Naohiko Kinoshita

Osaka University of Pharmaceutical Sciences

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Kazuki Kakimoto

Osaka University of Pharmaceutical Sciences

Shirô Nakamura

Kansai Medical University

Takako Miyazaki

Osaka University of Pharmaceutical Sciences

Yuki Hirata

Jichi Medical University

Keijiro Numa

Osaka University of Pharmaceutical Sciences

Hiroki Nishikawa

Osaka University of Pharmaceutical Sciences

Kei Nakazawa

Okayama University

Ryoji Koshiba

Osaka University of Pharmaceutical Sciences

Noboru Mizuta

Osaka University of Pharmaceutical Sciences

Ota K

Osaka University of Pharmaceutical Sciences

Cooperative Institutions

Osaka University of Pharmaceutical Sciences

Osaka Medical and Pharmaceutical University

ProQuest (United States)

National Institute of Diabetes and Digestive and Kidney Diseases

The University of Tokyo

Nara Prefecture General Medical Center

Chikamori Hospital

The Japanese Society of Gastroenterological Surgery

Hyogo Medical University

Showa University

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Efficacy of Switching to Adalimumab for Maintenance of Remission Following Induction Therapy with Tacrolimus in Patients with Ulcerative Colitis

Journal of Clinical Medicine (2023)

Keijiro Numa Kazuki Kakimoto Yasuyoshi Tanaka Noboru Mizuta Naohiko Kinoshita

Tacrolimus (TAC) effectively induces remission in refractory ulcerative colitis (UC). However, TAC therapy usually lasts for 3 months. Although azathioprine (AZA) is often used in maintenance therapy, the relapse rate remains high. Herein, we evaluated the efficacy of adalimumab (ADA) for remission maintenance in patients with UC after induction therapy with TAC.We prospectively enrolled patients with moderate-to-severe UC who achieved clinical remission after 3 months of TAC therapy with endoscopic non-mucosal healing (Cohort A). After TAC discontinuation, the remission maintenance rate up to 1 year after starting ADA therapy was examined. We retrospectively enrolled patients with UC treated with TAC (Cohort B). Among patients in clinical remission after TAC treatment for 3 months, those who received AZA as remission maintenance therapy after TAC discontinuation constituted the AZA group. Patients in Cohort A who received ADA and AZA as remission maintenance therapy after TAC discontinuation constituted the ADA + AZA group. We compared the remission maintenance rates in the AZA and ADA + AZA groups for up to 5 years after TAC discontinuation.In Cohort A, of the 46 patients with UC treated with TAC, 17 were eligible for analysis after receiving ADA as remission maintenance therapy. A notable 88.2% (15/17) were still in remission 1 year after starting ADA. The ADA + AZA group (n = 16) exhibited a significantly higher relapse-free rate than the AZA group (n = 26) (p < 0.05; log-rank test).switching to ADA for remission maintenance in patients with refractory UC who achieved clinical remission with TAC is clinically useful.

Discontinuation

Maintenance therapy

Refractory (planetary science)

10.3390/jcm12206699

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Serum IL-13 Predicts Response to Golimumab in Bio-Naïve Ulcerative Colitis

Journal of Clinical Medicine (2022)

Naohiko Kinoshita Kazuki Kakimoto Hikaru Shimizu Kohji Nishida Keijiro Numa

A certain number of patients with ulcerative colitis (UC) are refractory to anti-TNF-α antibodies; biomarkers are thus needed to predict treatment efficacy. This study aimed to evaluate whether serum biomarkers that were reported to be associated with UC or anti-TNF-α antibody could predict the response to golimumab, a human anti-TNF-α monoclonal antibody, in bio-naïve patients with UC. We prospectively enrolled 23 consecutive patients with UC who were treated with golimumab. Serum samples were collected before the first golimumab dose. Eleven molecules were measured by electrochemiluminescence (ECL) or enzyme-linked immunosorbent assay (ELISA) and their association with efficacy after 10 weeks of golimumab treatment. Among the serum biomarkers, IL-13 levels were significantly higher in the non-remission group than in the remission group (p = 0.014). IL-15 levels were significantly lower in the non-response group than in the response group (p = 0.04). For clinical remission at week 10, the IL-13 0.20 concentration of pg/mL was associated with a sensitivity and specificity of 82.4% and 83.3%, respectively. Serum IL-13 may be a biomarker to predict golimumab efficacy in biologic-naïve patients with UC, and thus may help to tailor personalized treatment strategies.

Golimumab

10.3390/jcm11174952

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Citations (2)

C-Reactive Protein-To-Lymphocyte Ratio Is a Novel Biomarker for Predicting the Long-Term Efficacy of Ustekinumab Treatment in Ulcerative Colitis

Ryoji Koshiba Kazuki Kakimoto Noboru Mizuta Keijiro Numa Naohiko Kinoshita

Ustekinumab, a new anti-interleukin-12/23 antibody, is an effective treatment for ulcerative colitis; however, data regarding predictive factors of its efficacy are limited. This study aimed to identify biomarkers that can predict the long-term outcome of ustekinumab treatment. We retrospectively reviewed the records of patients with active ulcerative colitis treated with ustekinumab at our hospital from June 2020 to January 2023. We divided patients into non-remission and remission groups, and examined whether baseline biomarkers, including C-reactive protein-to-lymphocyte ratio, and early treatment response could predict clinical remission at week 48 of ustekinumab treatment. Of the 33 patients included in the study, 21 (63.6%) were in clinical remission at week 48 of ustekinumab treatment. The baseline C-reactive protein-to-lymphocyte ratio value was identified as an independent prognostic factor for clinical remission at week 48 (odds ratio: 10, 95% confidence interval: 1.6–62.4, p=0.014), with the cutoff value of 3.353 showing excellent prognostic performance (sensitivity: 71.4%, specificity: 83.3%). Furthermore, the clinical response at week 4 (p=0.009) and that at week 8 (p=0.005) were significantly associated with clinical remission at week 48. The baseline C-reactive protein-to-lymphocyte ratio value and early treatment response are useful biomarkers to predict the long-term efficacy of ustekinumab treatment.

Ustekinumab

Vedolizumab

10.20944/preprints202309.0474.v1

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Correction: Tatsumi et al. Biomarkers for Monitoring of Changes in Disease Activity in Ulcerative Colitis. J. Clin. Med. 2023, 12, 7165

Journal of Clinical Medicine (2024)

Yoshihiro Tatsumi Kazuki Kakimoto Azusa Hara Noboru Mizuta Keijiro Numa

Text Correction [...]

10.3390/jcm13133923

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Therapeutic Drug Monitoring of Golimumab for the Prediction of Long-Term Clinical Remission in Patients with Ulcerative Colitis

Digestion (2022)

Hideki Tawa Kazuki Kakimoto Keijiro Numa Naohiko Kinoshita Yuka Kawasaki

A considerable number of patients with ulcerative colitis (UC) who initially respond to golimumab (GLM), an anti-TNF-α antibody, gradually lose clinical response. Therapeutic drug monitoring has been proposed to optimize serum anti-TNF-α antibody concentrations before the loss of response; however, little is known about ideal serum GLM concentrations. We aimed to evaluate whether the serum GLM trough levels (TLs) early after the initiation of induction therapy affect the long-term outcomes in UC and to identify the early GLM TLs that should be targeted for better long-term outcomes.Thirty-one patients were prospectively evaluated. The primary outcome was clinical remission at 54 weeks, and we measured the serum GLM TLs at weeks 6, 10, and 14. Receiver operating characteristic (ROC) curves were constructed to identify optimal GLM TL thresholds early after induction therapy that were associated with clinical remission at week 54.The GLM TL at week 14, but not at weeks 6 or 10, was significantly associated with clinical remission at week 54 (median [IQR] 1.6 [1.3-1.6] μg/mL vs. 0.9 [0.6-1.3] μg/mL; p = 0.04). The area under the ROC curve for GLM TLs at week 14 was 0.78. We identified a week-14 GLM TL of 1.1 μg/mL as the target threshold for achieving clinical remission at week 54.Our results demonstrate the value of early serum GLM TLs in predicting the long-term outcomes of GLM for patients with UC.

Golimumab

Therapeutic Drug Monitoring

10.1159/000524593

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C-reactive protein-to-lymphocyte ratio is a novel biomarker for predicting the long-term efficacy of ustekinumab treatment in ulcerative colitis

PLoS ONE (2024)

Ryoji Koshiba Kazuki Kakimoto Noboru Mizuta Keijiro Numa Naohiko Kinoshita

Ustekinumab, a new anti-interleukin-12/23 antibody, is an effective treatment for ulcerative colitis; however, data regarding predictive factors of its efficacy are limited. Predicting treatment efficacy in advance would be useful for selecting a therapeutic agent. This study aimed to identify biomarkers that can predict the long-term outcome of ustekinumab treatment.

Ustekinumab

10.1371/journal.pone.0305324

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Biomarkers for Monitoring of Changes in Disease Activity in Ulcerative Colitis

Journal of Clinical Medicine (2023)

Yoshihiro Tatsumi Kazuki Kakimoto Azusa Hara Noboru Mizuta Keijiro Numa

Background: In recent years, various biomarkers of ulcerative colitis (UC) have emerged; however, few studies have simultaneously examined the utility of multiple biomarkers for monitoring disease activity. Additionally, serum leucine-rich alpha-2 glycoprotein (LRG), a new biomarker, may show a blunt response to anti-TNF antibody therapy. This prospective study explored effective biomarkers that could monitor disease activity changes in patients with UC. In addition, we examined the effect of anti-TNF antibody therapy on changes in LRG. Methods: Blood and stool samples were collected twice from patients with UC: at baseline and at least 8 weeks later. Changes in serum LRG, interleukin (IL)-6, prealbumin (pre-Alb), high-sensitivity C-reactive protein (hs-CRP), CRP, and fecal calprotectin (FC) were measured and correlated with changes in disease activity. The relationship between anti-TNF antibody therapy and LRG levels was also examined in patients with the same disease activity. Results: Forty-eight patients with UC (96 samples) were analyzed. ΔLRG and ΔIL-6 correlated strongly with the change in the partial Mayo (pMayo) score between the two time points (ΔpMayo) (r = 0.686, 0.635, respectively). In contrast, FC and IL-6 were particularly accurate predictors of clinical remission, and their area under the curves (AUCs) were significantly higher than that of CRP (AUC: 0.81, 0.76 vs. 0.50; p = 0.001, 0.005). No association was found between the administration of anti-TNF antibody preparations and the LRG values. Conclusions: Correlations were found between changes in UC disease activity and LRG, IL-6, pre-Alb, hs-CRP, CRP, and FC. LRG reflects disease activity during anti-TNF antibody therapy.

10.3390/jcm12227165

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Citations (8)

Efficacy of Switching to Adalimumab for Maintenance of Remission Following Induction Therapy with Tacrolimus in Patients with Ulcerative Colitis

Keijiro Numa Kazuki Kakimoto Yasuyoshi Tanaka Noboru Mizuta Naohiko Kinoshita

Background: Tacrolimus (TAC) effectively induces remission in refractory ulcerative colitis (UC). However, TAC therapy usually lasts for 3 months. Although azathioprine (AZA) is often used in maintenance therapy, the relapse rate remains high. Herein, we evaluated the efficacy of adalimumab (ADA) for remission maintenance in patients with UC after induction therapy with TAC. Methods: We prospectively enrolled patients with moderate-to-severe UC who achieved clinical remission after 3 months of TAC therapy with endoscopic non-mucosal healing (Cohort A). After TAC discontinuation, the remission maintenance rate for up to 1 year after starting ADA therapy was examined. We retrospectively enrolled patients with UC treated with TAC (Cohort B). Among patients in clinical remission after TAC treatment for 3 months, those who received AZA as remission maintenance therapy after TAC discontinuation constituted the AZA group. Patients in Cohort A who received ADA and AZA as remission maintenance therapy after TAC discontinuation constituted the ADA group. We compared the remission maintenance rates in AZA and ADA groups for up to 5 years after TAC discontinuation. Results: In Cohort A, of the 46 patients with UC treated with TAC, 17 were eligible for analysis after receiving ADA as remission maintenance therapy. A notable 88.2% (15/17) were still in remission 1 year after starting ADA. The ADA group (n=16) exhibited a significantly higher relapse-free rate than the AZA group (n=26) (p<0.05; log-rank test). Conclusion: Switching to ADA for remission maintenance in patients with refractory UC who achieved clinical remission with TAC is clinically useful.

Discontinuation

Maintenance therapy

Refractory (planetary science)

10.20944/preprints202309.1942.v1

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Citations (1)