Multicenter questionnaire survey for sporadic inclusion body myositis in Japan

We surveyed patient data for 146 cases diagnosed at a number of centers across Japan to elucidate the cross-sectional profile of patients affected by sIBM in Japan. We also issued a questionnaire for 67 patients and direct caregivers to further elucidate the natural history of the disease. Through these surveys, we described the cross-sectional profiles of sIBM in Japan for the first time in the Asian countries. We found the same issues in the clinical practices of sIBM in Japan similar to Western countries.

Interestingly, a rather high percentage of patients were seropositive for HCV (n?=?16) and HTLV-1 (n?=?8) in our multicenter survey, corroborating the interaction between viral infection and the pathophysiology of sIBM, as mentioned previously. Eleven patients with HTLV-1–associated IBM were reported in the endemic area in Japan [8]. The prevalence of HTLV-1 infection in sIBM is higher than in the general population, compared with the prevalence in general in Japanese people aged 60 to 64 years in 2006–2007, which was estimated to be 1.5 % in men and 1.7 % in women [9]. Moreover, Uruha et al. reported that a significantly higher number of patients with sIBM (28 %) had anti-HCV antibodies than patients with polymyositis (4.5 %; odds ratio, 8.2) and the general Japanese population in their 60s (3.4 %) [9]. A pathomechanistic link between sIBM and HTLV1/HCV infection merits further research.

For the purpose of early intervention in clinical trials, early diagnosis of disease is important. Some of the patients in our study visited several physicians and the average time from date of onset to diagnosis was 55.52 months. Some patients show isolated weakness of finger flexors 3 years after onset but were diagnosed with sIBM in muscle biopsy 6 years after onset [10]. Some patients underwent repeat biopsy of the muscle because of the lack of findings related to rimmed vacuoles or other pathological markers. It is important to evaluate which muscle should be biopsied using CT and MRI. Currently, the utility of a new auto-antibody targeting cytosolic 5?-nucleotidase 1A (cN-1A) in the serum of patients with sIBM has recently been published [11]. The diagnostic utility for differentiating between sIBM, other forms of myositis, and other neuromuscular diseases requires further examination. Reliable positive markers for sIBM are necessary for the early diagnosis in future clinical trials.

As shown in Fig. 5, clinical diagnosis tends to be different from sIBM in early diagnosis. The importance of muscle biopsy is integral to the correct diagnosis. A clinical trial of bimagrumab is ongoing [12]. Transforming growth factor beta superfamily signaling, at least through ActRII, is implicated in the pathophysiology of sIBM. The inhibition of ActRII increased muscle mass and function in this pilot trial, thus, offering a potential novel treatment of sIBM [13]. Benveniste et al. reported that 71 (52 %) patients received immunosuppressive treatments such as prednisolone in 91.5, and 64.8 % were treated with other immunomodulatory drugs, including IVIgs, methotrexate, or azathioprine, for a median duration of 40.8 months [14]. This study confirms immunosuppressive treatments do not ameliorate the natural course of disease, thus, confirming findings from smaller studies. The decision to terminate conventional immunosuppressive treatment might be considered if there is no apparent beneficial effect after the trial, during a certain period of therapy.

In one of the abovementioned studies [15], euthanasia was requested by three patients, and in another three, continuous deep sedation was applied. The fact that end-of-life care interventions were used in six patients (13 %) reflects the severe disability and loss of quality of life at the end stage of this disease [15]. sIBM is a chronic progressive disorder, leading to major disabilities at the end stage of the disease because of extensive muscle weakness. Our questionnaire survey also revealed several qualitative aspects relating to caregivers who were typically spouses, and the difficulty in managing the disease because of its long duration (Fig. 6). Clearly, this impacts upon caregivers who themselves require societal support.

It is notable that 73 % of survey respondents described the anxiety and psychological/mental aspect of the disease. Developed countries, including Japan, have an aged society, and at mid-to-older age the partners of sIBM patients often lack physical strength and may have a disease. Some patients complained about the bleak outlook of sIBM therapy. A total of 57 % of patients mentioned problems managing finances. In Japan, there was no financial support for patients affected by sIBM at the time of the questionnaire; support for patients with intractable disease started in 2015. It is highly important to prepare social resources in developed countries for rare intractable diseases, including sIBM.

The present study has several limitations. First, the study used a retrospective and cross-sectional design, which cannot determine causal relationships. A longitudinal study should be conducted to address this issue. One group performed a follow-up study of 64 patients with sIBM who participated in a national epidemiological study in the Netherlands [15]. Case histories were recorded and manual and quantitative muscle tests as well as laboratory tests were performed at baseline and 12 years (median) after the first outpatient visit. Forty-six patients died during the follow-up period. The 15 surviving patients had a mean disease duration of 20 years. The mean decline in strength was recorded to be between 3.5 and 5.4 % per year according to the manual muscle testing and quantitative muscle testing criteria, respectively. Disorders of the respiratory system were the most common cause of death. In another study, 136 patients (57 % males; average age, 61 years at disease onset) were included [14]. During their follow-up, 75 % patients had significant walking difficulties and 37 % used a wheelchair (after a median duration of 14 years from the onset). Compared to these studies, a rather low rate of patients with finger flexor weakness or asymmetric weakness was described in our survey. This could be because the weakness is masked by compensatory mechanisms by lumbricals/FDS or not noticed by physicians without examining the FDP specifically. The cross-sectional nature of our study might affect the lower rate of symptoms. The overall demographic details of patients are similar between Japan and Western countries.

The other limitation of this study was that we should have included in the questionnaires for both patients and caregivers detailed questions on the functional ability to swallow [16] and the form of the consumed food (e.g., whether the meal was minced) in the questionnaire for both the patients and caregivers. Aspiration pneumonia is the common complication for sIBM and can sometimes be fatal. More detailed questions (e.g., how much cheese was eaten per week) with annual follow-up would be helpful in any future study.