Gastrointestinal safety and efficacy of long-term GCSB-5 use in patients with osteoarthritis: A 24-week, multicenter study

J Ethnopharmacol. 2016 Aug 2;189:310-8. doi: 10.1016/j.jep.2016.05.031. Epub 2016 May 16.

open access paper

Ha CW¹, Park YB², Kyung HS³, Han CS⁴, Bae KC⁵, Lim HC⁶, Park SE⁷, Lee MC⁸, Won YY⁹, Lee DC¹⁰, Cho SD¹¹, Kim CW¹², Kim JG¹³, Kang JS¹⁴, Lee JH¹⁵, Choi ES¹⁶, Seon JK¹⁷, Lee WS¹⁸, Bin SI¹⁹.

• ¹Department of Orthopedic Surgery, Stem Cell & Regenerative Medicine Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea. Electronic address: chulwon.ha@gmail.com.
• ²Department of Orthopedic Surgery, Chung-Ang University Hospital, Chung-Ang University College of Medicine, Seoul, South Korea. Electronic address: whybe1122@gmail.com.
• ³Department of Orthopedic Surgery, School of Medicine, Kyungpook National University, Daegu, South Korea. Electronic address: hskyung@knu.ac.kr.
• ⁴Department of Orthopedic Surgery, Kyung Hee University Hospital, Seoul, South Korea. Electronic address: chungsoohan29@gmail.com.
• ⁵Department of Orthopedic Surgery, Keimyung University Dongsan Medical Center, Daegu, South Korea. Electronic address: bkc@dsmc.or.kr.
• ⁶Department of Orthopedic Surgery, Korea University Guro Hospital, Seoul, South Korea. Electronic address: lhc2455@daum.net.
• ⁷Department of Orthopedic Surgery, Dongguk University International Hospital, Seoul, South Korea. Electronic address: pse0518@hotmail.com.
• ⁸Department of Orthopedic Surgery, Seoul National University Hospital, Seoul, South Korea. Electronic address: leemc@snu.ac.kr.
• ⁹Department of Orthopedic Surgery, Ajou University Hospital, Suwon, South Korea. Electronic address: thrtkr@ajou.ac.kr.
• ¹⁰Department of Orthopedic Surgery, BoGang Hospital, Daegu, South Korea. Electronic address: osdclee@naver.com.
• ¹¹Department of Orthopedic Surgery, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, South Korea. Electronic address: sdcho@uuh.ulsan.kr.
• ¹²Department of Orthopedic Surgery, Busan Paik Hospital, Inje University, Busan, South Korea. Electronic address: doctor-bluesea@hanmail.net.
• ¹³Department of Orthopedic Surgery, Konkuk University Medical Center, Seoul, South Korea. Electronic address: boram107@hanmail.net.
• ¹⁴Department of Orthopedic Surgery, Inha University Hospital, Incheon, South Korea. Electronic address: kangjoon@inha.ac.kr.
• ¹⁵Department of Orthopedic Surgery, Jeonbuk National University Medical School, Jeonju, South Korea. Electronic address: Jhlee55@jbnu.ac.kr.
• ¹⁶Department of Orthopedic Surgery, Chungbuk National University Hospital, Cheongju, South Korea. Electronic address: oseschoi@chungbuk.ac.kr.
• ¹⁷Department of Orthopedic Surgery, Chonnam National University Hwasun Hospital, Hwasun, South Korea. Electronic address: seonbell@jnu.ac.kr.
• ¹⁸Department of Orthopedic Surgery, Yonsei University College of Medicine, Seoul, South Korea. Electronic address: wsleeos@yuhs.ac.
• ¹⁹Department of Orthopedic Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea. Electronic address: sibin@amc.seoul.kr.

Abstract

ETHNOPHARMACOLOGY RELEVANCE:

A previous study indicated non-inferiority of GCSB-5 to celecoxib regarding efficacy and safety in treating OA; however, the gastrointestinal (GI) safety data was limited to 12 weeks. Accordingly, a longer term study with a larger number of patients was necessary to establish the GI safety of GCSB-5.

AIM OF STUDY:

The primary goal was to determine the safety and efficacy of 24-week use of GCSB-5. The secondary goal was to compare the GI safety data of GCSB-5 with that of the previously reported Celecoxib Long-term Arthritis Safety Study (CLASS).

METHOD:

This was a 24-week, multicenter, single-arm phase IV Study for the safety and efficacy of GCSB-5. A total of 761 patients were enrolled and 756 patients received at least one dose of GCSB-5. Among them, 629 patients (82.7%) completed the 24 week follow up. The primary goal was to determine the safety and efficacy of GCSB-5 for 24 weeks. The secondary goal was to compare the GI safety data of GCSB-5 with that of the previously reported Celecoxib Long-term Arthritis Safety Study (CLASS).

RESULTS:

The incidence of GI disorders of GCSB-5 was 23.7%. The annual rate of perforation, ulcer obstruction, or bleeding (PUB) incidence was 0.0%. The drop-out rate due to GI disorders following GCSB-5 use was 4.8%. Compared to celecoxib data from CLASS, the incidence of GI disorders (23.7% vs. 31.4%, p<0.001), annual rate of PUB and gastroduodenal ulcers (0.0% vs 2.2%, p=0.004), and drop-out rate due to GI disorders following GCSB-5 use were significantly low (4.8% vs 8.7%, p<0.001). Efficacy was proven by significant improvements in Western Ontario McMaster Questionnaire (WOMAC) scale, Korean Knee Score (KKS), 100-mm pain visual analogue scale (VAS), and physician's global assessments of patient's response to therapy (PGART).

CONCLUSIONS:

The safety and efficacy profile of GCSB-5 are comparable to celecoxib. These results indicate GCSB-5 is safe for a long-term treatment of knee OA patients.

TRIAL REGISTRATION:

ClinicalTrials.gov (NCT01604239).
Copyright © 2016 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

KEYWORDS:

GCSB-5; GI safety; Herbal medicine; Osteoarthritis; Shinbaro