Longitudinal observational study investigating outcome measures for clinical trials in inclusion body myositis

Abstract

ObjectiveTo describe decline in muscle strength and physical function in patients with sporadic inclusion body myositis (IBM).MethodsManual muscle testing (MMT), quantitative muscle testing (QMT) and disability scoring using the IBM Functional Rating Scale (IBMFRS) were undertaken for 181 patients for up to 7.3 years. The relationship between MMT, QMT and IBMFRS composite scores and time from onset were examined using linear mixed effects models adjusted for gender and age of disease onset. Adaptive LASSO regression analysis was used to identify muscle groups that best predicted the time elapsed from onset. Cox proportional hazards regression was used to evaluate time to use of a mobility aid.ResultsMultilevel modelling of change in percentage MMT, QMT and IBMFRS score over time yielded an average decline of 3.7% (95% CI 3.1% to 4.3%), 3.8% (95% CI 2.7% to 4.9%) and 6.3% (95% CI 5.5% to 7.2%) per year, respectively. The decline, however, was not linear, with steeper decline in the initial years. Older age of onset was associated with a more rapid IBMFRS decline (p=0.007), but did not influence the rate of MMT/QMT decline. Combination of selected muscle groups allowed for generation of single measures of patient progress (MMT and QMT factors). Median (IQR) time to using a mobility aid was 5.4 (3.6–9.2) years, significantly affected by greater age of onset (HR 1.06, 95% CI 1.04 to 1.09, p<0.001).ConclusionThis prospective observational study represents the largest IBM cohort to date. Measures of patient progress evaluated in this study accurately predict disease progression in a reliable and useful way to be used in trial design.

A cross‐sectional study of memory and executive functions in patients with sporadic inclusion body myositis

“…Participants were recruited from the longitudinal study “Natural History of Inclusion Body Myositis,” for which the inclusion criteria were a diagnosis of IBM made by a neuromuscular expert and the fulfillment of established IBM classification criteria 8 . Invitations for an optional neuropsychological assessment at the University College London Centre for Neuromuscular Diseases were issued sequentially when patients attended clinic appointments and the neuropsychometrist was available.…”

Measuring change in inclusion body myositis: clinical assessments versus imaging

“…Most frequently, strength testing across several muscles group has been assessed using manual muscle testing (MMT) (6,10,(13)(14)(15)(16)(17)(18), hand-held dynamometry (HHD) (9,(14)(15)(16)(17)(19)(20)(21), and/or quantitative muscle testing (QMT) using a fixed system with force transducers and load cells (6,10,11,(22)(23)(24). While the exact muscle groups and methods of strength testing differ across studies, knee extensors and finger flexors, including pinch and hand grip, were most frequently assessed (6,(9)(10)(11)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24). In longitudinal studies, overall grouped strength declines ranged between 2-8% per year, whereas strength in individual muscle groups (i.e.…”

“…While there are several types of COA including patient-reported, observer-reported, clinician-reported, and performance based COA, the United States Food and Drug Administration (FDA) focuses COA on measures that report how a patient feels, functions, or survives (8). Natural history studies in sIBM provide a framework for counselling patients within a multidisciplinary clinic about average expectations for disease progression, differentiating disease-related and unrelated signs and symptoms, and aid in identification of outlier performance or trajectories (9,10). Similarly, standard use of COA within a clinical environment can guide patient counselling, as key factors impacting a particular skill can be identified, and equipment prescription, as time to loss of a particular skill can be anticipated (11).…”

Diagnostic and prognostic value of anti-cN1A antibodies in inclusion body myositis

“…It is often reported as the most common acquired muscle disease in individuals aged above 50 (2,3). The classic pattern of weakness described is characterised by involvement of the long finger flexors, quadriceps and foot dorsiflexors (4)(5)(6). Patients can often develop dysphagia which can have a significant impact on prognosis.…”