Long‐term strength and functional status in inclusion body myositis and identification of trajectory subgroups

Oldroyd, Alexander; Lilleker, James B; Williams, J. Powell; Chinoy, Hector; Miller, James

doi:10.1002/mus.26859

Cited by 29 publications

(31 citation statements)

References 24 publications

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“…No improvement was noted in the Short Form Health Survey physical function domain, the primary outcome measure, although a significant decrease in knee extensor strength from baseline was seen in controls (− 9.2% change, p = 0.023), not seen in the BFR exercise group (+ 0.9% change, p = 0.87). This lack of progression in the BFR exercise group may also reflect a protective effect of exercise, although the decrease in power in control does appear faster than would be expected from natural history studies [52].…”

Section: Exercisementioning

confidence: 83%

In Pursuit of an Effective Treatment: the Past, Present and Future of Clinical Trials in Inclusion Body Myositis

Snedden

Lilleker

Chinoy

2021

Curr Treat Options in Rheum

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Purpose of review No clinical trial in sporadic inclusion body myositis (IBM) thus far has shown a clear and sustained therapeutic effect. We review previous trial methodology, explore why results have not translated into clinical practice, and suggest improvements for future IBM trials. Recent findings Early trials primarily assessed immunosuppressive medications, with no significant clinical responses observed. Many of these studies had methodological issues, including small participant numbers, nonspecific diagnostic criteria, short treatment and/or assessment periods and insensitive outcome measures. Most recent IBM trials have instead focused on nonimmunosuppressive therapies, but there is mounting evidence supporting a primary autoimmune aetiology, including the discovery of immunosuppression-resistant clones of cytotoxic T cells and anti-CN-1A autoantibodies which could potentially be used to stratify patients into different cohorts. The latest trials have had mixed results. For example, bimagrumab, a myostatin blocker, did not affect the 6-min timed walk distance, whereas sirolimus, a promotor of autophagy, did. Larger studies are planned to evaluate the efficacy of sirolimus and arimoclomol. Summary Thus far, no treatment for IBM has demonstrated a definite therapeutic effect, and effective treatment options in clinical practice are lacking. Trial design and ineffective therapies are likely to have contributed to these failures. Identification of potential therapeutic targets should be followed by future studies using a stratified approach and sensitive and relevant outcome measures.

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Section: Exercisementioning

confidence: 83%

In Pursuit of an Effective Treatment: the Past, Present and Future of Clinical Trials in Inclusion Body Myositis

Snedden

Lilleker

Chinoy

2021

Curr Treat Options in Rheum

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Section: Introductionmentioning

confidence: 99%

“…Latent classes refer to patterns in a group or cohort of patients, rather than within an individual patient. This methodology has not previously been used in CIDP or MMNCB, but has been applied to serial outcome measures in other chronic conditions such as inclusion body myositis 14 and juvenile idiopathic arthritis. 15 The objective of our study was to determine, in a single-centre cohort of CIDP and MMNCB patients judged to be clinically stable by the treating clinician, the degree of random variability of commonly used outcome measures.…”

Section: Introductionmentioning

confidence: 99%

Predicting long‐term trends in inflammatory neuropathy outcome measures using latent class modelling

Keh

Selby

Jones

et al. 2022

J Peripheral Nervous Sys

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Immunoglobulin (Ig) is used to treat chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and multifocal motor neuropathy with conduction block (MMNCB). Regular infusions may be used for symptom control. Disease activity is monitored with clinical outcome measurements. We examined outcome measure variation during clinically stable periods in Ig‐treated CIDP and MMNCB patients. We explored utility of serial outcome measurement in long‐term outcome prediction. Retrospective longitudinal analysis of a single neuroscience centre's Ig‐treated CIDP and MMNCB patients, 2009‐2020, was performed. Mean and percentage change for grip strength, Rasch‐built overall disability scales (RODS) and MRC sum scores (MRC‐SS) during periods of clinical stability were compared to score‐specific minimal clinically important differences (MCID). Latent class mixed modelling (LCMM) was used to identify longitudinal trends and factors influencing long‐term outcome. We identified 85 CIDP and 23 MMNCB patients (1423 datapoints; 5635 treatment‐months). Group‐averaged outcome measures varied little over time. Intra‐individual variation exceeded MCID for RODS in 44.2% CIDP and 16.7% MMNCB datapoints, grip strength in 10.6% (CIDP) and 8.8%/27.2% (MMNCB right/left hand) and MRC‐SS in 43.5% (CIDP) and 20% (MMNCB). Multivariate LCMM identified subclinical trends towards improvement (32 patients) and deterioration (73 patients) in both cohorts. At baseline, CIDP ‘deteriorators’ were older than ‘improvers’ (66.2 vs 57 years, P = .025). No other individual factors predicted categorisation. The best model for ‘deteriorator’ identification was contiguous sub‐MCID decline in more than one outcome measure (CIDP: sensitivity 74%, specificity 59%; MMNCB: sensitivity 73%, specificity 88%). Outcome measure interpretation determines therapeutic decision‐making in Ig‐dependent neuropathy patients, but intra‐individual variation is common, often exceeding MCID. Here we show sub‐MCID contiguous changes in more than one outcome measurement are a better predictor of long‐term outcome.

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“…6,7 Of the relatively few studies that have closely examined the clinical symptoms and course of IBM, most have investigated small cohorts (mean 47 patients) with limited follow-up (mean 2•3 years). [8][9][10][11][12][13][14][15][16] Although these studies have described an overall consistent IBM phenotype, there is evidence of substantial variability both within and between studies as regards presentation, clinical progression, and accumulation of debility. While the majority of patients in these studies had an age of onset in their late fifties, a considerable number (5-20%) developed symptoms at less than 50 years of age.…”

Section: Introductionmentioning

confidence: 99%

Clinical heterogeneity based on race and sex within a large cohort of inclusion body myositis patients

Michelle

Pinal‐Fernandez

Casal-Domínguez

et al. 2022

Preprint

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Background and Objectives: Sporadic inclusion body myositis (IBM) is the most common acquired myopathy in individuals over age 50. The disorder is slowly progressive and while many therapies have been investigated, response has generally been poor. Clinical heterogeneity may influence treatment responsiveness; however, data regarding heterogeneity in IBM is limited and often conflicting. We aim to identify clinically distinct subgroups within a large IBM cohort, as well as prognostic factors for disease progression. Methods: Clinical, histologic, radiologic, and electrophysiologic data were analyzed for all patients with IBM and other forms of myositis enrolled in a longitudinal cohort from The Johns Hopkins Myositis Center from 2003-2018. Univariate, multivariate, and graphical analyses were used to identify prognostic factors in IBM patients. Results: Among the 335 IBM patients meeting inclusion criteria, 64% were male with an average age of disease onset of 58.7 years and a delay to diagnosis of 5.2 years. Initial misdiagnosis (52%) and immunosuppressant treatment (42%) were common. Less than half (43%) of muscle biopsies demonstrated all three pathologic hallmarks: endomysial inflammation, mononuclear cell invasion, and rimmed vacuoles. Black patients had significantly weaker arm abductors, hip flexors, and knee flexors compared to non-Black patients but were less likely to develop dysphagia. Female patients had stronger finger flexors and knee extensors compared to their male counterparts but were more likely to develop dysphagia. A significant number (20%) of patients had an age of onset less than 50 years. This group of younger patients was weaker at their first visit; however, this may be accounted for by a longer disease duration at first visit. Discussion: Although IBM has long been considered a disorder predominately of older, White men, female, and non-White patients comprise a significant proportion of the IBM population. Our study demonstrates that female and Black patients have distinct clinical phenotypes within the overarching IBM clinical phenotype.

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Long‐term strength and functional status in inclusion body myositis and identification of trajectory subgroups

Cited by 29 publications

References 24 publications

In Pursuit of an Effective Treatment: the Past, Present and Future of Clinical Trials in Inclusion Body Myositis

In Pursuit of an Effective Treatment: the Past, Present and Future of Clinical Trials in Inclusion Body Myositis

Predicting long‐term trends in inflammatory neuropathy outcome measures using latent class modelling

Clinical heterogeneity based on race and sex within a large cohort of inclusion body myositis patients

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