Results of Discontinuation Rate, Remission Rate, and Improvement in Social Functioning Associated with Atypical Antipsychotic Medications in Patients with Schizophrenia: 52-Week Evaluation of JUMPs, a Randomised, Open-Label, Naturalistic Study in Japan

Background: The Japan Useful Medication Program for Schizophrenia (JUMPs) is the first large-scale, long-term (2 years) naturalistic study to assess effectiveness and safety of aripiprazole, blonanserin, and paliperidone in patients with schizophrenia. Here, we present the 52-week results. Methods: This open-label, three-arm, multicentre, randomised, parallel-group study was conducted at 75 sites in Japan. Outpatients with schizophrenia, age ≥20 years, requiring antipsychotic treatment or switching were randomised (1:1:1) to receive oral aripiprazole, blonanserin, or paliperidone as monotherapy during a 4-week titration period (start of monotherapy). The primary endpoint was treatment discontinuation rate over 52 weeks using Kaplan-Meier analysis. Secondary outcomes included social functioning score (Personal and Social Performance Scale [PSP]; Euro QOL-5 dimensions) and safety over 52 weeks. Findings: A total of 251 patients were randomised (July 2012 to December 2013) to receive aripiprazole (n=82), blonanserin (n=85), and paliperidone (n=84). The mean (SD) age was 46·5 (13·3) years and disease duration was 17·1 (12·3) years; 53% were men. Discontinuation rate over 52 weeks (68·3%, 68·2%, and 65·5%) did not differ significantly in aripiprazole, blonanserin, and paliperidone groups, respectively (log-rank test, p=0·9771). The median (95% confidence interval; interquartile range: quartile (Q)1-Q3) time to treatment discontinuation was 144·5 (91·0‒210·0; 51-not applicable), 144·0 (81·0‒238·0; 56-417), and 129·5 (84·0‒252·0; 54.5-not applicable) days in the aripiprazole, blonanserin, and paliperidone groups, respectively. In comparison to eligibility assessments, significant improvements (all p<0·05) in PSP scores were observed at start of monotherapy, week 26, and week 52 in the overall cohort and blonanserin group and at week 26 in the aripiprazole group. The adverse event profile favoured blonanserin. Interpretation: The treatment discontinuation rate of aripiprazole, blonanserin, and paliperidone was similar in patients with chronic schizophrenia in Japan. Clinical Trial Number: (UMIN Clinical Trials Registry 000007942) Funding Statement: Funding provided by The Waksman Foundation of Japan Inc. Declaration of Interests: J. Ishigooka reports grant from The Waksman Foundation of Japan Inc. for the work under consideration for publication, personal fees from Dainippon Sumitomo, Eisai, Eli Lilly, MSD, Novartis, Otsuka, Pfizer, Shionogi, and Takeda, outside the submitted work. K. Nakagome reports grant from The Waksman Foundation of Japan Inc. during the conduct of this study and from Meiji Seika Pharma, Otsuka pharmaceutical, Sumitomo Dainippon pharma, Mochida pharmaceutical, Janssen pharmaceutical K.K., Mitsubishi Tanabe Pharma, Nippon Boehringer Ingelheim (BI), Astellas pharma, Asahi Kasei pharma and Shionogi and personal fees from Meiji Seika Pharma, MSD K.K., Otsuka pharmaceutical, Kyowa Hakko Kirin, Sumitomo Dainippon pharma, Takeda pharmaceutical, Eli Lilly Japan, K.K., Pfizer Japan, Nippon BI, Toyama Chemical, Mochida pharmaceutical, Janssen pharmaceutical, Page 16 of 30 Yoshitomiyakuhin corporation, Taisho Toyama Pharma, and Kowa, outside the submitted work. T. Ohmori reports personal fees from Astellas, Daiichi Sankyo, Dainippon Sumitomo, Eisai, Eli Lilly, GlaxoSmithKline, Meiji, Mochida, MSD, Novartis, Otsuka, Pfizer, Takeda, Mitsubishi Tanabe, and Yoshitomi, and grants from Astellas, Dainippon Sumitomo, Eisai, Meiji, Otsuka, and Pfizer. N. Iwata reports personal fees from Dainippon Sumitomo, Eli Lilly, Janssen, Otsuka, Meiji, and Pfizer and grant from Otsuka, outside of submitted work. K. Inada reports personal fees from Dainippon Sumitomo, Eisai, Eli Lilly, Janssen, MeijiSeika Pharma, Mochida, MSD, Novartis, Otsuka, Shionogi, Tanabe-Mitsubishi, and Yoshitomi and grant from MSD, outside the submitted work. J. Iga reports personal fees from Dainippon Sumitomo, Eli Lilly, Janssen, Meiji-Seika Pharma, Mochida, MSD, Mylan, Novartis, and Otsuka, outside the submitted work. T. Kishi reports personal fees from Daiichi Sankyo, Dainippon Sumitomo, Eisai, Janssen, Otsuka, Meiji, MSD, Tanabe-Mitsubishi, and Yoshitomi, outside the submitted work and grants from the Health and Labor Sciences and Fujita Health University School of Medicine for the work under consideration for publication. H. Tabuse reports personal fees from Dainippon Sumitomo, Eli Lilly, GlaxoSmithKline, Janssen, Otsuka, Meiji, Pfizer, Tanabe-Mitsubishi, and Yoshitomi, outside the submitted work. Hiroshi Terada reports personal fees from Eli Lilly Japan K.K., Janssen pharmaceuticals K.K., Otsuka, Meiji, Dainippon Sumitomo, Tanabe-Mitsubishi, and Yoshitomiyakuhin, outside the submitted work. Y. Tsutsumi reports personal fees from Otsuka and Janssen, outside the submitted work. Y. Kanda reports personal fees from Eli Lilly Japan K.K. and Janssen pharmaceutical K.K. during the conduct of the study and from Eli Lilly Japan K.K. outside the submitted work. K. Sekiyama reports personal fees from Otsuka, outside the submitted work. K. Fujita, Y. Kikuchi, T. Shichijo, S. Koretsune, Haruko Terada, T. Kishimoto, and K. Ohi have no conflicts of interest. Ethics Approval Statement: The study was approved by the appropriate institutional review boards and was conducted in accordance with the Declaration of Helsinki, the International Conference on Harmonisation Tripartite Guidelines for Good Clinical Practice, and the Ethics Guidelines for Clinical Research (Ministry of Health, Labour and Welfare, 2008 revision). Written informed consent was obtained from all patients.