Content uploaded by Bhushan K Patwardhan
Author content
All content in this area was uploaded by Bhushan K Patwardhan
Content may be subject to copyright.
Randomized double blind trial of an Ayurvedic plant derived formulation for treatment of rheumatoid arthritis
Abstract
To evaluate RA-1, a standardized plant extract formulation, traditionally considered a safe, effective antiarthritic in the Asian-Indian Ayurvedic medicinal system.
One hundred eighty-two patients with active-on-chronic rheumatoid arthritis (RA) participated in a 16 week randomized, double blind, placebo controlled, parallel efficacy clinical drug trial in Pune, India. Tenderness, pain, swelling, and several other efficacy measures were assessed by (1) ACR core set 20% and 50% improvement; (2) ACR 20% improvement response. An intent-to-treat analysis was performed; p<0.05 considered significant.
Seventeen patients withdrew (active = 9; placebo = 8); none withdrew due to drug toxicity. An unprecedented placebo response (often p<0.001 in within-group change) was observed. The active RA-1 group remained numerically superior at all evaluation timepoints. RA-1 demonstrated few significant differences: (1) increased proportion with 50% reduction in swollen joint count (95% CI approximately 1.52, 29.90) and swollen joint score (95% CI approximately 0.91, 28.73); (2) reduced rheumatoid factor (95% CI approximately -303.7, -2.72); 39% in the RA-1 group versus 30% placebo showed ACR 20% improvement (95% CI approximately -5.48, 24.59). Only minor side effects were seen, with no significant differences by treatment group.
In a trial with sufficient power, RA-1 revealed efficacy that was not significantly superior to the strong placebo response, except for improvement in joint swelling. Further, the effect on RF and good safety profile led to an open label phase.
... includes inhibition of microsomal prostaglandin E2 synthase-1 (PGE2) and 5-lipoxygenase, reducing the production or activation of inflammatory mediators such as matrix metalloproteinase (MMP)-9, MMP-13, cyclooxygenase (COX)-2, and nitric oxide (NO) and also has analgesic and anti-arthritic effects [104,105]. It has been found to reduce the number of osteophytes by attenuating inflammatory mediators such as C-reactive protein and hyaluronic acid [111][112][113]. Research by scientists has demonstrated the safety of using Boswellia serrata R. [112]. ...
Rheumatoid arthritis refers to joint diseases of unclear etiology whose final stages can lead to unbearable pain and complete immobility of the affected joints. As one of the most widely known diseases of the joints, it serves as a study target for a large number of research groups and pharmaceutical companies. Modern treatment with anti-inflammatory drugs, including janus kinase (JAK) inhibitors, monoclonal antibodies, and botanicals (polyphenols, glycosides, alkaloids, etc.) has achieved some success and hope for improving the course of the disease. However, existing drugs against RA have a number of side effects which push researchers to elaborate on more selective and effective drug candidates. The avant-garde of research, which aims to develop treatment of rheumatoid arthritis using antisense oligonucleotides along with nonsteroidal drugs and corticosteroids against inflammation, increases the chances of success and expands the arsenal of drugs. The primary goal in the treatment of this disease is to find therapies that allow patients with rheumatoid arthritis to move their joints without pain. The main purpose of this review is to show the victories and challenges for the treatment of rheumatoid arthritis and the tortuous but promising path of research that aims to help patients experience the joy of freely moving joints without pain.
... However, the contribution of most of them to anti-arthritic activities should be further uncovered; 60 percent of those who suffer from rheumatoid arthritis look for herbal remedies [39]. According to Chopra et al., when it comes to establishing the legitimacy of traditional herbal medicines on a global scale, more rigorous studies are necessary to determine their efficacy and safety [40]. The main goal of our study was to find new molecules from NAT that showed promise and could be used to treat arthritis with few side effects. ...
Rheumatoid arthritis (RA) is an autoimmune disease characterized by bone and joint degeneration. Existing anti-inflammatory chemotherapy drugs offer temporary relief but come with undesirable side effects. Herbal medications have shown positive effects on RA symptoms with minimal adverse reactions. In this study, we investigated the potential of Nyctanthes arbor-tristis (NAT) through in vitro and in silico research. Hydroethanolic extracts of harsingar were prepared using the reflux method, containing alkaloids, phenol, saponin, steroids, proteins, tannins, terpenoids, carbohydrates, glycosides, and flavonoids, which exhibited TPC (98.56 ± 0.46 mg GAE/g) and TFC (34.51 ± 0.45 mg CE/g). LC–MS/MS analyzes the active compounds in the extract. NAT exhibited the best scavenging capabilities at 1 mg/mL in anti-oxidant and anti-arthritic activity. Maximum splenocyte proliferation occurred at 250 µg/mL. In vitro cell splenocyte studies revealed the downregulation of TNF-α and the upregulation of IL-10. Additionally, an in silico study demonstrated that bioactive constituents and targets bind with favorable binding affinity. These findings demonstrate the potential of Nyctanthes arbor-tristis in exerting anti-arthritic effects, as supported by in vitro and in silico studies. Further mechanistic research is necessary to validate the therapeutic potential of all phytoconstituents in RA treatment.
... The secondary outcome of the study consisted of a change in the WOMAC subscale of pain (WOMAC-P; scale of 0-4; averaged response of 5 questions), stiffness (WOMAC-S; scale of 0-4; averaged response for 2 questions), and physical function (WOMAC-PF; scale of 0-4; averaged response for 17 questions) at the end of week 4, 8, and 12 from baseline [20]. Other measures performed included health-related quality of life as evaluated by a validated EQ-5D-5L questionnaire consisting of 5 domains -mobility, self-care, usual activities, pain/ discomfort, and anxiety/depression using 5 response levels -no problems, slight problems, moderate problems, severe problems, and extreme problems [21]. ...
Purpose:
Knee osteoarthritis (OA) is the most common form of clinical arthritis in middle-aged and older individuals. Undenatured or native type II (TII) collagen derived from the chicken sternum has a good therapeutic effect on relieving severe pain of OA. Hence, the present study aimed to investigate the efficacy and safety of TII collagen (Native CT-II®) in individuals with knee OA.
Methods:
We conducted a 12-week randomised, double-blind, placebo-controlled, parallel-group study on 101 participants aged 40-65 years with knee OA. The participants were randomised to receive either TII collagen, glucosamine hydrochloride + chondroitin sulfate (G + C) or a placebo. The primary outcome was an improvement in the joint health of the participants assessed using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) compared to G + C and placebo.
Results:
Compared with the placebo group (n = 27), the TII collagen group (n = 29) and G + C group (n = 29) significantly improved the overall joint health measured by the change in WOMAC total score (week 12: TII collagen = -32.47 ± 19.51 and G + C = -33.74 ± 24.64 vs. placebo = -13.84 ± 17.61; p < 0.05) and relieved knee joint pain (week 12: TII collagen = -5.69 ± 3.66 and G + C = -6.03 ± 4.72 vs. placebo = -2.71 ± 3.95; p < 0.05). The statistically significant effect was observed as early as 4 weeks after the investigational product administration. Additionally, the TII collagen was more effective in improving the quality of life than the G + C.
Conclusion:
TII collagen not only has a significantly better effect and high safety profile for OA but also improves the quality of life of patients.
Level of evidence:
Level 1 - Randomized Controlled Trial.
Trial registration:
ClinicalTrials.gov Identifier: NCT04470336 ; First submitted date: July 08, 2020; First posted date: July 14, 2020.
... Wight & Arn., Boerhaavia diffusa L., Plumbago zeylanica L., Terminalia chebula Retz., Withania somnifera Dunal, Vitex negundo L., Vanda roxburghii R. Br., Solanum nigrum L., Tinospora cordifolia Miers ex Hook f. & Thoms., Piper longum L., Cyperus scariosus R. Br., and Embelia ribes Burm. F. [21][22][23][24][25] . ...
... Wight & Arn., Boerhaavia diffusa L., Plumbago zeylanica L., Terminalia chebula Retz., Withania somnifera Dunal, Vitex negundo L., Vanda roxburghii R. Br., Solanum nigrum L., Tinospora cordifolia Miers ex Hook f. & Thoms., Piper longum L., Cyperus scariosus R. Br., and Embelia ribes Burm. F. [21][22][23][24][25] . ...
... Boswellia combination with Curcuma longa, Zingiber officinale, and Withania somnifera Treatment with the combination of Boswellia serrata, Curcuma longa, Zingiber officinale, and Withania somnifera resulted in a substantial reduction in disability and pain severity [142,143] 22. Crude methanolic extract and the pure compound A pure compound from BS extract exhibited anti-inflammatory properties in human PBMCs and mouse macrophages through inhibition of TNFα, IL-1β, NO, [47] (continued) ...
This review explores the convergence of traditional wisdom and modern science in the realm of herbal medicines, focusing on the safety, efficacy, and bioactivity of these natural remedies in contemporary healthcare. The rich history of herbal medicines, deeply embedded in cultural traditions, is witnessing a resurgence as the quest for holistic and personalized healthcare gains momentum. Herbal medicine, a time-honored practice passed down through generations, is experiencing renewed interest amid the growing acknowledgment of its potential benefits. This review delves into the safety profiles of herbal remedies, subjecting them to rigorous scientific scrutiny. Additionally, it investigates the efficacy of herbal interventions, aiming to bridge the gap between historical anecdotes and empirical research. The complex bioactivity of herbal compounds, often containing numerous active ingredients, is a focal point, unraveling the mechanisms through which these natural substances interact with the human body. In a world where the synthesis of traditional wisdom and modern science holds promise for advancing healthcare, this review contributes to the ongoing dialogue. By critically examining the safety, efficacy, and bioactivity of herbal remedies, it aims to illuminate the evolving landscape of herbal medicine. The goal is to integrate the best of both worlds to enhance global well-being, acknowledging the potential of herbal medicine as a valuable complement to modern healthcare practices.
The Indian traditional system of conventional medication includes an enormous lexis of herbal preparations and medicinal plants. They are optional nutrients that are mostly produced by plants as a form of defence. These items may include isolated nutrients, nutritional supplements, particular diets, herbal products, processed foods, and drinks. They may also include genetically modified designer foods. Phytochemicals are naturally occurring compounds that can be found in a variety of foods, including legumes, fruits, vegetables, whole grains, and herbs. These substances include polyphenols, flavonoids, isoflavonoids, anthocyanidins, phytoestrogens, terpenoids, carotenoids, limonoids, phytosterols, glucosinolates, and fibers. Phytochemicals are known to have a significant impact on human health, with potential medical benefits that can help prevent and treat a range of illnesses and physiological abnormalities. Phytochemicals have been shown to have various pharmacological effects on human health, including acting as powerful antioxidants, antibacterial and antifungal agents, anti-inflammatory and anti-allergic compounds, antispasmodic agents, chemo preventive agents, hepatoprotective agents, neuroprotective agents, as well as hypolipidemic and hypotensive agents. Therefore, these compounds are of great interest in the fields of medicine, nutrition, and health science. They also induce apoptosis, act as a diuretic, stimulate the central nervous system, modulate the immune response, and act as a carminative, analgesic. It is necessary for herbal products to undergo quality control, thorough testing to determine their efficacy and safety, and reliable clinical trials. To give improved health care services to the public, the meticulous and scientific integration of India's traditional system of herbal medicine into evidence-based clinical illness management is crucial. Thus, this chapter focuses on the integration and advancement of herbal-based medicines through the scientific validation of some clinically important bioactive phytochemicals.
Zusammenfassung
Methoden der komplementären und alternativen Medizin („complementary and alternative medicine“ [CAM]) stoßen bei vielen Patienten mit rheumatischen Erkrankungen auf Interesse. Die wissenschaftliche Datenlage ist durch eine große Anzahl von Publikationen bei einem eklatanten Mangel an verwertbaren klinischen Studien gekennzeichnet. Anwendungen der CAM stehen im Spannungsfeld zwischen dem Bemühen um eine evidenzbasierte Medizin und um qualitativ hochwertige Therapiekonzepte auf der einen und wenig fundierten bis eindeutig unseriösen Angeboten auf der anderen Seite. Die Deutsche Gesellschaft für Rheumatologie (DGRh) hat 2021 eine Kommission Komplementäre Heilverfahren und Ernährung ins Leben gerufen, welche die aktuelle Evidenz für CAM-Anwendungen und ernährungsmedizinische Maßnahmen in der Rheumatologie sichten und in praktisch anwendbare Empfehlungen einarbeiten soll. Für die vorliegende Publikation wurden für 4 Bereiche Empfehlungen für den rheumatologischen Praxisalltag erstellt: Ernährung, mediterrane Kost, ayurvedische Medizin und Homöopathie.
A study was conducted to develop criteria for clinical remission in rheumatoid arthritis (RA). Data were provided by 35 rheumatologists on 175 RA patients considered to be in complete remission (with or without antirheumatic therapy) and 169 RA patients in partial remission or with active disease. Six criteria yielded optimal discrimination: morning stiffness absent or not exceeding 15 minutes, no fatigue, no joint pain by history, no joint tenderness, no joint or tendon sheath swelling, and no elevation of erythrocyte sedimentation rate. In this study sample, the presence of five or more of these criteria in an individual patient yielded 72% sensitivity for clinical remission and 100% specificity in discriminating RA patients with active disease. In a population sample, it is estimated that the overall accuracy of these criteria would be more than 90% in RA patients.
The revised criteria for the classification of rheumatoid arthritis (RA) were formulated from a computerized analysis of 262 contemporary, consecutively studied patients with RA and 262 control subjects with rheumatic diseases other than RA (non-RA). The new criteria are as follows: 1) morning stiffness in and around joints lasting at least 1 hour before maximal improvement; 2) soft tissue swelling (arthritis) of 3 or more joint areas observed by a physician; 3) swelling (arthritis) of the proximal interphalangeal, metacarpophalangeal, or wrist joints; 4) symmetric swelling (arthritis); 5) rheumatoid nodules; 6) the presence of rheumatoid factor; and 7) radiographic erosions and/or periarticular osteopenia in hand and/or wrist joints. Criteria 1 through 4 must have been present for at least 6 weeks. Rheumatoid arthritis is defined by the presence of 4 or more criteria, and no further qualifications (classic, definite, or probable) or list of exclusions are required. In addition, a “classification tree” schema is presented which performs equally as well as the traditional (4 of 7) format. The new criteria demonstrated 91–94% sensitivity and 89% specificity for RA when compared with non-RA rheumatic disease control subjects.
Objective. To develop a set of disease activity measures for use in rheumatoid arthritis (RA) clinical trials, as well as to recommend specific methods for assessing each outcome measure. This is not intended to be a restrictive list, but rather, a core set of measures that should be included in all trials.
Methods. We evaluated disease activity measures commonly used in RA trials, to determine which measures best met each of 5 types of validity: construct, face, content, criterion, and discriminant. The evaluation consisted of an initial structured review of the literature on the validity of measures, with an analysis of data obtained from clinical trials to fill in gaps in this literature. A committee of experts in clinical trials, health services research, and biostatistics reviewed the validity data. A nominal group process method was used to reach consensus on a core set of disease activity measures. This set was then reviewed and finalized at an international conference on outcome measures for RA clinical trials. The committee also selected specific ways to assess each outcome.
Results. The core set of disease activity measures consists of a tender joint count, swollen joint count, patient's assessment of pain, patient's and physician's global assessments of disease activity, patient's assessment of physical function, and laboratory evaluation of 1 acute-phase reactant. Together, these measures sample the broad range of improvement in RA (have content validity), and all are at least moderately sensitive to change (have discriminant validity). Many of them predict other important long-term outcomes in RA, including physical disability, radiographic damage, and death. Other disease activity measures frequently used in clinical trials were not chosen for any one of several reasons, including insensitivity to change or duplication of information provided by one of the core measures (e.g., tender joint score and tender joint count) The committee also proposes specific ways of measuring each outcome.
Conclusion. We propose a core set of outcome measures for RA clinical trials. We hope this will decrease the number of outcomes assessed and standardize outcomes assessments. Further, we hope that these measures will be found useful in long-term studies.
One hundred eighty-six patients with active rheumatoid arthritis were evaluated in a double-blind, randomized study that compared treatment with sulfasalazine (SSZ) (2 gm/day), gold sodium thiomalate (GST) (50 mg/week), and placebo (PBO). The 37—week course of therapy was completed by 109 patients. While marked improvement was seen in all 3 treatment groups, the only statistically significant differences between SSZ or GST and PBO were in a decreased erythrocyte sedimentation rate and increased grip strength in the right hand. GST is known to be superior to PBO, and the response of the GST-treated group was similar to that seen in other trials. The response of the PBO group, however, was much greater than in other placebo groups we have studied. SSZ was similar in efficacy to injectable gold, but was better tolerated. Because of adverse drug reactions (most commonly, rash, stomatitis, and proteinuria), 41% of patients were withdrawn from the GST treatment. Untoward drug effects (most frequently, rash and gastrointestinal distress) caused 16% of patients to be withdrawn from SSZ therapy.
Objective. Trials of rheumatoid arthritis (RA) treatments report the average response in multiple outcome measures for treated patients. It is more clinically relevant to test whether individual patients improve with treatment, and this identifies a single primary efficacy measure. Multiple definitions of improvement are currently in use in different trials. The goal of this study was to promulgate a single definition for use in RA trials.
Methods. Using the American College of Rheumatology (ACR) core set of outcome measures for RA trials, we tested 40 different definitions of improvement, using a 3-step process. First, we performed a survey of rheumatologists, using actual patient cases from trials, to evaluate which definitions corresponded best to rheumatologists' impressions of improvement, eliminating most candidate definitions of improvement. Second, we tested 20 remaining definitions to determine which maximally discriminated effective treatment from placebo treatment and also minimized placebo response rates. With 8 candidate definitions of improvement remaining, we tested to see which were easiest to use and were best in accord with rheumatologists' impressions of improvement.
Results. The following definition of improvement was selected: 20% improvement in tender and swollen joint counts and 20% improvement in 3 of the 5 remaining ACR core set measures: patient and physician global assessments, pain, disability, and an acutephase reactant. Additional validation of this definition was carried out in a comparative trial, and the results suggest that the definition is statistically powerful and does not identify a large percentage of placebo-treated patients as being improved.
Conclusion. We present a definition of improvement which we hope will be used widely in RA trials.
Evaluation of polyarthritis in 110 patients in civilian and armed force life revealed 89 with rheumatoid arthritis (RA). In
the Indian population, RA seems milder and confined to the joints. A substantial number of male patients appeared to share
features with spondarthritis, often in HLA-B27 positive individuals.
In this article the relationship between the cellular elements of the immune response and inflammation are examined with reference to the B lymphocyte repertoire. Evidence is presented that, in addition to an environment in the joint that favors localization and activation of auto-reactive B lymphocytes, the circulating B lymphocyte pool in rheumatoid arthritis is abnormally enriched in cells that bear a receptor for mouse erythrocytes and possess CD5 antigen. B lymphocytes with these novel phenotypic markers secrete autoantibodies and are found in abundance in fetal lymphoid tissues and cord blood; analogous cells in the mouse belong to a distinct lineage and are implicated in allotype- and idiotype-restricted interactions. It is postulated that a subset of B lymphocytes is of primary importance in the etiopathogenesis of rheumatoid disease.