Ревматоидный артрит Rheumatoid Arthritis
Comparative efficacy and tolerability of 5-Loxin and AflapinAgainst osteoarthritis of the knee: a double blind, randomized, placebo controlled clinical study
жүктеу/скачать 3.28 Mb.
|
Comparative efficacy and tolerability of 5-Loxin and AflapinAgainst osteoarthritis of the knee: a double blind, randomized, placebo controlled clinical study.Sengupta K1, Krishnaraju AV, Vishal AA, Mishra A, Trimurtulu G, Sarma KV, Raychaudhuri SK, Raychaudhuri SP.
Aflapin(®) is a novel synergistic composition derived from Boswellia serrata gum resin (Indian Patent Application No. 2229/CHE/2008). Aflapin is significantly better as an anti-inflammatory agent compared to the Boswellia extracts presently available in the market. A 90-day, double-blind, randomized, placebo-controlled study was conducted to evaluate the comparative efficacy and tolerability of 5-Loxin(®) and Aflapin(®) in the treatment of osteoarthritis (OA) of the knee (Clinical trial registration number: ISRCTN80793440). Sixty OA subjects were included in the study. The subjects received either 100 mg (n=20) of 5-Loxin(®) or 100 mg (n=20) of Aflapin(®) or a placebo (n=20) daily for 90 days. Each patient was evaluated for pain and physical functions by using the standard tools (visual analog scale, Lequesne's Functional Index, and Western Ontario and McMaster Universities Osteoarthritis Index) at the baseline (day 0), and at days 7, 30, 60 and 90. A battery of biochemical parameters in serum, urine and hematological parameters in citrated whole blood were performed to assess the safety of 5-Loxin(®) and Aflapin(®) in OA subjects. Fifty seven subjects completed the study. At the end of the study, both 5-Loxin(®) and Aflapin conferred clinically and statistically significant improvements in pain scores and physical function scores in OA subjects. Interestingly, significant improvements in pain score and functional ability were recorded as early as 7 days after initiation of the study in the treatment group supplemented with 100 mg Aflapin. Corroborating the improvements in pain scores in treatment groups, our in vitro studies provide evidences that Aflapin(®) is capable of inhibiting cartilage degrading enzyme MMP-3 and has the potential to regulate the inflammatory response by inhibiting ICAM-1. Aflapin(®) and 5-Loxin(®) reduce pain and improve physical functions significantly in OA subjects. Aflapin exhibited better efficacy compared to 5-Loxin(®). In comparison with placebo, the safety parameters were almost unchanged in the treatment groups. Hence both 5-Loxin(®) and Aflapin(®) are safe for human consumption. Сравнительное исследование эффективности и переносимости препарата 5-Loxin и AflapinAgainst остеоартроз коленных суставов: двойное слепое, рандомизированное, плацебо-контролируемое клиническое исследование. Aflapin(Benz " - это роман синергетический состав производным от Boswellia serrata смолы резинки (индийский патент № 2229/CHE/2008). Aflapin значительно лучше и как противовоспалительное средство по сравнению с Boswellia экстрактов в настоящее время доступна на рынке. В течение 90 дней, двойное слепое, рандомизированное, плацебо-контролируемое исследование проводилось с целью оценки сравнительной эффективности и переносимости 5-Loxin(Benz " и Aflapin(Benz " в лечении остеоартроза (ОА) коленного сустава (клиническое испытание регистрационный номер: ISRCTN80793440). Шестьдесят ОА предметы были включены в исследование. Участники получали либо 100 мг (n=20) 5-Loxin(Benz " или 100 мг (n=20) Aflapin(Benz", либо плацебо (n=20) ежедневно в течение 90 дней. Каждого пациента оценивалось от боли и физических функций с помощью стандартных средств (визуальной аналоговой шкале, Lequesne функционального индекса, и Университет Западного Онтарио и Макмастер университетов Остеоартрит Index) в базисном (день 0), а в 7 дней, 30, 60 и 90. Аккумулятор биохимических показателей сыворотки крови, мочи и гематологических показателей в citrated цельной крови были выполнены для оценки безопасности 5-Loxin(Benz " и Aflapin(Benz " в ОА предметам. Пятьдесят семь пациенты завершили исследование. В конце исследования, как 5-Loxin(Benz " и Aflapin вручил клинически и статистически значимое улучшение оценки боли и физические функции оценки в ОА предметам. Интересно, что значительные улучшения в боль оценка и функциональные возможности были зафиксированы уже 7 дней после начала исследования в лечении группы, получавшей 100 мг Aflapin. Подтверждая улучшение оценки боли в группах лечения, наши исследования in vitro представить доказательства, что Aflapin(Benz " способен ингибировать хряща унижающих достоинство видов ферментов ММП-3 и имеет потенциал для регулирования воспалительной реакции за счет ингибирования ICAM-1. Aflapin(Benz " и 5-Loxin(Benz " уменьшить боль и улучшить физические функции значительно ОА предметам. Aflapin выставлены лучшую эффективность, по сравнению с 5-Loxin (- Benz". В сравнении с плацебо, параметры безопасности, осталось практически неизменным по группам лечения. Следовательно, и 5-Loxin(Benz " и Aflapin(Benz " являются безопасными для потребления человеком. This is the first clinical study to evaluate the efficacy of Aflapin® in OA subjects. Aflapin is a novel synergistic composition comprising AKBA enriched B. serrata extract and non acidic gum extract of B. serrata. In a battery of preclinical studies designed in in vitro cellular models and in vivo animal models, Aflapin exhibited significantly better anti-inflammatory activities in comparison with 5-Loxin® (Data to be presented in a separate communication). 5-Loxin® is a Boswellia serrata extract standardized to 30% AKBA. Its multidirectional activities related to anti-inflammatory efficacies obtained in appropriate cellular, animal models and in human subjects have established that 5-Loxin® is a potent dietary supplement for the management of inflammatory diseases such as osteoarthritis 14-22. In a series of experiments designed in in vitro cellular and in vivo animal models, Aflapin showed significantly better efficacy in comparison with 5-Loxin®. In addition, Aflapin exhibited better AKBA bioavailability than 5-Loxin® in Wistar rat model. Broad spectrum safety of Aflapin was also established in a battery of acute and sub-acute toxicity studies in rat and rabbits. These findings altogether motivated us to evaluate efficacy of Aflapin in comparison with 5-Loxin® against osteoarthritis in human subjects. In the present 90-day clinical study, we assessed the efficacy and tolerability of Aflapin in comparison with 5-Loxin® in OA subjects. Pain, stiffness of joints, reduced joint movement and physical disability are the major clinical manifestations of OA 1,40,41. Our study demonstrates that Aflapin potentially improves pain, joint stiffness and physical function in OA subjects (Figure Figure22). In order to check improvements in the treatment groups, we compared the data for all parameters between the baseline and day 90. Paired t-test revealed that both treatment groups showed statistically significant improvements in all parameters. Compared to the placebo, 5-Loxin® supplementation for 90 days, significantly reduced VAS, WOMAC-pain, WOMAC-stiffness (Table Table33), which are consistent with our previous observations 22. Whereas, Aflapin supplementation for 90 days, resulted in significant reduction in all pain scores tested in comparison with placebo. These findings suggest that Aflapin has better therapeutic efficacy against OA compared to 5-Loxin®. We observed that, in comparison with baseline, there were downward trends in VAS score and WOMAC scores in the placebo group. We believe that this might be partly attributable to the placebo effect 42,43 manifested while administering the questionnaires to placebo subjects and partly due to the consumption of ibuprofen as rescue medication by more subjects in the placebo group during the study. It is noteworthy that 5-Loxin® possesses significant efficacy in lowering VAS score by 8.09% (P=0.022), WOMAC pain score by 8.68% (0.031) and WOMAC function score by 8.35% (P<0.015) in OA subjects as early as 7 days after the initiation of treatment. In comparison, Aflapin showed significant reduction in all the pain scores assessed including VAS score by 12.8% (P=0.0004), LFI score by 9.17% (P=0.003), WOMAC pain score by 11.78% (P=0.012), WOMAC stiffness score by 18.48% (P=0.012) and WOMAC function score by 10.24% (P=0.005) (Figure Figure22). These findings therefore indicate that 5-Loxin® and Aflapin® confers prompt and significant pain relief, improvement in physical ability and quality of life in OA subjects. However, Aflapin showed better reduction in all the tested pain scores and hence can be considered superior to 5-Loxin®. Pathogenesis of osteoarthritis is a complex process. These include mechano-transduction, the interplay between metalloproteases (MMP3, MMP13), protease inhibitors and cytokines on cartilage degradation and mechanisms of cartilage repair 40,44,45. MMP-3 is over-expressed in OA and cause degeneration of cartilage tissue 44,45. Cytokines act via autocrine and endocrine functions to alter cartilage homeostasis. Interleukin-1 (IL-1) and TNF-α are perhaps the best characterized cytokines for cartilage degradation (46,47). They are synthesized by chondrocytes and FLS. These cytokines act in various ways in the pathogenesis of OA such as inhibition of synthesis of type 2 (articular) cartilage and activation of catabolic metalloproteases including MMP-3 which plays a critical role in cartilage degradation 44,45. A role of synovitis in OA can't be disregarded either. It is a well established clinical observation that pain and swelling in OA improves for months following intra-articular corticosteroid injection. In addition, histologic studies suggest that localized inflammatory changes characterized by foci of inflammatory cells occur in up to 50% of OA patients 48. In this study to find out possible mechanism of actions of Aflapin we carried out in vitro studies to evaluate whether Aflapin can inhibit metalloprotease secretion or influence the inflammatory component of osteoarthritis. We observed: (1) Aflapin inhibits TNFα induced MMP-3 secretion in chondrocytes; (2) Aflapin inhibits TNFα induced expression of ICAM-1 in endothelial cells. Overall, the foregoing data together demonstrates the better ability of Aflapin compared with 5-Loxin® in terms of reducing the pain, improving physical function, quality of life and joint health. Presumably these improvements might occur through down regulation of cartilage degrading enzymes such as MMP-3 in OA subjects. The present study also demonstrates no major changes in the hematological parameters, serum biochemical parameters and in urine analysis in the treatment groups compared to placebo. In addition, no major adverse effect was reported by the subjects in the treatment groups. Taken together, these observations further demonstrate that 5-Loxin® and Aflapin® are potentially safe in the treatment of OA in humans and more specifically Aflapin® is more efficacious in the management of osteoarthritis than 5-Loxin®.
|