence quality assessments and conclusions. A single study of idebenone provided low-quality evidence for a decrease in LVM, which is of uncertain clinical significance but of potential importance that needs to be clarified. According to low-quality evidence, serious and non-serious adverse events were rare in both antioxidant and placebo groups. No non-antioxidant agents have been investigated in RCTs of 12 months' duration.SCOPUS: re.jinfo:eu-repo/semantics/publishe

Immunosuppressive and immunomodulatory therapies for idiopathic inflammatory myopathies

Objectives: This is a protocol for a Cochrane Review (intervention). The objectives are as follows:. This protocol is for two separate reviews to assess the effects (benefits and harms) of immunosuppressant and immunomodulatory treatments for the idiopathic inflammatory myopathies. Targeted treatments To assess the effects (benefits and harms) of targeted immunosuppressant and immunomodulatory treatments for the idiopathic inflammatory myopathies: dermatomyositis (DM, including juvenile dermatomyositis, jDM), immune mediated necrotising myopathy (IMNM), anti-synthetase syndrome (ASS), overlap-myositis (OM) and polymyositis (PM). We will also include cancer-related myositis and amyopathic dermatomyositis. Non-targeted treatments To assess the effects (benefits and harms) of non-targeted immunosuppressant and immunomodulatory treatments for the idiopathic inflammatory myopathies: dermatomyositis (DM, including juvenile dermatomyositis, jDM), immune mediated necrotising myopathy (IMNM), anti-synthetase syndrome (ASS), overlap-myositis (OM) and polymyositis (PM). We will also include cancer-related myositis and amyopathic dermatomyositis

Endoscopic and Open Release Similarly Safe for the Treatment of Carpal Tunnel Syndrome. A Systematic Review and Meta-Analysis.

BACKGROUND The Endoscopic Release of Carpal Tunnel Syndrome (ECTR) is a minimal invasive approach for the treatment of Carpal Tunnel Syndrome. There is scepticism regarding the safety of this technique, based on the assumption that this is a rather "blind" procedure and on the high number of severe complications that have been reported in the literature. PURPOSE To evaluate whether there is evidence supporting a higher risk after ECTR in comparison to the conventional open release. METHODS We searched MEDLINE (January 1966 to November 2013), EMBASE (January 1980 to November 2013), the Cochrane Neuromuscular Disease Group Specialized Register (November 2013) and CENTRAL (2013, issue 11 in The Cochrane Library). We hand-searched reference lists of included studies. We included all randomized or quasi-randomized controlled trials (e.g. study using alternation, date of birth, or case record number) that compare any ECTR with any OCTR technique. Safety was assessed by the incidence of major, minor and total number of complications, recurrences, and re-operations.The total time needed before return to work or to return to daily activities was also assessed. We synthesized data using a random-effects meta-analysis in STATA. We conducted a sensitivity analysis for rare events using binomial likelihood. We judged the conclusiveness of meta-analysis calculating the conditional power of meta-analysis. CONCLUSIONS ECTR is associated with less time off work or with daily activities. The assessment of major complications, reoperations and recurrence of symptoms does not favor either of the interventions. There is an uncertain advantage of ECTR with respect to total minor complications (more transient paresthesia but fewer skin-related complications). Future studies are unlikely to alter these findings because of the rarity of the outcome. The effect of a learning curve might be responsible for reduced recurrences and reoperations with ECTR in studies that are more recent, although formal statistical analysis failed to provide evidence for such an association. LEVEL OF EVIDENCE I

Immunoglobulin for multifocal motor neuropathy

Background: Multifocal motor neuropathy (MMN) is a rare, probably immune-mediated disorder characterised by slowly progressive, asymmetric, distal weakness of one or more limbs with no objective loss of sensation. It may cause prolonged periods of disability. Treatment options for MMN are few. People with MMN do not usually respond to steroids or plasma exchange. Uncontrolled studies have suggested a beneficial effect of intravenous immunoglobulin (IVIg). This is an update of a Cochrane Review first published in 2005, with an amendment in 2007. We updated the review to incorporate new evidence. Objectives: To assess the efficacy and safety of intravenous and subcutaneous immunoglobulin in people with MMN. Search methods: We searched the following databases on 20 April 2021: the Cochrane Neuromuscular Specialised Register, CENTRAL, MEDLINE, Embase, ClinicalTrials.gov, and WHO ICTRP for randomised controlled trials (RCTs) and quasi-RCTs, and checked the reference lists of included studies. Selection criteria: We considered RCTs and quasi-RCTs examining the effects of any dose of IVIg and subcutaneous immunoglobulin (SCIg) in people with definite or probable MMN for inclusion in the review. Eligible studies had to have measured at least one of the following outcomes: disability, muscle strength, or electrophysiological conduction block. We used studies that reported the frequency of adverse effects to assess safety. Data collection and analysis: Two review authors independently reviewed the literature searches to identify potentially relevant trials, assessed risk of bias of included studies, and extracted data. We followed standard Cochrane methodology. Main results: Six cross-over RCTs including a total of 90 participants were suitable for inclusion in the review. Five RCTs compared IVIg to placebo, and one compared IVIg to SCIg. Four of the trials comparing IVIg versus placebo involved IVIg-naive participants (induction treatment). In the other two trials, participants were known IVIg responders receiving maintencance IVIg at baseline and were then randomised to maintenance treatment with IVIg or placebo in one trial, and IVIg or SCIg in the other. Risk of bias was variable in the included studies, with three studies at high risk of bias in at least one risk of bias domain. IVIg versus placebo (induction treatment): three RCTs including IVIg-naive participants reported a disability measure. Disability improved in seven out of 18 (39%) participants after IVIg treatment and in two out of 18 (11%) participants after placebo (risk ratio (RR) 3.00, 95% confidence interval (CI) 0.89 to 10.12; 3 RCTs, 18 participants; low-certainty evidence). The proportion of participants with an improvement in disability at 12 months was not reported. Strength improved in 21 out of 27 (78%) IVIg-naive participants treated with IVIg and one out of 27 (4%) participants who received placebo (RR 11.00, 95% CI 2.86 to 42.25; 3 RCTs, 27 participants; low-certainty evidence). IVIg treatment may increase the proportion of people with resolution of at least one conduction block; however, the results were also consistent with no effect (RR 7.00, 95% CI 0.95 to 51.70; 4 RCTs, 28 participants; low-certainty evidence). IVIg versus placebo (maintenance treatment): a trial that included participants on maintenance IVIg treatment reported an increase in disability in 17 out of 42 (40%) people switching to placebo and seven out of 42 (17%) remaining on IVIg (RR 2.43, 95% CI 1.13 to 5.24; 1 RCT, 42 participants; moderate-certainty evidence) and a decrease in grip strength in 20 out of 42 (48%) participants after a switch to placebo treatment compared to four out of 42 (10%) remaining on IVIg (RR 0.20, 95% CI 0.07 to 0.54; 1 RCT, 42 participants; moderate-certainty evidence). Adverse events, IVIg versus placebo (induction or maintenance): four trials comparing IVIg and placebo reported adverse events, of which data from two studies could be meta-analysed. Transient side effects were reported in 71% of IVIg-treated participants versus 4.8% of placebo-treated participants in these studies. The pooled RR for the development of side effects was 10.33 (95% CI 2.15 to 49.77; 2 RCTs, 21 participants; very low-certainty evidence). There was only one serious side effect (pulmonary embolism) during IVIg treatment. IVIg versus SCIg (maintenance treatment): the trial that compared continuation of IVIg maintenance versus SCIg maintenance did not measure disability. The evidence was very uncertain for muscle strength (standardised mean difference 0.08, 95% CI −0.84 to 1.00; 1 RCT, 9 participants; very low-certainty evidence). The evidence was very uncertain for the number of people with side effects attributable to treatment (RR 0.50, 95% CI 0.18 to 1.40; 1 RCT, 9 participants; very low-certainty evidence). Authors' conclusions: Low-certainty evidence from three small RCTs shows that IVIg may improve muscle strength in people with MMN, and low-certainty evidence indicates that it may improve disability; the estimate of the magnitude of improvement of disability has wide CIs and needs further studies to secure its significance. Based on moderate-certainty evidence, it is probable that most IVIg responders deteriorate in disability and muscle strength after IVIg withdrawal. SCIg might be an alternative treatment to IVIg, but the evidence is very uncertain. More research is needed to identify people in whom IVIg withdrawal is possible and to confirm efficacy of SCIg as an alternative maintenance treatment

Cumulative mean difference (MD) and 95% confidence interval (CI) for complications time to return to work or daily activities.

<p>The extended lines outside the diamond in the final meta-analytic summary shows the 95% prediction intervals. Asterisk indicates that the study has used a two-portal ECTR.</p

Cumulative odds ratios (OR) and 95% confidence interval (CI) for minor (panel a) and major (panel b) complications.

<p>The extended lines outside the diamond in the final meta-analytic summary shows the 95% prediction intervals. Asterisk indicates that the study has used a two-portal ECTR.</p

Cumulative odds ratios (OR) and 95% confidence interval (CI) for recurrence (panel a) and reoperations (panel b).

<p>The extended lines outside the diamond in the final meta-analytic summary shows the 95% prediction intervals. Asterisk indicates that the study has used a two-portal ECTR.</p