Assessment of comparative pain relief and tolerability of SKI306X compared with celecoxib in patients with rheumatoid arthritis: a 6-week, multicenter, randomized, double-blind, double-dummy, phase III, noninferiority clinical trial.
BACKGROUND
SKI306X, which consists of biologically active ingredients from Clematis mandsburica, Tricbosantbes kirilowii, and Prunella vulgaris, was developed and tested in preclinical trials in Korea. Those studies found that SKI306X was associated with an anti-inflammatory and analgesic effect, and that it can delay the destruction of cartilage in rheumatoid arthritis (RA).


OBJECTIVE
The aim of this study was to compare the pain relief and tolerability of SKI306X and celecoxib in patients with RA.


METHODS
This study was a 6-week, multicenter, randomized, double-blind, double-dummy, Phase III, noninferiority clinical trial. Eligible patients were aged 18 to 80 years, had a history of RA with a disease duration of > or =3 months, and were functional American College of Rheumatology (ACR) class I, II, or III before entry. After a washout period of 2 weeks, patients were randomized to SKI306X 200 mg TID or celecoxib 200 mg BID for 6 weeks. The primary end point was a change in patient assessment of pain intensity using a visual analog scale (VAS). The secondary end points were a 20% improvement in response rate as defined by the ACR (ACR20) and the frequency of rescue medication use. Results after 3 and 6 weeks of treatment were compared with baseline and between treatment groups, and all patients were assessed for adverse events (AEs), clinical laboratory data, and vital signs. AEs were identified based on spontaneous reports by patients during interviews conducted by the investigators and the study coordinator.


RESULTS
Two hundred twenty-two Korean patients from 7 medical centers were assessed and 183 were enrolled and randomized to 1 of 2 treatment groups. Ninety-one patients (10 male, 81 female; mean [SD] age, 52.13 [12.64] years; mean [SD] duration of RA, 9.08 [10.23] years; no. [%] of ACR class I, II, and III, 13 [14.29], 44 [48.35] and 34 [37.36] patients, respectively) received SKI306X 200 mg TID and 92 patients (10 male, 82 female; mean [SD] age, 51.78 [10.94] years; mean [SD] duration of RA, 8.78 [7.78] years; no. [%] of ACR class I, II, and III, 14 [15.22], 44 [47.83], and 34 [36.96] patients, respectively) received celecoxib 200 mg BID. An analysis of the change in reported pain intensity as determined by VAS (mm) score between baseline and week 3 (mean [SD], 13.64 [16.62] vs 14.45 [15.89]), and between baseline and week 6 (18.4 [20.8] vs 17.9 [19.1], respectively) suggested that SKI306X was not inferior to celecoxib. The number of patients who achieved ACR20 response rate was not significantly different between the SKI306X group and the celecoxib group at week 3 (16/87 [18.4%] vs 24/87 [27.6%], respectively) and at week 6 (29/87 [33.3%] vs 29/87 [33.3%]). The frequency of rescue medication use was not significantly different between the SKI306X group and celecoxib group at week 3 (54/87 [62.1%] vs 47/87 [54.0%], respectively) or week 6 (57/87 [65.5%] vs 49/87 [56.3%]). Drug-related AEs were reported by 27 (29.7%) patients in the SKI306X group and 22 (23.9%) patients in the celecoxib group. The most frequent drug-related AEs were epigastric pain (9/91 [9.9%]) in the SKI306X group and glutamyltranferase elevation (4/92 [4.3%]) in the celecoxib group. No significant between-group differences were observed in the prevalence of drug-related clinical- or laboratory-determined AEs.


CONCLUSIONS
The results of this study suggest that SKI306X was generally well tolerated and not inferior to celecoxib in regard to pain relief in these Korean patients with RA.
Song
Yeong Wook
YW
Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea. Electronic address: ysong@snu.ac.kr.
Lee
Eun Young
EY
Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.
Koh
Eun-Mi
EM
Department of Internal Medicine, Samsung Medical Center, Seoul, Korea.
Cha
Hoon-Suk
HS
Department of Internal Medicine, Samsung Medical Center, Seoul, Korea.
Yoo
Bin
B
Department of Internal Medicine, Asan Medical Center, Seoul, Korea.
Lee
Chang-Keun
CK
Department of Internal Medicine, Asan Medical Center, Seoul, Korea.
Baek
Han Joo
HJ
Department of Internal Medicine, Gachon Medical School, Gil Medical Center, Incheon, Korea.
Kim
Hyun Ah
HA
Department of Internal Medicine, Hallym University Sacred Heart Hospital, Pyengchon, Korea.
Suh
Young
Y
Department of Internal Medicine, Hallym University Sacred Heart Hospital, Pyengchon, Korea.
Kang
Seong-Wook
SW
Department of Internal Medicine, Chungnam National University Hospital, Daejoen, Korea.
Lee
Yun Jong
YJ
Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.
Jung
Hyung-Gi
HG
Department of Biostatistics, Seo Kyeong University, Seoul, Korea.
D000893:Anti-Inflammatory Agents; D018501:Antirheumatic Agents / Q000009:adverse effects* / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000150:complications / Q000188:drug therapy*; D000068579:Celecoxib; D039324:Clematis; D052246:Cyclooxygenase 2 Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use*; D004311:Double-Blind Method; D004365:Drugs, Chinese Herbal / Q000009:adverse effects* / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007723:Korea; D008297:Male; D008875:Middle Aged; D010146:Pain / Q000188:drug therapy* / Q000209:etiology; D010147:Pain Measurement; D008517:Phytotherapy; D011239:Prednisolone / Q000008:administration & dosage / Q000627:therapeutic use; D031347:Prunella; D011720:Pyrazoles / Q000009:adverse effects* / Q000627:therapeutic use*; D013449:Sulfonamides / Q000009:adverse effects* / Q000627:therapeutic use*
D000893:Anti-Inflammatory Agents; D018501:Antirheumatic Agents; D052246:Cyclooxygenase 2 Inhibitors; D004365:Drugs, Chinese Herbal; D011720:Pyrazoles; C460104:SKI 306X; D013449:Sulfonamides; D011239:Prednisolone; D000068579:Celecoxib