The present study describes the results of a reply-paid postcard questionnaire survey directed at attending physicians. One limitation is any genetic testing was not mandatory for the inclusion criteria of this study. We selected the patients fulfilling the “definite” or “probable” sIBM criteria by clinical and biopsy (Ref.) which reduce the possibility of including myofibrillar myopathy, GNE myopathy or VCP myopathy. Reply rate is around 25% for the reply-paid postcard questionnaire for neurologists. In Japan, diagnosis of the sIBM patients would be examined mostly at either the National Center or University Hospitals. Although the percentage is small, most of the physicians who underwent muscle biopsy at university or central regional hospitals might reply and non-responders might not see the patients. Over the last 10 years, we repeatedly performed a nationwide survey. We found the number of patients with sIBM is increasing in Japan (Table 4), particularly increasing linearly among individuals born after the 1920s. Previously, we performed a retrospective survey involving Japanese patients with sIBM who were diagnosed at the NCNP . Moreover, another research group from Japan reported an increasing number of patients sIBM . One possible reason for this trend is the increasing awareness of sIBM among medical doctors. Doctors of other specialties, such as orthopedic surgeons or otolaryngologists, can also diagnose sIBM, and its prevalence is likely to increase among elderly people in the near future. Inability to stand-up, cane-dependent gait, inability to open a plastic bottle, choking on food, and being wheelchair-bound are significant sIBM milestones. In the disease course of sIBM, patient sometimes can’t stand-up by themselves because of the weakness of quadriceps muscle, but can walk with cane. This increasing trend is easily observed as the patient aged. Aspiration pneumonia and being wheelchair-bound occurred approximately 10 years after sIBM onset (Table 5 and Fig. 1). These milestones are similar to those previously reported [2, 6, 7], and can help inform the patients about the disease. In outpatient clinics, improving mobility using a walking device or chair should be emphasized for the first 5 years after sIBM onset. On the other hand, paying greater attention to dysphagia and wheelchair requirement should be the focus of the latter 5 years. Additionally, a fraction of the patients were observed to initially have partial or single sIBM symptom (e.g., dysphagia or inability to flex fingers), which may remain isolated for several years [15, 16]. No correlation was found between modified IBMFRS and the parameters examined (data not shown). These facts indicate that sIBM is a heterogeneous disease. Since the questionnaire survey was conducted in a cross-sectional manner, a time-course study should be planned to further investigate this correlation. The age at the time of the study was negatively, but very weakly, correlated with modified IBMFRS, suggesting that aged patient manifest impairments in various activities of daily living. Follow-up time course analysis is desirable in the future study .
In the present study, none of the patients exhibited signs of apparent dementia (Fig. 3a), as subjectively evaluated. This is consistent with the findings of our previous survey . Further structured questionnaire in detail should be examined to analyze the severity of dementia. On the other hand, inclusion body myopathy with Paget’s disease of the bone and frontotemporal dementia or multisystem proteinopathy coexisted with dementia [20, 22], indicating that sIBM should be separated from diseases associated with genetic mutations.
Eight patients (7.5%) were anti-HCV antibody positive, and three underwent interferon treatment before sIBM onset. The prevalence of HCV was estimated around 2% over 70 years of age in Japan . Compared to the national scale data, the prevalence ratio of HCV antibody positive patients seemed to be rather high. This suggests that for treating sIBM, information pertaining to the viral infection and immune modulation therapy should be collected.
“Can rehabilitation slow sIBM progression?” is a frequently asked clinical question. In the present study, we observed no significant differences between patients with and without involvement in sIBM rehabilitation programs in terms of the course of sIBM, as evaluated by the time required to exhibit inability to stand-up. A recent study reported that 12 weeks of low-load, blood flow-restricted, resistance training did not improve self-reported or objective physical function among patients with sIBM . The authors claimed that the training protocol had a preventive (retaining) effect on the sIBM-related decline in leg muscle strength, which may aid the long-term preservation of physical function and postpone the need for healthcare assistance, and maintain the ADLs. The Hybrid Assistive Limb has been approved for sIBM rehabilitation in Japan. However, prospective evaluations with structured questionnaire and clinical trial are necessary to validate this new therapeutic strategy.
Our results indicate subjective symptom improvement through immune-mediated therapies. We also found that patients in the IVIG-treated cohort required longer time to exhibit the inability to stand-up (Fig. 4b). However, there are several limitations in this result. Since this was a retrospective analysis, there were both selection and observational biases. The timing and term of administration were not unified. The small number of patients with the milestone of the wheelchair bound might affect the result of the no correlation between therapy and wheelchair bound. Analysis of larger number of patients with prospective unified protocol is mandatory.
In a previous study, IVIG improved four cases of sIBM in terms of dysphagia in 8 months . Although the effect of IVIG does not last long, in Australia, patients with sIBM with severe dysphagia are covered by insurance . Benveniste et al. reported that 71 (52%) patients received immunosuppressive treatments such as prednisolone (91.5%) or other immunomodulatory drugs, including IVIG, methotrexate, or azathioprine (64.8%), for a median duration of 40.8 months. The heterogeneity of sIBM might mask the effect of drugs such as bimagrumab, leading to clinical trial termination. For the slowly progressive neuromuscular disease like sIBM, it would be practical to monitor only a small number of evaluation item (e.g. unable to stand-up) and follow-up for longer period.
Developed countries such as Japan have an aged population, and mid- to older-aged partners of patients with sIBM often lack physical strength and may also have a disease of their own. Our previous questionnaire also revealed several qualitative aspects pertaining to caregivers, typically spouses, and their difficulty in managing sIBM, given its long course. In this study, 70 patients applied for the designated incurable disease medical expenses subsidy program by Japanese government. Clearly, this has an impact on caregivers who themselves require societal supports. However, 47 patients (44.3%) still reported psychological/mental and financial anxieties.
The present study has several limitations, as previously mentioned. The study used a retrospective and cross-sectional design and, thus, could not determine causal relationships. A longitudinal study should be conducted to address this issue.