Research activity information

• Oct. 2024 Japan College of Rheumatology, APLAR 2024 Travel Award at JCR, Bacteremia and associated factors in rheumatoid arthritis patients in a single center

  IKU SHIRASUGI

• Successful salvage treatment with baricitinib for macrophage activation syndrome complicating adult-onset Still’s disease during interleukin-6 inhibition: A case report and literature review

  Kazuma Nishisaka, Yo Ueda, Iku Shirasugi, Hirotaka Yamada, Takaichi Okano, Keisuke Nishimura, Sho Sendo, Jun Saegusa

  Jun. 2026, Modern Rheumatology Case Reports

  Scientific journal


• Clinical outcomes of molecular-targeted therapies for rheumatoid arthritis: comparison between orthopaedic surgeons and rheumatologists in the multicenter retrospective ANSWER cohort

  Yuki Etani, Yasutaka Okita, Kohei Tsujimoto, Takaaki Noguchi, Koichi Murata, Takayuki Fujii, Iku Shirasugi, Mai Yamashita, Koji Nagai, Ayaka Yoshikawa, Motomu Hashimoto, Tadashi Okano, Yuji Nozaki, Tetsu Itami, Yonsu Son, Hidehiko Makino, Wataru Yamamoto, Atsushi Kumanogoh, Seiji Okada, Ken Nakata, Kosuke Ebina

  Jun. 2026, Clinical Rheumatology

  Scientific journal


• Real-world comparison of herpes zoster risk among five Janus kinase inhibitors in rheumatoid arthritis: the ANSWER cohort study

  Yuki Etani, Yasutaka Okita, Yuichi Maeda, Kohei Tsujimoto, Takaaki Noguchi, Ryu Watanabe, Motomu Hashimoto, Iku Shirasugi, Naoki Nakano, Yuji Nozaki, Chisato Ashida, Yonsu Son, Hidehiko Makino, Yumiko Wada, Ayaka Yoshikawa, Takayuki Fujii, Wataru Yamamoto, Atsushi Kumanogoh, Seiji Okada, Ken Nakata, Kosuke Ebina

  May 2026, Joint Bone Spine

  Scientific journal


• Differential Impact of Concomitant Methotrexate and Glucocorticoids Dosages on Biologics and JAK Inhibitors: The ANSWER Cohort Study.

  Kosuke Ebina, Yuki Etani, Yasutaka Okita, Kohei Tsujimoto, Yuichi Maeda, Takaaki Noguchi, Makoto Hirao, Koichi Murata, Takayuki Fujii, Motomu Hashimoto, Tadashi Okano, Takuya Kotani, Koji Nagai, Takaichi Okano, Iku Shirasugi, Ryota Hara, Yonsu Son, Hideki Amuro, Masaki Katayama, Shotaro Tachibana, Shinya Hayashi, Wataru Yamamoto, Atsushi Kumanogoh, Ken Nakata, Seiji Okada, Akira Onishi

  AIM: This multicenter retrospective study evaluated the differential impact of concomitant methotrexate (MTX) and glucocorticoids (GCs) administration by dosage on the effectiveness and safety of biological disease-modifying antirheumatic drugs (bDMARDs) and Janus kinase inhibitors (JAKi) in a real-world cohort of patients with rheumatoid arthritis, adjusting for clinical backgrounds variables. METHODS: The study included 3751 treatment courses (bDMARD- or JAKi-naïve cases, 48.9%; tumor necrosis factor inhibitors: 1668; tocilizumab [TCZ]: 865; abatacept [ABT]: 825; JAKi: 393). Hazard ratios for treatment retention were calculated using multivariate Cox proportional hazards models, adjusted for potential confounders. Improvement in the clinical disease activity index (ΔCDAI) with each formulation was analyzed using mixed-effects models for repeated measures, stratified by concomitant MTX and GCs dosages. RESULTS: Compared to MTX(-), a lower dose of MTX (< 10 mg/week) was associated with significant improvement in ΔCDAI with golimumab (GLM), TCZ, and JAKi and reduced discontinuation due to ineffectiveness of etanercept (ETN). A higher MTX dose (≥ 10 mg/week) demonstrated a similar trend. Compared to GCs(-), a lower dose of GCs (≤ 5 mg/day; prednisolone equivalent) was associated with a diminished ΔCDAI with GLM and an increased discontinuation due to ineffectiveness of ADA and GLM. A higher dose of GCs (> 5 mg/day) was associated with increased discontinuation due to safety with ETN, CZP, and JAKi. CONCLUSIONS: The effects of concomitant MTX and GCs dosages on the effectiveness and safety of biologics and JAKi vary among agents. MTX did not mitigate safety issues, and GCs did not enhance effectiveness of any agents, regardless of dosage.

  Jul. 2025, International journal of rheumatic diseases, 28(7) (7), e70351, English, International magazine

  Scientific journal


• Sustained efficacy of second-line JAK inhibitors in patients with rheumatoid arthritis: insights from the ANSWER cohort

  Kohei Tsujimoto, Kosuke Ebina, Satomi Okamura, Yasutaka Okita, Yuki Etani, Wataru Yamamoto, Akira Onishi, Hideo Onizawa, Iku Shirasugi, Naoki Nakano, Takuya Kotani, Yuri Hiramatsu, Motomu Hashimoto, Tadashi Okano, Yuji Nozaki, Chisato Ashida, Yonsu Son, Akihiro Tanaka, Ryota Hara, Seiji Okada, Atsushi Kumanogoh

  OBJECTIVES: This multicentre, retrospective study aimed to evaluate differences in drug continuation rates and efficacy between first- and second-line use of biological DMARDs (bDMARDs) and Janus kinase inhibitors (JAKi) after failure of the initial therapy in real-world RA settings. METHODS: Data from an observational multicentre registry of patients with RA in Japan were analysed, encompassing 5900 treatment courses (4046 bDMARD/JAKi-naïve cases and 1854 second-line cases). Gray's tests were used to compare the cumulative incidence function (CIF) for drug discontinuation, considering discontinuation due to remission as a competing risk. Competing risk analysis using Fine-Gray model was conducted to analyse the hazard ratios after adjusting for potential confounders. Changes in the Clinical Disease Activity Index (ΔCDAI) and disease activity score (ΔDAS28-CRP) were assessed at each time point compared with baseline using a linear mixed model with covariate adjustments. RESULTS: Among the TNF inhibitors, IL-6 inhibitors, Cytotoxic T-lymphocyte associated protein 4 (CTLA4) and JAKi, only JAKi showed no significant difference in CIF of first- and second-line treatments. Competing risk analysis showed that consistent with the CIF analysis, second-line treatment influenced the drug continuation rates for all drugs except for JAKi. In analysing CDAI and DAS28-CRP trends using a linear mixed model, JAKi demonstrated similar efficacy as first- and second-line therapy, unlike other drugs. CONCLUSIONS: JAKi maintained continuation rates and efficacy in second-line treatment compared with first-line treatment, which is potentially advantageous over bDMARDs for patients with RA who require a change in initial therapy.

  Jul. 2025, Rheumatology, 64(7) (7), 4207 - 4217, English, International magazine

  Scientific journal


• Real-world comparative study of the efficacy of Janus kinase inhibitors in patients with rheumatoid arthritis: the ANSWER cohort study.

  Shinya Hayashi, Shotaro Tachibana, Toshihisa Maeda, Mai Yamashita, Iku Shirasugi, Yuzuru Yamamoto, Hirotaka Yamada, Takaichi Okano, Keisuke Nishimura, Yo Ueda, Sadao Jinno, Jun Saegusa, Wataru Yamamoto, Koichi Murata, Takayuki Fujii, Kenichiro Hata, Ayaka Yoshikawa, Kosuke Ebina, Yuki Etani, Naofumi Yoshida, Hideki Amuro, Motomu Hashimoto, Ryota Hara, Masaki Katayama, Tadashi Okano, Ryosuke Kuroda

  OBJECTIVE: This multicentre, retrospective study compared the efficacy and safety of tofacitinib, baricitinib, peficitinib and upadacitinib in real-world clinical settings after minimizing selection bias and adjusting the confounding patient characteristics. METHOD: The 622 patients were selected from the ANSWER cohort database and treated with tofacitinib (TOF), baricitinib (BAR), peficitinib (PEF) or upadacitinib (UPA). The patient's background was matched using propensity score-based inverse probability of treatment weighting (IPTW) among four treatment groups. The values of Clinical Disease Activity Index (CDAI), C-reactive protein (CRP), and modified Health Assessment Questionnaire (mHAQ) after drug initiation and the remission or low disease activity (LDA) rates of CDAI at 6 months after drug initiation were compared among the four groups. Further, the predictive factor for TOF and BAR efficacy was analysed. RESULTS: The retention and discontinuation rates until 6 months after drug initiations were not significantly different among the four JAK inhibitors treatment groups. Mean CDAI value, CDAI remission rate, and CDAI-LDA rate at 6 months after drug initiation were not significantly different among treatment groups. Baseline CDAI (TOFA: OR 1.09, P < 0.001; BARI: OR 1.07, P < 0.001), baseline CRP (TOFA: OR 1.32, P = 0.049), baseline glucocorticoid dose (BARI: OR 1.18, 95% CI 1.01-1.38, P = 0.035), a number of previous biological or targeted synthetic disease-modifying antirheumatic drugs (biological/targeted synthetic DMARDs) (BARI: OR 1.36, P = 0.004) were predictive factors for resistance to CDAI-LDA achievement to JAK inhibitor treatment. CONCLUSION: The efficacy and safety of TOF, BAR, PEF and UPA were not significantly different for the treatment of patients with rheumatoid arthritis.

  Nov. 2024, Rheumatology (Oxford, England), 63(11) (11), 3033 - 3041, English, International magazine

  Scientific journal


• Predictive factors and treatment outcomes associated with difficult-to-treat rheumatoid arthritis conditions: the ANSWER cohort study.

  Ryu Watanabe, Kosuke Ebina, Takaho Gon, Tadashi Okano, Koichi Murata, Kosaku Murakami, Yuichi Maeda, Sadao Jinno, Iku Shirasugi, Yonsu Son, Hideki Amuro, Masaki Katayama, Ryota Hara, Kenichiro Hata, Ayaka Yoshikawa, Wataru Yamamoto, Shotaro Tachibana, Shinya Hayashi, Yuki Etani, Masao Katsushima, Kazuo Fukumoto, Shinsuke Yamada, Motomu Hashimoto

  OBJECTIVES: To investigate the predictive factors for difficult-to-treat rheumatoid arthritis (D2T RA) and assess the efficacy of biologic DMARDs (bDMARDs) and Janus kinase inhibitors (JAKi). METHODS: Retrospective analysis was conducted on data from the ANSWER cohort comprising 3623 RA patients treated with bDMARDs or JAKi in Japan. Multivariate Cox proportional hazards modelling was used to analyse the hazard ratios (HRs) for treatment retention. RESULTS: Of the 3623 RA patients, 450 (12.4%) met the first two criteria of the EULAR D2T RA definition (defined as D2T RA in this study). Factors contributing to D2T RA included age over 75 (compared with those under 65, hazard ratio [HR] = 0.46; 95% CI: 0.31, 0.69), higher rheumatoid factor (RF) titres (HR = 1.005; 95% CI: 1.00, 1.01), higher clinical disease activity index (HR = 1.02; 95% CI: 1.01, 1.03), lower methotrexate dosage (HR = 0.97; 95% CI: 0.95, 0.99), and comorbidities like hypertension (HR = 1.53; 95% CI: 1.2, 1.95) and diabetes (HR = 1.37; 95% CI: 1.09, 1.73). Anti-IL-6 receptor antibodies (aIL-6R, HR = 0.53; 95% CI: 0.37, 0.75) and JAKi (HR = 0.64; 95% CI: 0.46, 0.90) were associated with fewer discontinuations due to ineffectiveness compared with TNF inhibitors. Oral glucocorticoid usage (HR = 1.65; 95% CI: 1.11, 2.47) was linked to increased discontinuation due to toxic adverse events. CONCLUSION: Younger onset, higher RF titres, and comorbidities predicted D2T RA development. For managing D2T RA, aIL-6R and JAKi exhibited superior drug retention.

  Sep. 2024, Rheumatology (Oxford, England), 63(9) (9), 2418 - 2426, English, International magazine

  Scientific journal


• Safety of Janus kinase inhibitors compared to biological DMARDs in patients with rheumatoid arthritis and renal impairment: the ANSWER cohort study.

  Yoichi Nakayama, Akira Onishi, Wataru Yamamoto, Ayaka Yoshikawa, Hideyuki Shiba, Naofumi Yoshida, Yonsu Son, Iku Shirasugi, Toshihisa Maeda, Masao Katsushima, Motomu Hashimoto, Yuki Etani, Tetsu Itami, Yuji Nozaki, Hideo Onizawa, Takayuki Fujii, Kosaku Murakami, Koichi Murata, Masao Tanaka, Shuichi Matsuda, Akio Morinobu

  Data on the safety of Janus kinase inhibitors (JAKis) in patients with renal impairment are lacking. This study aimed to investigate the safety of JAKis compared to biological (b) DMARDs in patients with rheumatoid arthritis (RA) and renal impairment. We used a multi-centre observational registry of patients with RA in Japan (the ANSWER cohort). We assessed the drug retention rates of b/targeted synthetic DMARDs with different modes of action (tumour necrosis factor inhibitors (TNFis), immunoglobulins fused with cytotoxic T-lymphocyte antigen (CTLA-4-Ig), interleukin-6 receptor inhibitors (IL-6Ris), and JAKis) in patients with RA stratified by pre-treatment estimated glomerular filtration rate (eGFR) levels. The time to discontinuation of bDMARDs or JAKis was analysed using a multivariate Cox proportional hazards model This study included 3775 patients, who were classified into three groups (the normal group (eGFR ≥ 60 mL/min/1.73 m2): 2893 patients; CKDa group (eGFR 45-60 mL/min/1.73 m2): 551; and CKDb group (eGFR < 45 mL/min/1.73 m2): 331). In the CKDb group, the 12-month drug retention rate due to adverse events (AE) was the lowest in patients treated with JAKi (TNFi: 93.1%; IL-6Ri: 94.1%; CTLA-4-Ig: 92.3%; JAKi: 75.1%). In the normal and CKDa groups, drug retention rates due to AE were similar among patients treated with bDMARDs and JAKi. In contrast, drug retention rates due to inefficacy were similar between bDMARDs and JAKis in all groups. In the Cox-proportional model, in the CKDb group, TNFi, IL-6Ri, and CTLA-4-Ig showed lower incidence of drug discontinuation due to AE than JAKis (TNFi: hazard ratio = 0.23 (95% confidence interval 0.09-0.61), IL-6Ri: 0.34 (0.14-0.81), CTLA-4-Ig: 0.36 (0.15-0.89)). JAKis showed the lowest drug retention due to AE in patients with moderate-to-severe and severe renal impairment (eGFR < 45 mL/min/1.73 m2). Physicians should pay more attention to renal function when using JAKis than when using bDMARDs.

  May 2024, Clinical and experimental medicine, 24(1) (1), 97 - 97, English, International magazine

  Scientific journal


• Association of large joint involvement at the start of biological disease-modifying antirheumatic drugs and Janus kinase inhibitors with disease activity and drug retention in patients with rheumatoid arthritis: The ANSWER cohort study.

  Iku Shirasugi, Akira Onishi, Keisuke Nishimura, Wataru Yamamoto, Kosaku Murakami, Hideo Onizawa, Yuichi Maeda, Kosuke Ebina, Yonsu Son, Hideki Amuro, Masaki Katayama, Ryota Hara, Koji Nagai, Yuri Hiramatsu, Motomu Hashimoto, Tadashi Okano, Toshihisa Maeda, Shinya Hayashi, Sho Sendo, Sadao Jinno, Yuzuru Yamamoto, Hirotaka Yamada, Yo Ueda, Jun Saegusa

  AIM: To investigate the association of large joint involvement (LJI) with disease activity and drug retention in patients with rheumatoid arthritis (RA) who started receiving a biological disease-modifying antirheumatic drug or Janus kinase inhibitor. METHODS: Patients with RA from a Japanese multicenter observational registry were enrolled. Our definition of large joints included the shoulder, elbow, hip, knee, and ankle joints. Linear mixed-effects models were used to examine changes in the clinical disease activity index (CDAI) score at Week 24 as the primary outcome, and drug retention rates were compared between patients with and without LJI using Cox proportional hazards models. We examined the potential effect modifications of changes in the CDAI by baseline characteristics. RESULTS: Overall, 2507 treatment courses from 1721 patients were included (LJI, 1744; no LJI, 763). Although LJI was associated with significantly higher changes in CDAI from baseline at Week 24 (difference in change in CDAI: -5.84 [-6.65 to -5.03], p < .001), CDAI was significantly higher in patients with LJI over time. Retention rates were similar in both groups. The association of LJI with changes in disease activity was more prominent in patients with a short disease duration, negative anti-citrullinated peptide antibodies, and interleukin-6 receptor inhibitor (IL-6Ri) use. CONCLUSION: Although LJI was associated with a greater reduction in disease activity from baseline, higher disease activity at baseline was not offset over time in patients with LJI, demonstrating that LJI is an unfavorable predictor. An early treat-to-target strategy using an IL-6Ri may be beneficial for patients with LJI.

  Mar. 2024, International journal of rheumatic diseases, 27(3) (3), e15097, English, International magazine

  Scientific journal


• Severe Lupus Myocarditis Preceded by Mesalazine-induced Lupus.

  Mai Yamashita, Keisuke Nishimura, Iku Shirasugi, Yoshihide Ichise, Yo Ueda, Jun Saegusa

  In drug-induced lupus (DIL), symptoms similar to those of systemic lupus erythematosus (SLE) usually resolve after discontinuation of the offending drug. A 41-year-old-woman with a history of ulcerative colitis presented with polyarthritis and myositis and was positive for anti-double stranded (ds) DNA IgG antibody. After discontinuation of mesalazine, the symptoms resolved, and the antibody titer decreased. The patient was diagnosed with DIL. Six months later, lupus myocarditis developed. After treatment with glucocorticoids, cyclophosphamide, intravenous immunoglobulin, and an intra-aortic balloon pump, she showed dramatic improvement. Patients with DIL and an immunological predisposition, such as anti-dsDNA antibodies, may have SLE and should be carefully monitored.

  Mar. 2023, Internal medicine (Tokyo, Japan), 62(6) (6), 929 - 933, English, Domestic magazine

  Scientific journal


• Demographic, Physical, and Psychological Determinants of Patient Experience with Subcutaneous Self-Injection in Patients with Rheumatoid Arthritis: Structural Equation Modeling Approach.

  Akira Onishi, Maiko Kaizu, Iku Shirasugi, Tomoko Yagyu, Yo Ueda, Yoshitada Sakai, Yasushi Miura, Jun Saegusa

  PURPOSE: To achieve a better patient experience with self-injection, an assessment of potential demographic, physical, and psychological barriers is necessary. The aim of this study was to examine the demographic, physical, and psychological characteristics associated with the experiences of self-injection in patients with rheumatoid arthritis (RA). PATIENTS AND METHODS: In this study, overall patient experience with subcutaneous self-injection was assessed using the Self-Injection Assessment Questionnaire. Upper limb function was assessed using the three domains of the Health Assessment Questionnaire associated with upper extremity disability (dressing and grooming, eating, and grip). Structural equation modeling was used to estimate the association between the demographic and clinical characteristics of patients with RA and their experiences with self-injection in the theoretical model. RESULTS: Data from 83 patients with RA were analyzed. Compared with younger patients, elderly patients were more likely to experience lower self-confidence, self-image, and ease of use. Female patients had lower ease of use than male patients. In terms of upper limb function, patients with more difficulty in performing activities of daily living were more likely to have a lower self-image. Self-injection perceptions before learning the method of injection, such as fear of needles and anxiety about self-injection, were associated with post-injection feelings, injection site reactions, self-confidence, and ease of use. CONCLUSION: To optimize patients' experiences with self-injection, healthcare workers should assess each patient's age, sex, upper limb function, and pre-self-injection perceptions as demographic, physical, and psychological barriers.

  2023, Patient preference and adherence, 17, 1551 - 1559, English, International magazine

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• A case report of native vertebral osteomyelitis caused by Cutibacterium modestum.

  Taiji Koyama, Goh Ohji, Masako Nishida, Sho Nishimura, Iku Shirasugi, Kenichiro Ohnuma, Mari Kusuki, Kentaro Iwata

  BACKGROUND: Cutibacterium modestum was named in 2020. C. modestum was previously called Propionibacterium humerusii. Several implant-associated infections caused by Cutibacterium species have been previously reported, but native vertebral osteomyelitis due to these bacteria has rarely been reported. CASE PRESENTATION: A 72-year-old man, who had previously received several nerve block injections for low back pain, was referred to our hospital for deterioration in back pain in the last 1 month. MRI findings were suggestive of L5-S1 vertebral osteomyelitis. Blood cultures and bone biopsy culture revealed the presence of Gram-positive bacilli. The isolate was identified as C. modestum by 16SrRNA gene sequencing. A diagnosis of vertebral osteomyelitis caused by C. modestum was made. Minocycline followed by oral amoxicillin was administered for 3 months. His symptom improved and did not recur after treatment completion. CONCLUSION: A case of vertebral osteomyelitis caused by C. modestum was encountered. Although C. modestum is very similar to C. acnes, it could be accurately identified by 16SrRNA gene sequencing. This case represents the first documented C. modestum infection in humans.

  Apr. 2022, BMC infectious diseases, 22(1) (1), 367 - 367, English, International magazine

  Scientific journal