Single-centre, cross-sectional study on the factors and reasons for non-vaccination among patients with rheumatoid arthritis.

OBJECTIVES: We aimed to investigate the vaccination coverage and the factors associated with non-vaccination for vaccine-preventable diseases among patients with rheumatoid arthritis. METHODS: This single-centre, cross-sectional study was conducted in a 715-bed regional tertiary-care teaching hospital in Japan from 1 September to 30 November 2020. Vaccination status and the factors and reasons for not receiving the influenza vaccine, 23-valent pneumococcal polysaccharide vaccine (PPSV23), 13-valent pneumococcal conjugate vaccine (PCV13), and varicella vaccine live (VVL) were investigated. RESULTS: Among 991 patients, the vaccination coverage for the influenza vaccine, PPSV23, PCV13, and VVL was 62%, 46%, 14%, and 3%, respectively. The most common reasons for vaccine hesitancy were efficacy concerns for the influenza vaccine, safety concerns for the PPSV23 and PCV13, and both efficacy and safety concerns for the VVL. Younger age, no use of biologics or other hospital visits, and public assistance were factors significantly associated with non-vaccination for the influenza vaccine; younger age, short disease duration, and no visits to other hospitals for PPSV23; younger age, no hospitalisation, more experienced doctor, and no medical immunodeficiency for PCV13. CONCLUSIONS: We found that the factors associated with non-vaccination varied by vaccine type; therefore, vaccinations should be promoted with individualised strategies.

Clinical characteristics of rheumatoid arthritis patients complicated with pulmonary nontuberculous mycobacterial disease: A cross-sectional case series study.

OBJECTIVES: Pulmonary nontuberculous mycobacterial disease (pNTM) is a common pulmonary complication of rheumatoid arthritis (RA), but their association has rarely been researched. We aimed to reveal the clinical characteristics of RA with pNTM. METHODS: Among all the RA patients who visited Tenri hospital from April 2017 to March 2018, we enrolled those fulfilling the 2007 ATS/IDSA diagnostic criteria of pNTM, and sex- and age- matched control group at a ratio of 1:5. Demographic characteristics were compared between the two groups. RESULTS: Among 865 RA patients, 35 (4.0%) patients were complicated with pNTM. RA patients with pNTM had significantly lower BMI and higher rheumatoid factor (RF) and anti-citrullinated protein antibody (ACPA) positivity. Bronchiectasis was the most frequent lesion, followed by clusters of small nodules, patchy consolidation and cavity. Multivariable logistic regression analysis revealed bronchiectasis as a strong independent associated factor of pNTM. Treatment for pNTM was needed in 14 of the 35 (40%) RA patients with pNTM and sputum negative conversion was accomplished in 11 of the 14 cases (78.6%). CONCLUSIONS: RA patients with lower BMI, RF/ACPA positivity, and bronchiectasis were associated with pNTM. Treatment for pNTM may attain sputum negative conversion and radiological improvement in patients with RA.

TAFRO syndrome with a fatal clinical course following BNT162b2 mRNA (Pfizer-BioNTech) COVID-19 vaccination: A case report.

TAFRO syndrome is a rare disorder that manifests as thrombocytopenia, anasarca, fever, reticulin myelofibrosis, renal dysfunction, and organomegaly. Although this disease often follows a severe clinical course, the cause remains unknown. The coronavirus disease 2019 (COVID-19) pandemic is a major global problem. Vaccination against COVID-19 has been successful; however, there are concerns about severe adverse events. Herein, we report a rare presentation of TAFRO syndrome triggered by the COVID-19 vaccine with a fatal clinical course. A 42-year-old Japanese man presented to our hospital complaining of fever lasting for 2 weeks that occurred a day after receiving the BNT162b2 mRNA (Pfizer-BioNTech) COVID-19 vaccine. The patient had a low platelet count, ascites, reticulin myelofibrosis, renal failure, and lymphadenopathy and was diagnosed with TAFRO syndrome. Despite administering several immunosuppressive drugs, the condition did not improve. The patient repetitively developed and eventually died of bacteremia caused by multidrug-resistant Klebsiella pneumoniae. We highlight the first reported case of TAFRO syndrome after COVID-19 vaccination.

Polypharmacy prevalence and associated factors in patients with systemic lupus erythematosus: A single-centre, cross-sectional study.

OBJECTIVES: This study aimed to clarify factors associated with polypharmacy among patients with systemic lupus erythematosus. METHODS: This single-centre cross-sectional study was conducted by reviewing the medical records and questionnaire data of 261 systemic lupus erythematosus patients at a teaching hospital in Japan from 1 September to 30 November 2020. Polypharmacy was defined as the regular administration of five or more oral medications; excessive polypharmacy consisted of the regular use of ten or more oral medications. This study investigated 1) the prevalence of polypharmacy and excessive polypharmacy, 2) the distribution of medication types, and 3) factors associated with polypharmacy and excessive polypharmacy. RESULTS: The proportions of patients that exhibited polypharmacy and excessive polypharmacy were 70% and 19%, respectively. Polypharmacy was associated with older age, long duration of systemic lupus erythematosus, high disease activity, and administration of glucocorticoids or immunosuppressive agents. Excessive polypharmacy was associated with a higher updated Charlson comorbidity index, history of visits to multiple internal medicine clinics, and presence of public assistance. CONCLUSIONS: Polypharmacy and excessive polypharmacy in patients with systemic lupus erythematosus are related to medical aspects such as disease severity and comorbidities in addition to social aspects such as hospital visitation patterns and economic status.

Sustained discontinuation of infliximab with a raising-dose strategy after obtaining remission in patients with rheumatoid arthritis: the RRRR study, a randomised controlled trial.

OBJECTIVES: The aim of this study is to determine whether the 'programmed' infliximab (IFX) treatment strategy (for which the dose of IFX was adjusted based on the baseline serum tumour necrosis factor α (TNF-α)) is beneficial to induction of clinical remission after 54 weeks and sustained discontinuation of IFX for 1 year. METHODS: In this multicentre randomised trial, patients with IFX-naïve rheumatoid arthritis with inadequate response to methotrexate were randomised to two groups; patients in programmed treatment group received 3 mg/kg IFX until week 6 and after 14 weeks the dose of IFX was adjusted based on the baseline levels of serum TNF-α until week 54; patients in the standard treatment group received 3 mg/kg of IFX. Patients who achieved a simplified disease activity index (SDAI) ≤3.3 at week 54 discontinued IFX. The primary endpoint was the proportion of patients who sustained discontinuation of IFX at week 106. RESULTS: A total of 337 patients were randomised. At week 54, 39.4% (67/170) in the programmed group and 32.3% (54/167) in the standard group attained remission (SDAI ≤3.3). At week 106, the 1-year sustained discontinuation rate was not significantly different between two groups; the programmed group 23.5% (40/170) and the standard group 21.6% (36/167), respectively (2.2% difference, 95% CI -6.6% to 11.0%; p=0.631). Baseline SDAI <26.0 was a statistically significant predictor of the successfully sustained discontinuation of IFX at week 106. CONCLUSION: Programmed treatment strategy did not statistically increase the sustained remission rate after 1 year discontinuation of IFX treatment.

Serum matrix metalloproteinase levels in polymyositis/dermatomyositis patients with interstitial lung disease.

OBJECTIVE: We aimed to clarify the clinical significance of serum levels of MMPs in interstitial lung disease (ILD) complicated with PM/DM (PM/DM-ILD). METHODS: We retrospectively analysed serum levels of seven subsets of MMPs in 52 PM/DM-ILD patients diagnosed at Kyoto University Hospital or Tenri Hospital from January 2005 to December 2014. The patients were sub-grouped based on the presence of anti-amimoacyl-tRNA synthetase antibody (anti-ARS antibody), anti-melanoma differentiation-associated protein 5 antibody (anti-MDA5 antibody) or lack of the antibodies (ARS-ILD, MDA5-ILD and other-ILD groups, respectively) and independently analysed. Eighteen PM/DM patients without ILD and 55 healthy control were also analysed. Associations between serum levels of MMPs and clinical findings including mortality were analysed. RESULTS: Among the MMPs analysed, MMP-7 serum levels in the ARS-ILD group were significantly higher compared with those in any of the other groups of PM/DM patients or in healthy controls. On the other hand, in the MDA5-ILD group, serum MMP-7 levels >5.08 ng/ml were associated with worse overall survival both in univariate (P = 0.017; odds ratio 18.0; 95% CI 1.69, 192.00) and multivariate (P = 0.027; odds ratio 14.60; 95% CI 1.11, 192.00) analyses. Immunohistochemical analysis suggested that MMP-7 was expressed in type II alveolar epithelial cells adjacent to the fibrotic lesions. CONCLUSION: Serum MMP-7 levels were higher in anti-ARS antibody-positive PM/DM-ILD patients, while higher serum MMP-7 levels among anti-MDA5 antibody-positive PM/DM-ILD patients were associated with a worse prognosis. Fibrotic processes may be associated with the elevation of serum MMP-7 levels.

Tufted-angioma-like lesion associated with vascular endothelial growth factor and interleukin-6 in TAFRO syndrome: Is it a common histological feature of multicentric Castleman disease/POEMS syndrome?

The histology of skin lesions of TAFRO (thrombocytopenia, anasarca, reticulin fibrosis/renal failure, and organomegaly) syndrome has rarely been reported. We report herein two cases of TAFRO syndrome with characteristic vascular skin lesions. The lesions resembled a tufted angioma, although those of case 1 partially resembled a glomeruloid hemangioma, which was known as a specific lesion in POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, M-protein and skin changes), a variant of multicentric Castleman disease (MCD). The high titer of serum vascular endothelial growth factor and interleukin-6 could explain common characteristic vascular lesions in both TAFRO syndrome and POEMS syndrome/MCD.

Hypereosinophilic syndrome as a cause of fatal thrombosis: two case reports with histological study.

Herein we present two cases of hypereosinophilic syndrome with a unique clinical presentation. One patient showed severe systemic thrombosis with splenic rupture and the other patient showed finger gangrene with various systemic symptoms. Both patients were examined histologically, and several characteristics were noted. First, fresh or organized thrombosis with marked eosinophilic infiltration was observed in the cavity and walls of the thrombosed vessels. Second, many eosinophils showed degranulation and were positive for eosinophilic cationic protein on immunohistological examination. Third, the structures of thrombosed vessels were well preserved, which is not observed in systemic vasculitis. These patients exhibited no neoplastic features and were treated with prednisolone with excellent therapeutic results.

Long-term safety and efficacy of rituximab in 7 Japanese patients with ANCA-associated vasculitis.

OBJECTIVES: The safety and efficacy of rituximab were examined in a multicenter open-label pilot study in patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) in Japan. METHODS: Patients with refractory AAV were administered a rituximab infusion at a weekly dose of 375 mg/m(2) for 4 weeks. All patients also received oral daily prednisolone. The primary outcome was complete remission, which was defined as a Birmingham Vasculitis Activity Score (BVAS) of 0 or 1. RESULTS: The mean age of the 7 patients was 57 (range, 34-71) years. The mean follow-up period after rituximab treatment was 62.9 (range, 4.8-81) months. The mean BVAS at entry was 16.7 (range, 2-34). Complete remission occurred in all cases, except in 1 case in which the patient died, with a significant decline in BVAS from baseline at 12 months after initiation of rituximab. Rituximab reduced granulomatous orbital involvement in a patient with granulomatosis with polyangiitis. Relapse occurred in five patients. Adverse events included de novo hepatitis B in one patient, cancer (hepatocellular carcinoma and prostate cancer) in two patients, and transient visual disturbance, atypical mycobacterial infection, urinary tract infection, sepsis, and cytomegalovirus infection. Two patients died due to recurrent infections and airway obstruction, caused by an AAV lesion. CONCLUSIONS: Rituximab had a beneficial effect on refractory AAV in Japanese patients, but several adverse effects occurred during rituximab treatment.

An observational study to identify causative factors for not using hydroxychloroquine in systemic lupus erythematosus.

Hydroxychloroquine (HCQ) use is indicated for patients with systemic lupus erythematosus (SLE). Nevertheless, reports discussing the reasons for not prescribing HCQ are limited. We identified the factors that interfere with HCQ use in patients with SLE. This observational, single-center study included data from 265 patients with SLE in 2019. The patients were categorized into groups with and without a history of HCQ use. Between these groups, clinical characteristics were compared using univariate analysis and logistic regression models. Among the 265 patients, 133 (50.2%) had a history of HCQ use. Univariate analysis identified older age; longer disease duration; lower prednisolone dose, clinical SLE disease activity index 2000, and estimated glomerular filtration rate; higher C3 level; and lower anti-double-stranded DNA antibody concentration as HCQ non-use-related variables. Logistic regression models identified a positive association between HCQ non-use and longer disease duration (odds ratio [OR] 1.08), prednisolone dose ≤ 7.5 mg/day (OR 4.03), C3 level ≥ 73 mg/dL (OR 2.15), and attending physician having graduated > 10 years prior (OR 3.19). In conclusion, a longer disease duration, lower prednisolone dose, higher C3 level, and longer time since attending physicians' graduation correlated with HCQ non-use. Physicians and patients should be educated to facilitate HCQ use despite these factors.

Successful treatment of streptococcal toxic shock syndrome complicated by primary peritonitis and bilateral empyema in a healthy young woman: Identification of uncommon clone emm103 and novel sequence type 1363.

Streptococcal toxic shock syndrome (STSS) has a dramatic clinical course and high mortality rate. Here, we report a case of STSS complicated by primary peritonitis and bilateral empyema. A previously healthy young woman was diagnosed with STSS complicated by primary peritonitis and bilateral empyema. Blood culture results on admission were negative. Sever shock, respiratory failure, systemic inflammation, thrombocytopenia, renal failure, ascites, and pleural effusion occurred, mimicking thrombocytopenia, anasarca, fever, reticulin fibrosis/renal failure and organomegaly (TAFRO) syndrome. Retesting blood cultures identified Streptococcus pyogenes. Gram staining of ascites and pleural fluid indicated gram-positive cocci in chains. Antibiotics, immunoglobulins, and surgical intervention led to recovery without complications. Ex-post genotypic analyses showed uncommon emm103.0 (cluster E3) of emm long sequence (784 base) and novel sequence type 1363. STSS diagnosis can be difficult as it mimics other systemic inflammatory diseases. Therefore, it is crucial for clinicians to perform microbiological examinations from infection foci, even if the initial culture is negative.

Acquired generalized anhidrosis: review of the literature and report of a case with lymphocytic hidradenitis and sialadenitis successfully treated with cyclosporine.

We report a case of acquired generalized anhidrosis successfully treated with cyclosporine. A skin biopsy showed T cell infiltration around the sweat glands and labial biopsy revealed lymphoplasmacytic infiltration around the minor salivary gland, suggesting an underlying autoimmune disease such as Sjögren's syndrome. Administration of cyclosporine markedly improved the patient's condition and sympathetic skin response; thus cyclosporine may be effective for treating anhidrosis in patients with autoimmune disorders.

Factors and Reasons for Non-vaccination among Patients with Systemic Lupus Erythematosus: A Single-centre, Cross-sectional Study.

Objective This study aimed to clarify the vaccination coverage of vaccine-preventable diseases and the factors and reasons for non-vaccination among patients with systemic lupus erythematosus (SLE). Methods This single-centre, cross-sectional study was conducted from 1 September to 30 November 2020 in a 715-bed regional tertiary-care teaching hospital in Japan. A questionnaire survey was undertaken to investigate the vaccination status of patients with SLE, and the factors and reasons for not receiving the influenza vaccine, 23-valent-pneumococcal-polysaccharide vaccine (PPSV23), 13-valent pneumococcal conjugate vaccine (PCV13), varicella vaccine live (VVL), and recombinant zoster vaccine (RZV). Results The vaccination coverage for the influenza vaccine, PPSV23, PCV13, VVL, and RZV was 61%, 22%, 19%, 3.4%, and 0%, respectively, among 261 patients. The most common reason for vaccine hesitancy was 'efficacy concerns about vaccines' for the influenza vaccine and 'cost' for PPSV23 and PCV13. The factors significantly associated with non-vaccination were prescription of high-dose glucocorticoids and no history of visits to other internal medicine clinics for the influenza vaccine; a younger age and prescription of high-dose glucocorticoids for PPSV23; and a younger age, no medication with hydroxychloroquine, no history of hospitalisation in internal medicine, and extensive clinical experience of the doctor for PCV13. Conclusion These findings, which demonstrated that the factors and reasons for non-vaccination varied by vaccine type, suggest that individualised strategies should be used to promote vaccination in this population.

Prevalence and factors associated with polypharmacy among patients with rheumatoid arthritis: a single-centre, cross-sectional study.

OBJECTIVE: This study aimed to identify factors associated with polypharmacy, including social aspects, among patients with rheumatoid arthritis. METHODS: We conducted this single-centre, cross-sectional study at a 715-bed regional tertiary care teaching hospital in Japan from 1 September to 30 November 2020. Polypharmacy was defined as having five or more medications administered orally regularly, and excessive polypharmacy was defined as having 10 or more medications administered orally regularly. The prevalence of polypharmacy and excessive polypharmacy, distribution of medication types, and factors associated with polypharmacy and excessive polypharmacy were investigated among patients with rheumatoid arthritis. RESULTS: The proportions of polypharmacy and excessive polypharmacy were 61% and 15%, respectively, in 991 patients. Polypharmacy and excessive polypharmacy were associated with older age (odds ratio, 1.03 and 1.03, respectively), high Health Assessment Questionnaire Disability Index (odds ratio, 1.45 and 2.03, respectively), medication with glucocorticoids (odds ratio, 5.57 and 2.42, respectively), high Charlson comorbidity index (odds ratio, 1.28 and 1.36, respectively), and a history of hospitalisation in internal medicine (odds ratio, 1.92 and 1.87, respectively) and visits to other internal medicine clinics (odds ratio, 2.93 and 2.03, respectively). Moreover, excessive polypharmacy was associated with the presence of public assistance (odds ratio, 3.80). CONCLUSIONS: Considering that polypharmacy and excessive polypharmacy are associated with a history of hospitalisation and glucocorticoid medication in patients with rheumatoid arthritis, medications during hospitalisation should be monitored, and glucocorticoids should be discontinued. Key points • The proportion of polypharmacy (five or more medications administered orally regularly) was 61%. • The proportion of excessive polypharmacy (10 or more medications administered orally regularly) was 15%. • Medications during hospitalisation should be reviewed and examined, and glucocorticoids should be discontinued.

The Impact of Early Optimization of Infliximab Blood Concentrations >1 µg/mL on Therapeutic Effectiveness in Rheumatoid Arthritis.

BACKGROUND: Infliximab is a human-murine chimeric monoclonal IgG antibody against tumor necrosis factor that is used in combination with methotrexate for the treatment of moderate to severe rheumatoid arthritis (RA). The trough concentration of serum infliximab required to control disease activity in RA is ≥1 µg/mL, and we investigated whether this trough concentration can predict the effectiveness of RA treatment. METHODS: We retrospectively analyzed the cases of 76 patients with RA. The REMICHECK Q® (REMIQ) is a kit that can check for serum infliximab concentrations. Infliximab concentrations >1 µg/mL at 14 weeks after an initial infliximab induction is considered REMIQ-positive, otherwise considered REMIQ-negative. Here, we determined the retention rates and investigated the clinical and serologic features of REMIQ-positive and REMIQ-negative patients. RESULTS: At 14 weeks, significantly more of the REMIQ-positive patients (n = 46) were responders compared to the non-responders (n = 30). The retention rate at 54 weeks was also significantly higher in the REMIQ-positive group versus the negative group. After 14 weeks, more patients in the REMIQ-negative group were considered inadequate responders, and their infliximab doses were escalated. At baseline, the REMIQ-positive group had significantly lower C-reactive protein (CRP) levels compared to the negative group. Cox regression analysis with multiple variables showed that the positivity of REMIQ (hazard ratio [HR] 2.10 and 95% confidence interval [CI]: 1.55-5.71) at baseline was associated with the achievement of low disease activity. The positivities of rheumatoid factor and anti-CCP antibody at baseline were associated with the achievement of remission with infliximab treatment (HR 0.44, 95% CI: 0.09-0.82 and HR 0.35, 95% CI: 0.04-0.48, respectively). CONCLUSIONS: The results of this study suggest that the control of RA disease activity may be facilitated by using the REMIQ kit at 14 weeks to check whether it is necessary to increase a patient's infliximab dose to ensure a therapeutic blood concentration that will help the patient achieve low disease activity.

Radiological features and therapeutic responses of pulmonary nontuberculous mycobacterial disease in rheumatoid arthritis patients receiving biological agents: a retrospective multicenter study in Japan.

OBJECTIVE: This study was performed to evaluate the radiological features of and therapeutic responses to pulmonary disease caused by nontuberculous mycobacteria (NTM) in the setting of biological therapy for rheumatoid arthritis (RA). METHODS: We conducted a retrospective chart review of 13 patients from multiple centers who had developed pulmonary NTM disease during biological therapy for RA, including infliximab, etanercept, adalimumab, and tocilizumab. RESULTS: Most cases were asymptomatic or resulted in only common-cold-like symptoms. Abnormalities in computed tomography (CT) imaging were protean and frequently overlapped. The most predominant pattern was nodular/bronchiectatic disease (six cases), followed by alveolar infiltrate (three cases), cavitary disease (two cases), and pulmonary nodules (two cases). In most cases, pulmonary NTM disease had spread from a preexisting lesion; in particular, bronchial/bronchiolar abnormalities. In three cases, one or more nodular lesions with or without calcification were a focus of disease. Following the discontinuation of biological agents, most patients responded to anti-NTM therapy. Two patients showed no exacerbation in the absence of any anti-NTM therapy. In one patient, restarting tocilizumab therapy while continuing to receive adequate anti-NTM therapy produced a favorable outcome. In two other patients with a previous history of pulmonary NTM disease, introducing biological therapy led to recurrence, but anti-NTM therapy was effective in these patients. CONCLUSION: CT abnormalities of pulmonary NTM disease in RA patients receiving biological therapy were variable, but were not unique to this clinical setting. NTM disease can spread from preexisting structural abnormalities, even if they are minute. Contrary to our expectations, the therapeutic outcomes of pulmonary NTM disease were favorable in these patients.

Elevated White Blood Cell Count and Lactate Dehydrogenase Levels Are Important Markers for Diagnosing Relapse of Adult-onset Still's Disease under Tocilizumab Use.

We encountered a case of refractory adult-onset Still's disease (AOSD) with two relapses. Prednisolone and methotrexate were begun as induction therapy, resulting in the patient's first relapse during tapering of prednisolone. After the introduction of tocilizumab, she achieved remission. However, she experienced a second relapse following prednisolone tapering. While lactate dehydrogenase (LDH) levels and white blood cell (WBC) counts increased in both relapses, interleukin-6 (IL-6) suppression resulted in stable C-reactive protein and ferritin levels in the second relapse. A comparison of the two relapses indicated that increases in both WBC counts and LDH levels can aid in the diagnosis of AOSD relapse.

Lupus Aortitis Successfully Treated with Moderate-dose Glucocorticoids: A Case Report and Review of the Literature.

Lupus aortitis is a rare and potentially life-threatening disorder. Previous studies have reported the utility of high-dose systemic glucocorticoids or surgery as the treatment, although there have been no related controlled trials. We herein report a 49-year-old woman with a 35-year history of systemic lupus erythematosus who was diagnosed with aortitis. Her symptoms and laboratory and imaging abnormalities rapidly resolved upon the administration of moderate-dose glucocorticoids. We subsequently performed a literature review of similar cases to identify the appropriate treatment and discuss these cases. A study of further cases will be needed to identify the characteristics of patients who would benefit from moderate-dose glucocorticoid therapy.

Multicenter Prospective Study of the Efficacy and Safety of Combined Immunosuppressive Therapy With High-Dose Glucocorticoid, Tacrolimus, and Cyclophosphamide in Interstitial Lung Diseases Accompanied by Anti-Melanoma Differentiation-Associated Gene 5-Positive Dermatomyositis.

OBJECTIVE: Interstitial lung disease (ILD) accompanied by anti-melanoma differentiation-associated gene 5 (anti-MDA-5)-positive dermatomyositis (DM) is often rapidly progressive and associated with poor prognosis. Because there is no established treatment, we undertook this study to prospectively evaluate the efficacy and safety of a combined immunosuppressive regimen for anti-MDA-5-positive DM patients with ILD. METHODS: Adult Japanese patients with new-onset anti-MDA-5-positive DM with ILD (n = 29) were enrolled at multiple study centers from 2014 to 2017. They were treated with a regimen of high-dose glucocorticoids (GCs), tacrolimus, and intravenous cyclophosphamide (IV CYC). Plasmapheresis was used if a patient's condition worsened after the regimen started. The primary end point was 6-month survival, which was compared between this group of patients and a historical control group (n = 15) consisting of anti-MDA-5-positive DM patients with ILD who received step-up treatment (high-dose GC and stepwise addition of immunosuppressant). Secondary end points were 12-month survival rate, adverse events, and changes in laboratory data. RESULTS: The combined immunosuppressive regimen group showed significantly higher 6-month survival rates than the step-up treatment group (89% versus 33%; P < 0.0001). Over a period of 52 weeks, improvements in anti-MDA-5 titers, serum ferritin levels, vital capacity, and chest high-resolution computed tomography scores were observed. The combined immunosuppressive regimen group received IV CYC nearly 20 days earlier with shorter intervals and tended to receive plasmapheresis more often than patients undergoing step-up treatment. Cytomegalovirus reactivation was frequently observed over 52 weeks. CONCLUSION: A combined immunosuppressive regimen is effective for anti-MDA-5-positive DM patients with ILD. Plasmapheresis can be used for additional effect in intractable disease. Patients should be carefully monitored for opportunistic infections during treatment.