CRD - Research - Drug Trials

IRA-01, An Ayurvedic (Asian Indian) drug for Rheumatoid Arthritis (RA): Evaluation for Efficacy and Safety, and a Probable lipid modifying effect

A. CHOPRA, M. SALUJA, J. Patil, ANURADHA. VENUGOPALAN, L. BICHILE
RHEUMATOLOGY, CENTRE FOR RHEUMATIC DISEASES, RHEUMATOLOGY, KEM HOSPITAL AND MEDICAL COLLEGE MUMBAI, PUNE, INDIA.

Background

The ancient Ayurveda continues to be popularly practised in India to treat arthritis. IRA-01, a polyherbal drug, was prepared as per Ayurvedic norms and standardized prior to its evaluation in RA.

Objectives

to evaluate the efficacy and safety, and a hypothesized lipid modifying effect of IRA-01 in patients with RA

Methods

130 patients (111 females) of RA (ACR classified) with active disease were randomized (active= 65, placebo=65) in a three month double blind (RDB) multicentric drug trial. In single CRD centre (84 patients entered), those willing were followed up(FU) for 1 year (OLP). The study design (80% power to detect 20% difference between groups; significance p<0.05) was based on a hypothesis of slow onset DMARD effect and an earlier report . No NSAID, DMARD, or Steroids were permitted. Paracetamol use as & when basis was monitored. IRA-01 was administered 2 capsules (800 mg) thrice daily without dietary or any other restrictions. The primary efficacy measures were ACR core set & ACR 20 response. A validated Indian version of modified HAQ was scored. This is an intent-to-treat analysis. The active and the placebo groups were well matched (NS) at baseline (0 mths)[JC: joint count (ACR 68 joint); PT: pain/tender; SW: swelling; phy: physician; pat: patient; Global: global disease activity (0-10 cms scale); painVAS: 0-10 cms scale; HAQ: Health Assessment Questionnaire(max score=24); mths: month; NS: not statistically significant; act: active; plb: placebo; RF: rheumatoid factor titre (IU/ml); OLP: open label phase]

Results

         The median age and median disease duration was 41 years (20-74 yrs) and 3years (1-32 yrs) resp. RF & erosions were recorded in 59% and 40% resp.

        Efficacy (a) In the RDB, though the IRA-01 patients improved significantly, they did not differ significantly from the placebo (ACR 20: active= 60%, placebo=53%). (b)OLP: The Table shows significant improvement (p<0.05) in the mean values of clinical measures in the 58 patients who completed 12 mths. (c)The mean RF at 6 mths showed impressive reduction in the act group (0 mths= 364; 6 mths=212) while it worsened in the plb(0 mths =258, 6 mths=426).

        Lipid Profile (mg/dl): At 3 mths, IRA-01 showed a significant change(p<0.05) in HDL (baseline= 45.6 , increase=1.6 ) and LDL(baseline=117.1; reduction=12.7)on comparison to placebo ; a similar effect was seen at 1 year FU( HDL= 47.1,LDL= 106.8).

        Adverse Events (AE)/Withdrawals: Only mild clinical AE /toxicity (mostly related to GIT -gastritis, anorexia, nausea) reported; no difference between active and placebo. 38 patients (29%) withdrew during RDB (failure in follow up or test drug compliance).

Table

Variable	Baseline (mean)	12 mths (mean)	Mean change (95% CI)
JCPT	24.3	5.5	15.7, 21.8
JCSW	9.5	1.6	6.1 ,9.6
painVAS	6.6	3.6	2.4, 3.5
patGlobal	6.4	3.4	2.5, 3.5
phyGlobal	5.7	2.6	2.6, 3.6
HAQ	8.8	4.4	3.3, 5.4
ESR (W?gren)	61.4	66	-12.9, 3.5
ACR 20		80%
ACR 50		40%

Conclusion

Against an unexpected strong placebo response, the IRA-01 demonstrated a fair DMARD effect on one year FU. The safety profile was excellent. The observed favourable lipid profile needs to be explored further while enhancing the anti-inflammatory effect of IRA-01 SPONSORSHIP & FUNDING: This study was funded and sponsored by Indus Biotech Pvt Ltd, Pune.

References

1) J Rheumatol 2000:27; 1365-72

2) Arth Rheum 1993: 36; 729-40

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