Long-term observational study of sporadic inclusion body myositis

Abstract

We describe a long-term observational study of a large cohort of patients with sporadic inclusion body myositis and propose a sporadic inclusion body myositis weakness composite index that is easy to perform during a clinic. Data collection from two groups of patients (Paris and Oxford) was completed either during a clinic visit (52%), or by extraction from previous medical records (48%). One hundred and thirty-six patients [57% males, 61 (interquartile range 55-69) years at onset] were included. At the last visit all patients had muscle weakness (proximal British Medical Research Council scale <3/5 in 48%, distal British Medical Research Council scale <3/5 in 40%, swallowing problems in 46%). During their follow-up, 75% of patients had significant walking difficulties and 37% used a wheelchair (after a median duration from onset of 14 years). The sporadic inclusion body myositis weakness composite index, which correlated with grip strength (correlation coefficient: 0.47; P < 0.001) and Rivermead Mobility Index (correlation coefficient: 0.85; P < 0.001), decreased significantly with disease duration (correlation coefficient: -0.47; P < 0.001). The risk of death was only influenced by older age at onset of first symptoms. Seventy-one (52%) patients received immunosuppressive treatments [prednisone in 91.5%, associated (in 64.8%) with other immunomodulatory drugs (intravenous immunoglobulins, methotrexate or azathioprine) for a median duration of 40.8 months]. At the last assessment, patients who had been treated were more severely affected on disability scales (Walton P = 0.007, Rivermead Mobility Index P = 0.004) and on the sporadic inclusion body myositis weakness composite index (P = 0.04). The first stage of disease progression towards handicap for walking was more rapid among patients receiving immunosuppressive treatments (hazard ratio = 2.0, P = 0.002). This study confirms that sporadic inclusion body myositis is slowly progressive but not lethal and that immunosuppressive treatments do not ameliorate its natural course, thus confirming findings from smaller studies. Furthermore, our findings suggest that immunosuppressant drug therapy could have modestly exacerbated progression of disability. The sporadic inclusion body myositis weakness composite index might be a valuable outcome measure for future clinical trials, but requires further assessment and validation.

Immune and myodegenerative pathomechanisms in inclusion body myositis

“…The clinical presentation is heterogenous and at times difficult to distinguish from other inflammatory myopathies (muscle weakness and atrophy), motor‐neuron disease (asymmetry), and muscular dystrophies (slowly progressive disease) 3. In two large observational studies, the mean age of onset has been reported to be 59 ± 9 and 61 years, respectively 9, 11. The cardinal symptom of this highly debilitating disease is the late‐onset steady acquisition of muscular weakness and atrophy over a long period of time whilst sensory function is completely preserved.…”

“…The cardinal symptom of this highly debilitating disease is the late‐onset steady acquisition of muscular weakness and atrophy over a long period of time whilst sensory function is completely preserved. The decline of muscle strength ranges between 3.5 and 5.5% per annum 9, 11. Unlike other myopathies, during which proximal muscles are initially affected, IBM shows early involvement of distal muscles.…”

“…The chronic disease progression of IBM makes it challenging to detect the condition at an early time point and on average there is a 5‐year delay in diagnosis 9, 39. Creatine kinase levels in serum can be normal to only mildly elevated and will not exceed 10‐fold increase above the upper limit of normal.…”

“…The underlying interrelationship between the inflammatory component of the disease and the observed multi‐protein aggregation remains elusive and subject to vigorous debate 3, 6, 7, 8. Unlike other inflammatory myopathies, IBM presents mainly refractory toward immunosuppressive therapy and at present, there is no effective treatment available 5, 9, 10. In this review, we will focus on the current knowledge about the interrelationship of inflammatory and myodegenerative pathomechanisms in IBM.…”

Sporadic inclusion body myositis: A review of recent clinical advances and current approaches to diagnosis and treatment

“…In the UK-based IBM-Net Project to identify outcome measures for clinical trials, a 27.9% decline in strength was found with QMT at one-year follow-up in a group of 23 patients and a 13.8% annual decline in the 10-point IBM Functional Rating Scale (IBM-FRS) and it was concluded that QMT and the IBM-FRS are the best indicators of disease progression (Jackson et al, 2008, Cortese et al, 2013. A longitudinal study of 136 IBM patients from two European Centres used a composite clinical weakness index (ICWI) to assess progression in a subgroup of 71 patients, and found a good correlation with other measures of strength and walking handicap (Benveniste et al, 2011). This study also identified male gender and older age at onset as adverse prognostic indicators with respect to progression of disability and walking handicap.…”