Adjunct role of potassium-rich vegetarian diet and a novel potassium food supplement to improve pain in chronic rheumatoid arthritis on supervised standard care: a randomised controlled study.

Introduction: An earlier food survey showed dietary potassium deficiency in rheumatoid arthritis (RA). Objective: To evaluate an adjunct role of oral potassium to reduce joint pain in RA. Methods: 172 consenting eligible symptomatic patients (median duration 6.5 years) on standard care were randomised into an assessor blind, parallel efficacy, controlled, prospective, multiarm single-centre study (80% power, drug trial design) of 16 weeks duration-arm A (potassium-rich vegetarian diet), arm B (arm A plus novel potassium food supplement) and arm C (control, regular diet). Standard efficacy (American College of Rheumatology recommendation) and safety and diet intake (3-day recall) were assessed at monthly intervals (protocol). Standard soft-ware package (SPSS V.20) was used for statistical analysis; analysis of variance), Mann-Whitney statistic and χ2 test.; significant p<0.05, two sided). Study arms were found matched at baseline. Background RA medication remained stable. Preset target for increased potassium intake (India standards) were mostly achieved and participants remained normokalemic. Results: 155 patients (90.1%) completed the study and several showed improvement (maximum improved measures in arm B). Potassium intervention was safe and well tolerated. Adverse events were mild; none caused patient withdrawal. On comparison, the mean change in pain visual analogue scale (-2.23, 95% CI -2.99 to -1.48) at week 16 (primary efficacy) from baseline was significantly superior in arm B (per protocol analysis). A high daily potassium intake (5-7.5 g, arm B) was significantly associated with low pain (study completion); OR 2.5 (univariate analysis), likelihood ratio 2.9 (logistic regression). Compliance (intervention), diet record and analysis, RA medication and absence of placebo were potential confounders. Conclusion: High oral potassium intake, based on a suitable vegetarian diet and food supplement, reduced joint pain and improved RA. It was a safe adjunct to standard care, Further validation studies are required. Trial registration: CTRI/2022/03/040726; Clinical Trial Registry of India.

Co-administration of AYUSH 64 as an adjunct to standard of care in mild and moderate COVID-19: A randomized, controlled, multicentric clinical trial.

OBJECTIVE: Evaluate the efficacy of AYUSH 64, a standard polyherbal Ayurvedic drug in COVID-19. METHODS: During the first pandemic wave, 140 consenting and eligible hospitalized adult participants with mild-moderate symptomatic disease (specific standard RT-PCR assay positive) were selected as per a convenience sample, and randomized (1:1 ratio) to an open-label (assessor blind) two-arm multicentric drug trial; standard of care (SOC as per Indian guidelines) versus AYUSH 64 combined with SOC (AYUSH plus). Participants were assessed daily and discharged once clinical recovery (CR, primary efficacy) was achieved which was based on a predetermined set of criteria (resolution of symptoms, normal peripheral oximetry, and negative specific RT-PCR assay). Each participant was followed using an indigenous software program(mobile phone) and completed a 12-week study period. The dose of AYUSH 64 was 2 tablets oral, 500 mg each, bid for 12 weeks (AYUSH plus only). Significant P was <0.05 (two-sided). On randomization, the groups were found well matched. RESULTS: The mean interval time from randomization to CR was significantly superior in the AYUSH plus group [mean 6.45 days versus 8.26 days, 95% Confidence Interval of the difference -3.02 to -0.59 (P = 0.003, Student's 't test] as per-protocol analysis (134 participants); significant (P = 0.002) on an intention to treat analysis. 70% of the participants in AYUSH plus recovered during the first week (P = 0.046, Chi-square) and showed a significantly better change in physical health, fatigue, and quality of life measures. 48 adverse events, mostly mild and gut related, were reported by each group. There were 20 patient withdrawals (8 in AYUSH plus) but none due to an AE. There were no deaths. Daily assessment (hospitalization) and supervised drug intake ensured robust efficacy data. The open-label design was a concern (study outcome). CONCLUSIONS: AYUSH 64 in combination with SOC hastened recovery, reduced hospitalization, and improved health in COVID-19. It was considered safe and well-tolerated. Further clinical validation (Phase III) is required. TRIAL REGISTRATION: CTRI/2020/06/025557.

The Long-Term Effects of Short-Period Adalimumab Biosimilar Usage in Ankylosing Spondylitis.

Background Cost and drug toxicity frequently deter the long-term use of anti-tumor necrosis factor (TNF) agents in ankylosing spondylitis (AS). Therefore, this study was conducted to observe long-term relief after the short-term administration of an anti-TNF agent. Methodology A one-year, prospective, interventional, uncontrolled, single-center trial was conducted. There were 50 patients with symptomatic active chronic AS who received rheumatology therapy and were anti-TNF naive. Every two weeks, 40 mg of standard biosimilar adalimumab (Bs-ADA, Exemptia™) was administered subcutaneously for six injections (10 weeks) or to continue with standard follow-up if they did not achieve an Assessment in Ankylosing Spondylitis Response Criteria (ASAS 20) index response by week 12. Standard indicators (Assessment Spondyloarthritis International Society/ASAS and Bath) were used to evaluate progress. In addition, TNF-alpha, interleukin (IL)-6, and IL-17 were tested using a commercially available enzyme-linked immunosorbent assay kit from Bio Legend (Bengaluru, India). Results Patients experienced early and significant improvement in pain, non-steroidal anti-inflammatory drugs (NSAIDs) requirement, function, and several indices (ASAS 20 and 40, ASAS partial remission, Bath Ankylosing Spondylitis Disease Activity Index, Bath Ankylosing Spondylitis Functional Index, Ankylosing Spondylitis Disease Activity Score) after discontinuing injections. At weeks 12 and 48, 84% and 52% of patients showed ASAS 20 improvement, with 34% and 24% showing ASAS partial remission. Over half of the patients continued to improve and provided proof of concept. Conclusions In difficult-to-treat AS, a 10-week course of biosimilar adalimumab demonstrated significant early improvement that often lasted for 24 weeks. This unconventional method proved to be economically appealing. It merits further confirmation and acceptance, especially in resource-constrained contexts.

Corrigendum: Randomized, Double Blind, Placebo Controlled, Clinical Trial to Study Ashwagandha Administration in Participants Vaccinated Against COVID-19 on Safety, Immunogenicity, and Protection With COVID-19 Vaccine-A Study Protocol.

[This corrects the article DOI: 10.3389/fmed.2022.761655.].

Randomized, Double Blind, Placebo Controlled, Clinical Trial to Study Ashwagandha Administration in Participants Vaccinated Against COVID-19 on Safety, Immunogenicity, and Protection With COVID-19 Vaccine-A Study Protocol.

INTRODUCTION: Vaccines have emerged as the most effective tool in the fight against COVID-19. Governments all over the world have rolled out the COVID-19 vaccine program for their populations. Oxford-AstraZeneca COVID-19 vaccine (COVISHIELD™) is widely used in India. A large number of Indian people have been consuming various traditional medicines in the hope of better protection against COVID-19 infection. Several studies have reported immunological benefits of Withania somnifera (Ashwagandha) and its potential as a vaccine adjuvant. We propose to study the safety, immunogenicity and clinical protection offered by a 6-month regimen of Ashwagandha in participants who volunteer to be vaccinated against COVID-19 (COVISHIELDTM) in the ongoing national program of vaccination. METHODS AND ANALYSIS: We designed a prospective, randomized, double-blind, parallel-group, placebo-controlled, two-arm, exploratory study on healthy volunteers receiving the COVISHIELDTM vaccine. The administration of Ashwagandha will begin within 7 days of the first or second dose of COVISHIELDTM. Primary outcome measure is immunogenicity as measured by SARS-CoV-2 spike (S1) and RBD-specific IgG antibody titres. Secondary outcome measures are safety, protective immune response and quality of life measures. All adverse events will be monitored at each time throughout the study. Participants will be tracked on a daily basis with a user-friendly mobile phone application. Following power calculation 600 participants will be recruited per arm to demonstrate superiority by a margin of 7% with 80% power. Study duration is 28 weeks with interim analysis at the end of 12 weeks. ETHICS AND DISSEMINATION: Ethics approval was obtained through the Central and Institutional Ethics Committees. Participant recruitment commenced in December 2021. Results will be presented in conferences and published in preprints followed by peer-reviewed medical journals. CLINICAL TRIAL REGISTRATION: [www.ClinicalTrials.gov], identifier [CTRI/2021/06/034496].

Long term effectiveness of RA-1 as a monotherapy and in combination with disease modifying anti-rheumatic drugs in the treatment of rheumatoid arthritis.

BACKGROUND: Data on long term use of Ayurvedic drugs is sparse. They may prove useful if combined with modern medicine in certain clinical situations (integrative medicine). We present the results of a long term observational study of RA-1 (Ayurvedic drug) used in the treatment of rheumatoid arthritis (RA). OBJECTIVE: The objective was to study safety of long term use of RA-1 for treatment of rheumatoid arthritis (RA). MATERIALS AND METHODS: On completion of a 16 week randomized controlled study, 165 consenting volunteer patients were enrolled into a three year open label phase (OLP) study. Patients were symptomatic with persistent active disease and naïve for disease modifying anti-rheumatic drugs (DMARD). 57 patients were on fixed low dose prednisone. Patients were examined every 10-14 weeks in a routine rheumatology practice using standard care norms. They continued RA-1 (Artrex ™, 2 tablets twice daily) throughout the study period and were generally advised to lead a healthy life style. Based on clinical judgment, rheumatologist added DMARD and/or steroids (modified if already in use) to patients with inadequate response; chloroquine and/or methotrexate commonly used. Treatment response was assessed using American College of Rheumatology (ACR) efficacy measures and ACR 20% improvement index standard update statistical software (SAS and SPSS) were used; significant at p < 0.05. RESULTS: 158, 130 and 122 patients respectively completed evaluations at 1, 2 and 3 year primary end point. The ACR 20 response (range 34-40%) remained stable over three years (p = 0.33). Patients improved optimum for several measures by one year (p < 0.05) and this was sustained. The use of steroids varied from 42 to 49% patients at yearly end points (mean daily dose 5 mg prednisone); correspondingly the use of DMARD varied from 20 to 34% patients. 40% patients on RA-1 did not require DMARD/steroids for control of disease. 77% patients reported adverse events, albeit mild and mostly gut related, and not causing withdrawal. Several study limitations (especially self-selection) were reduced by the high patient retention and consistency in drug use. CONCLUSION: RA-1 is safe and effective in the long term management of symptomatic active chronic RA. DMARDs and/or steroids can be used judiciously along with RA-1 to treat difficult disease/flares. Further studies are required to evaluate RA-1 in early RA. This paves way for research and application of integrative therapeutic approach in clinical medicine.

Evaluation of the joint distribution at disease presentation of patients with rheumatoid arthritis: a large study across continents.

BACKGROUND: Genetic and environmental risk factors for rheumatoid arthritis (RA) are population dependent and may affect disease expression. Therefore, we studied tender and swollen joint involvement in patients newly diagnosed with RA in four countries and performed a subanalysis within countries to assess whether the influence of autoantibody positivity affected disease expression. METHODS: Patients with symptom duration <2 years fulfilling the American College of Rheumatology/European League Against Rheumatism 2010 RA classification criteria were selected from METEOR (Measurement of Efficacy of Treatment in the Era of Outcome in Rheumatology), an international observational database, and the Dutch Leiden Early Arthritis Clinic. Indian (n=947), Mexican (n=141), South African (n=164) and Dutch (n=947) autoantibody-positive and negative patients with RA, matched by symptom duration, were studied for swollen and tender joint distribution. RESULTS: Between countries, the reported distribution of swollen joint distribution differed, with more knee synovitis in Mexico, South Africa and India compared with the Netherlands (37%, 36%, 30% and 13%) and more elbow (29%, 23%, 7%, 7%) and shoulder synovitis (21%, 11%, 0%, 1%) in Mexico and South Africa compared with India and the Netherlands.Since the number of autoantibody-negative patients in Mexico and South Africa was limited, Indian and Dutch autoantibody-positive and negative patients with RA were compared. The number of swollen and tender joints was higher in autoantibody-negative patients, but the overall distribution of involved joints was similar. CONCLUSION: Joint involvement at diagnosis does not differ between autoantibody-positive and negative patients with RA in India and the Netherlands. However, joint involvement is reported differently across countries. More research is needed whether these differences are cultural and/or pathogenetic.

Effectiveness of chloroquine and inflammatory cytokine response in patients with early persistent musculoskeletal pain and arthritis following chikungunya virus infection.

OBJECTIVE: To evaluate whether chloroquine (CQ) is more effective than meloxicam for treating early musculoskeletal pain and arthritis following acute chikungunya (CHIK) virus infection. METHODS: During the 2006 CHIK epidemic, 509 rural community cases of acute CHIK virus infection were identified in the district of Sholapur in India. Seventy consenting adult patients (seropositive for IgM/IgG anti-CHIK antibody) with early persistent musculoskeletal pain and arthritis were randomized into a 24-week, 2-arm, parallel efficacy trial of CQ (250 mg/day) and meloxicam (7.5 mg/day). Assessors completed a rheumatology evaluation in a blinded manner and collected blood samples in the patients' homes, as per protocol. Laboratory parameters included serum cytokine assay (interleukin-6 [IL-6], interferon-γ [IFNγ], tumor necrosis factor α, CXCL10/IFNγ-inducible protein 10, and IL-13). Twenty-two patients who failed to meet the eligibility criteria (low pain cohort) were also followed up with similar evaluations. An intent-to-treat analysis was completed. At baseline, the 2 groups (38 patients randomized to receive CQ and 32 patients randomized to receive meloxicam) were well matched. RESULTS: There were no significant efficacy differences between the meloxicam group and the CQ group (mean changes in the visual analog scale score for pain -3.9 and -4.2, respectively). Patients improved significantly. Cytokine levels remained several-fold increased, were disproportionate to the clinical response, and were not different from those in the low pain cohort. Seven patients withdrew. Adverse events were mild and infrequent. CONCLUSION: This exploratory community intervention trial failed to identify an advantage of CQ over meloxicam to treat early musculoskeletal pain and arthritis following acute CHIK virus infection, but therapeutic efficacy of CQ was not ruled out. The inflammatory cytokine response was intense and was not consistent with clinical status.

An open label, prospective, clinical study on a polyherbal formulation in osteoarthritis of knee.

BACKGROUND: Currently, though pharmacological, mechanical, and surgical interventions are used, there is no known cure for osteoarthritis (OA). OBJECTIVES: The main aim of the study was to assess the efficacy and safety of "TLPL/AY/03/2008", a polyherbal formulation on knee joint pain assessed on visual analogue scale (VAS) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). MATERIALS AND METHODS: It was an open label, single center, prospective, clinical study conducted in 36 patients of OA Knee. Two capsules of 'TLPL/AY/03/2008' were given to all patients twice daily orally after meals for 180 days. RESULTS: Data describing quantitative measures are expressed as mean ± SD. Comparison of variables representing categorical data was performed using Chi-square test. The mean joint pain (as assessed on VAS) reduced significantly (59.85%; P < 0.05) and the mean WOMAC combined score, WOMAC pain sub-score, WOMAC stiffness sub-score, and WOMAC difficulty sub-score also reduced significantly at the end of the study. The mean time taken by the patients to walk 50 feet too, was reduced significantly (25.26%) at the end of the study. At the end of 4 months of the treatment, no patient needed paracetamol as rescue medicine to control pain. Most of the patients had shown good overall improvement assessed by the physician and by the patients. Majority of the patients showed excellent tolerability to the study drug. No significant change in most of the safety laboratory parameters was observed at the end of the study. CONCLUSION: The study provides good evidence in support of the efficacy and safety of the 'TLPL/AY/03/2008' in OA of knee.

Ayurvedic medicine offers a good alternative to glucosamine and celecoxib in the treatment of symptomatic knee osteoarthritis: a randomized, double-blind, controlled equivalence drug trial.

OBJECTIVE: To demonstrate clinical equivalence between two standardized Ayurveda (India) formulations (SGCG and SGC), glucosamine and celecoxib (NSAID). METHODS: Ayurvedic formulations (extracts of Tinospora cordifolia, Zingiber officinale, Emblica officinalis, Boswellia serrata), glucosamine sulphate (2 g daily) and celecoxib (200 mg daily) were evaluated in a randomized, double-blind, parallel-efficacy, four-arm, multicentre equivalence drug trial of 24 weeks duration. A total of 440 eligible patients suffering from symptomatic knee OA were enrolled and monitored as per protocol. Primary efficacy variables were active body weight-bearing pain (visual analogue scale) and modified WOMAC pain and functional difficulty Likert score (for knee and hip); the corresponding a priori equivalence ranges were ±1.5 cm, ±2.5 and ±8.5. RESULTS: Differences between the intervention arms for mean changes in primary efficacy variables were within the equivalence range by intent-to-treat and per protocol analysis. Twenty-six patients showed asymptomatic increased serum glutamic pyruvic transaminase (SGPT) with otherwise normal liver function; seven patients (Ayurvedic intervention) were withdrawn and SGPT normalized after stopping the drug. Other adverse events were mild and did not differ by intervention. Overall, 28% of patients withdrew from the study. CONCLUSION: In this 6-month controlled study of knee OA, Ayurvedic formulations (especially SGCG) significantly reduced knee pain and improved knee function and were equivalent to glucosamine and celecoxib. The unexpected SGPT rise requires further safety assessment. TRIAL REGISTRATION: Clinical Drug Trial Registry-India, www.ctri.nic.in, CTRI/2008/091/000063.

Evaluating higher doses of Shunthi - Guduchi formulations for safety in treatment of osteoarthritis knees: A Government of India NMITLI arthritis project.

BACKGROUND: Results of an exploratory trial suggested activity trends of Zingiber officinale-Tinopsora cordifolia (platform combination)-based formulations in the treatment of Osteoarthritis (OA) Knees. These formulations were "platform combination+Withania somnifera+Tribulus terrestris" (formulation B) and "platform combination+Emblica officinale" (formulation C). This paper reports safety of these formulations when used in higher doses (1.5-2 times) along with Sallaki Guggul and Bhallataka Parpati (a Semecarpus anacardium preparation). MATERIALS AND METHODS: Ninety-two patients with symptomatic OA knees were enrolled in a 6 weeks investigator blind, randomized parallel efficacy 4-arm multicenter drug trial. The 4 arms were (I) formulation B, 2 t.i.d.; (II) formulation B, 2 q.i.d.; (III) platform combination+Sallaki Guggul; (IV) Bhallataka Parpati+formulation C. A detailed enquiry was carried out for adverse events (AE) and drug toxicity as per a priori check list and volunteered information. Laboratory evaluation included detailed hematology and metabolic parameters. Patients were examined at baseline, first and fourth weeks, and on completion. Standard statistical program (SPSS version 12.5) was used for analysis. RESULTS: None of the patients reported serious AE or withdrew due to any drug-related toxicity. Mild gut-related (mostly epigastric burning) AE was reported. A mild increase in liver enzymes [serum glutamic pyruvate transaminase (SGPT), serum glutamic oxaloacetic transaminase (SGOT)] without any other hepatic abnormality was reported in 2 patients (group IV). Other laboratory parameters remained normal. The mean improvement in active pain visual analog scale (1.4, CI 0.5-2.22), WOMAC (functional activity questionnaire) pain score (1.37, CI 0.22-2.5), and urinary C-TAX (cartilage collagen breakdown product) assay was maximum (NS) in group IV. Lower dose group I showed numerically superior improvement compared with higher dose group II. CONCLUSION: The results suggested that despite higher doses, standardized Ayurvedic formulations demonstrated a good safety profile. An improved efficacy and likely chondroprotective effect was shown by group IV intervention. A confirmatory drug trial with adequate power and sample size was planned based on the learning from this trial.

Comparable efficacy of standardized Ayurveda formulation and hydroxychloroquine sulfate (HCQS) in the treatment of rheumatoid arthritis (RA): a randomized investigator-blind controlled study.

Hydroxychloroquine sulfate (HCQS) is a popular disease-modifying antirheumatic drug (DMARD) despite modest efficacy and toxicity. Ayurveda (ancient India medicinal system) physicians treat rheumatoid arthritis (RA) with allegedly safer herbal formulations. We report a head-to-head comparison in an exploratory drug trial. The objective is to compare standardized Ayurvedic formulations and HCQS in the treatment of RA. One hundred twenty-one patients with active moderately severe RA (ACR 1988 classified) were randomized into a 24-week investigator-blind, parallel efficacy, three-arm (two Ayurvedic and HCQS) multicenter drug trial study; polyherb (Tinospora cordifolia and Zingiber officinale based) and monoherb (Semecarpus anacardium). Study measures included joint counts (pain/tenderness and swelling), pain visual analogue scale, global disease assessments, and health assessment questionnaire. Oral meloxicam (fixed-dosage schedule) was prescribed to all patients during the initial 16 weeks. Patients on prednisolone could continue a fixed stable dose (<7.5 mg daily). Rescue oral use of paracetamol was permitted and monitored. All groups matched well at baseline. An intent-to-treat analysis (ANOVA, significance P < 0.05) did not show significant differences by treatment groups. In the polyherb, monoherb, and HCQS arms, 44%, 36%, and 51%, respectively, showed ACR 20 index improvement. Several efficacy measures improved significantly in the HCQS and polyherb groups with no difference between the groups (corrected P). However, the latter was individually superior to monoherb. Only mild adverse events (gut and skin, and none withdrew) were reported with no differences between the groups. Forty-two patients dropped out. This preliminary drug trial controlled for HCQS demonstrated a standardized Ayurvedic polyherb drug to be effective and safe in controlling active RA. A better-designed study with a longer evaluation period is recommended.

A Randomized Controlled Exploratory Evaluation of Standardized Ayurvedic Formulations in Symptomatic Osteoarthritis Knees: A Government of India NMITLI Project.

The multidisciplinary "New Millennium Indian Technology Leadership Initiative" Arthritis Project was undertaken to validate Ayurvedic medicines. Herbal formulations in popular use were selected by expert consensus and standardized using modern tools. Our clinical strategy evolved from simple exploratory evaluations to better powered statistically designed drug trials. The results of the first drug trial are presented here. Five oral formulations (coded A, B, C, D and E), with a common base of Zingiber officinale and Tinospora cordifolia with a maximum of four plant extracts, were evaluated; with placebo and glucosamine as controls. 245 patients suffering from symptomatic OA knees were randomized into seven arms (35 patients per arm) of a double blind, parallel efficacy, multicentric trial of sixteen weeks duration. The groups matched well at baseline. There were no differences for patient withdrawals (17.5%) or adverse events (AE) of mild nature. Intention-to-treat efficacy analysis, demonstrated no significant differences (P < .05) for pain (weight bearing) and WOMAC questionnaire (knee function); placebo response was high. Based on better pain relief, significant (P < .05) least analgesic consumption and improved knee status, "C" formulation was selected for further development. Controlled exploratory drug trials with multiple treatment arms may be used to economically evaluate several candidate standardized formulations.

Ayurveda-modern medicine interface: A critical appraisal of studies of Ayurvedic medicines to treat osteoarthritis and rheumatoid arthritis.

The potential of Ayurvedic philosophy and medicines needs to be recognized and converted into real life treatment paradigm. This article describes a comprehensive therapeutic approach used in Ayurveda and modern medicine to treat arthritis. We present concise summary of various controlled drug trials carried out by us to validate standardized Ayurvedic drugs using modern medicine protocol to treat Rheumatoid Arthritis and Osteoarthritis knees. Several of the latter are published. The trials consistently demonstrate excellent safety of Ayurvedic medicines but often fail to unequivocally show superior efficacy. Some key findings of a recently unpublished trial in OA knees are also presented to show equivalence between Ayurvedic medicine and celecoxib and glucosamine, and we speculate that equivalence trials may be a way forward. The data from the trials also supports the Ayurvedic 'Rasayana' concept of immune-modulation and healing. We need to interpret logic of Ayurveda when, adopting modern science tools in drug development and validation and much research is required. Validation of Ayurvedic medicines using the latter approach may lead to an evidence based Ayurveda - Modern Medicine interface. Also, in pursuit of finding better treatment solutions, we ought to step beyond the realm of only drugs and attempt validation of comprehensive specific treatment package as per classical Ayurveda. Finally, validation of a combined (Ayurveda and modern medicine) therapeutic approach with superior efficacy and safety is likely to be a major leap in overcoming some of the current frustrations to treat difficult disorders like arthritis using only modern medicines.

Leflunomide (Arava) is a useful DMARD in Indian (Asian) patients: a clinic-based observational study of 1-year treatment.

Several drug trials, predominantly of Caucasian patients, have demonstrated the therapeutic role of leflunomide (LEF) in the treatment of rheumatoid arthritis (RA). We report an Indian (Asian) experience from a prospective observational study. Two hundred thirty affording patients with moderately severe active RA (naïve for LEF), mostly failing methotrexate (MTX), were begun LEF (Aravatrade mark; 20 mg daily, post loading 100 mg od x 3 days) in a clinic setting and followed regularly in an open cohort as per standard of care practice guidelines. A priori, LEF was to be preferably used as a single-agent disease-modifying anti-rheumatic drug (DMARD). One hundred forty-three patients and 87 patients were clinically assigned to the LEF monotherapy and LEF + MTX combination, respectively; less than one third received prednisolone. We focus on 146 patients (64%) completing 1 year treatment. Patients improved significantly (p < 0.05, analysis of variance) in several measures (including Health Assessment Questionnaire). Though unintended (non-randomized), the treatment subgroups matched at baseline. Of patients, 42% and 24% in LEF monotherapy and LEF + MTX, respectively showed American College of Rheumatology 50% Response Criteria (ACR 50) improvement. LEF monotherapy showed a better 'time to first ACR 20 improvement' outcome over 1 year (survival function curve, Cox Hazard Ratio = 0.71, 95% confidence interval 0.52, 0.96). Ten percent to 30% patients reported diarrhea, hair loss, skin rash, and dyspepsia; <3% reported abnormal liver functions. Eighty-four patients (36.5%) withdrew (8.7% adverse events and 18.7% non-affordability). LEF is an effective and safe DMARD in our ethnic patient population and may suffice as a single agent (to treat moderately severe RA) during the initial 1 year.

Pain and disability, perceptions and beliefs of a rural Indian population: A WHO-ILAR COPCORD study. WHO-International League of Associations for Rheumatology. Community Oriented Program for Control of Rheumatic Diseases.

OBJECTIVE: The WHO-ILAR Community Oriented Program for Control of Rheumatic Diseases (COPCORD) primarily aims to estimate the burden of rheumatic-musculoskeletal symptoms/disorders (RMS). We investigated data on pain and disability, perceptions and beliefs in the first rural community based COPCORD study in India. METHODS: A total of 4092 adults were interviewed (response rate 89%) in a population survey (Stage 1) in Bhigwan village in 1996 using modified COPCORD core questionnaires. Twenty-one trained volunteers completed the survey in 5 weeks. Those reporting RMS were identified (Phase 1) to complete a self-evaluation questionnaire (Phase 2) prior to rheumatological evaluation (Phase 3). Phase 2 included questions on perceptions and beliefs regarding pain, effect on life, work and socioeconomic factors, disability, and therapy; only the moderate and severe grades were considered significant. Patients marked their pain sites on a manikin during the presurvey week. A validated modified Health Assessment Questionnaire disability index (HAQDI) in the local language evaluated functional disability. RESULTS: RMS were the predominant ailments reported by 746 adult villagers (18.2%; 95% CI 17.1, 19.2). Moderate pain of > 2 years' duration was reported by almost 60% of RMS patients. Neck (6%), lumbar (11.4%), shoulder (7.4%), elbow (6.5%), wrist (6.4%), hand (6.1%), knee (13.2%), calf (6.6%), and ankle (6.5%) were the common painful sites, predominantly in women; 91%, 89%, and 31% with RMS reported a significant grade of pain, RMS illness, and disturbed sleep, respectively. In the age group 25-54 years, 21% of those with RMS perceived a significant effect on work ability, while less than 20% of those with RMS admitted a similar effect on their personal life (including finances). About 10% with RMS had ceased to work because of RMS. Among RMS subjects 21% scored a significant HAQDI, but many more reported significant difficulty (HAQ) in the individual items of walking, hygiene (squatting), arising (from sitting cross-legged), reaching, and occupational/household chores; this corresponded to the dominant pain sites in low back and lower limbs. Oral tobacco use was reported to be significantly greater (p < 0.001) in the RMS patients. Past trauma was recalled by 23% of patients, and many connected this to their RMS. Modern medicines were consumed by 55% of patients with RMS. Among patients, 86% and 65% expected "pain relief" and "cure," respectively, from their doctor; 23% of patients wanted greater sympathy and attention. However, 21% of patients had never visited a doctor and were only identified by the COPCORD study. CONCLUSION: The findings of this study (1) demonstrate that RMS, although a predominant ailment, has a modest effect on daily living in most subjects with RMS; (2) indicate there is inconsistency between the measures of pain and disability (using HAQ) and their effects; (3) describe the beliefs and expectations of the community. Based on the data and community support, the COPCORD has been continued for Stages II and III, especially with a view to health education.