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

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Abstract

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.

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References

  1. Barnes PM, Bloom B, Nahin RL (2008) Complementary and alternative medicine use among adults and children: United States, 2007. National Health Statistics Reports, no. 12. National Center for Health Statistics, Hyattsville

  2. Sharma PV (1994) Caraka Samhita (English translation). Chikitsa Sthana, Chapter 28. Chaukhambia Orientalia, Delhi

  3. Srikanta Murthy KR (1993) Madhava Nidanam (roga viniscaya) of Madhavakara (English translation), chapter 22. Chaukhambia Orientalia, Delhi

  4. Chopra A (2002) Ayurvedic medicine. Core concept, therapeutic principles, and current relevance. Med Clin N Am 86:75–89

    Article  PubMed  Google Scholar 

  5. Kulkarni RR, Patki PS, Jog VP, Gandage SG, Patwardhan B (1991) Treatment of osteoarthritis with a herbomineral formulation: a double-blind, placebo-controlled, cross-over study. J Ethnopharmacol 33(1–2):91–95

    Article  PubMed  CAS  Google Scholar 

  6. Chopra A, Lavin P, Patwardhan B, Chitre D (2000) Randomized double blind trial of an Ayurvedic plant derived formulation for treatment of rheumatoid arthritis. J Rheumatol 27:1365–1372

    PubMed  CAS  Google Scholar 

  7. Chopra A, Lavin P, Patwardhan B, Chitre D (2004) A 32-week randomized, placebo-controlled clinical evaluation of RA-11, an Ayurvedic drug on osteoarthritis of the knees. J Clinical Rheumatol 10:236–245

    Article  Google Scholar 

  8. Chopra A, Saluja M, Patil J, Anuradha V, Bichile L (2004) IRA-01, an Ayurvedic (Asian Indian) drug for rheumatoid arthritis (RA): evaluation for efficacy and safety, and a probable lipid modifying effect. Ann Rheum Dis 63:275

    Google Scholar 

  9. Chopra A, Saluja M, Tillu G, Venugopalan A, Sarmukkadam S, Raut AK et al (2011) A randomized controlled exploratory evaluation of standardized Ayurvedic formulations in symptomatic osteoarthritis knees: a government of India NMITLI project. Evid Based Complement Alternat Med 2011:724291. doi:10.1155/2011/724291

    Article  PubMed  Google Scholar 

  10. Patwardhan B, Vaidya ADB, Chorghade M, 6 (2004) Ayurveda and natural products drug discovery. Current Science 86:789–799

    Google Scholar 

  11. Mashalkar R (2008) Second World Ayurveda Congress (theme: Ayurveda for the future)—inaugural address: part I. Lecture Series eCAM 5(2):129–131

    Google Scholar 

  12. Mashalkar R (2008) Second World Ayurveda Congress (theme: Ayurveda for the future)—inaugural address: part II. Lecture Series eCAM 5(3):243–245

    Google Scholar 

  13. Saag KG, Teng GG, Patkar NM, Anuntiyo J, Finney C, Curtis JR et al (2008) American College of Rheumatology 2008 recommendations for the use of nonbiologic and biologic disease-modifying antirheumatic drugs in rheumatoid arthritis. Arthritis & Rheumatism (Arthritis Care & Research) 59:762–784

    Article  CAS  Google Scholar 

  14. Gogate VM (2000) Ayurvedic text on clinical pharmacology In: Ayurvedic pharmacology and therapeutic uses of medicinal plants—Dravyaguna Vidnyan, 1st English edn. Bharatiya Vidya Bhavan, Mumbai, 310

  15. (2001) The Ayurvedic pharmacopoeia of India, vol. I: part I. Reprint. The Controller of Publications, Delhi. ISBN: 81-901151-3-8.

  16. OECD Guidelines Number 423. Available at http://www.oecd.org/dataoecd/17/50/1948370.pdf

  17. Arnett FC, Edworthy SM, Bloch DA, McShane DJ, Fries JF, Cooper NS et al (1988) The American Rheumatism Association 1987revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum 31:315–324

    Article  PubMed  CAS  Google Scholar 

  18. Bellamy N (1993) Musculoskeletal clinical metrology. Kluwer Academic, Boston

    Book  Google Scholar 

  19. Felson DT, Anderson JJ, Boers M, Bombardier C, Chernoff M, Fried B et al (1993) The American College of Rheumatology preliminary core set of disease activity measures for rheumatoid arthritis clinical trials. Arthritis Rheum 36:729–740

    Article  PubMed  CAS  Google Scholar 

  20. Chopra A (2004) Rheumatology: made in India (Camps, COPCORD, HLA, Ayurveda, HAQ, WOMAC and drug trials). J Indian Rheum Assoc 12:43–53

    Google Scholar 

  21. Felson DT, Anderson JJ, Boers M et al (1995) American College of Rheumatology preliminary definition of improvement in rheumatoid arthritis. Arthritis Rheum 38:727–735

    Article  PubMed  CAS  Google Scholar 

  22. Chopra A, Saluja M, Tillu G (2010) Ayurveda–modern medicine interface: a critical appraisal of studies of Ayurvedic medicines to treat osteoarthritis and rheumatoid arthritis. J Ayurveda Integr Med 1(3):190–198

    Article  PubMed  Google Scholar 

  23. Chopra A, Narasimulu G, Bichile L et al (2007) Comparing Ayurvedic (Indian) herbal drugs and HCQS (hydroxychloroquine sulphate) in the treatment of rheumatoid arthritis (RA): A randomized, double blind, multi-centric exploratory drug trial of 24 weeks duration. Arthritis & Rheumatism 56(9):394–395, Abstract

    Google Scholar 

  24. Thatte U, Chhabria S, Karandikar SM, Dahanukar S (1987) Immuno-therapeutic modifications by Indian medicinal plants. Indian Drugs 25:85–87

    Google Scholar 

  25. Thatte UM, Dahanukar SA (1989) Immunotherapeutic modification of diverse infectious states by Indian medicinal plants. Phytother Res 3:43–48

    Article  Google Scholar 

  26. Rege NN, Thatte UM, Dahanukar SA (1999) Adaptogenic properties of six rasayana herbs used in Ayurvedic medicine. Phytother Res 13:275–291

    Article  PubMed  CAS  Google Scholar 

  27. Budhiraja RD, Sudhir S (1987) Review of biological activity of withanolides. J Sci Ind Res 46:400–408

    Google Scholar 

  28. Ghosal S, Lal J, Shrivastava R, Bhattacharya SK, Upadhyay SN, Jaiswal AK et al (1989) Immunomodulatory and CNS effects of sitoinosides IX and X, two new glycowithanolides from W. somnifera. Phytother Res 3:201

    Article  CAS  Google Scholar 

  29. Ziauddin M, Phansalkar N, Patki P, Diwanay S, Patwardhan B (1996) Studies on the immunomodulatory effects of Ashwagandha. J Ethnopharmacol 50:69–76

    Article  PubMed  CAS  Google Scholar 

  30. Chopra A, Patil J, Doiphode V, Patwardhan B (2001) Exploring ancient Ayurveda for rheumatology: traditional therapy, modern relevance and challenges. APLAR J Rheumatol 4:190–199

    Google Scholar 

  31. Sumantran V, Kulkarni A, Chandwaskar R, Harsulkar A, Patwardhan B, Chopra A, Wagh U (2007) Chondroprotective potential of fruit extracts of Phyllanthus emblica in osteoarthritis. Evid Based Complement Alternat Med 5:329–335

    Article  Google Scholar 

  32. Sumantran V, Kulkarni A, Boddul S, Chinchwade T, Koppikar S, Harsulkar A, Patwardhan B, Chopra A, Wagh U (2007) Chondoprotective potential of root extracts of Withania somnifera in osteoarthritis. J Biosci 32(2):299–307

    Article  PubMed  Google Scholar 

  33. Chopra A (2000) Ayurvedic medicine and arthritis. Rheum Dis Clin North Am 26:133–144

    Article  PubMed  CAS  Google Scholar 

  34. Myasoedova E, Davis JM, Crowson DS, Gabriel SE (2012) Epidemiology of rheumatoid arthritis and mortality. Curr Rheumatol Rep 12:379–385

    Article  Google Scholar 

  35. Felson DT, Anderson JJ, Meenan RF (1990) The comparative efficacy and toxicity of second line drugs in rheumatoid arthritis: results of two meta-analyses. Arthritis Rheum 33(10):1449–1461

    Article  PubMed  CAS  Google Scholar 

  36. Little CV, Parsons T (2001) Herbal therapy for treating rheumatoid arthritis. Cochrane Database of Syst Rev (1):CD002948. doi:10.1002/14651858.CD002948

  37. Soeken KL, Miller SA, Ernst E (2003) Herbal medicines for the treatment of rheumatoid arthritis: a systematic review. Rheumatology 42:652–659

    Article  PubMed  CAS  Google Scholar 

  38. Salahuddin A, Jeremy A, Charles JM, Haqqi TM (2005) Biological basis for the use of botanicals in osteoarthritis and rheumatoid arthritis: a review. Evid Based Complement Alternat Med 2(3):301–308. doi:10.1093/ecam/neh117

    Article  Google Scholar 

  39. Chopra A, Saluja M, Tillu G (2010) Ayurveda modern medicine interface: a critical appraisal of studies of Ayurvedic medicines to treat osteoarthritis and rheumatoid arthritis. J Ayurveda Integrative Med (J-AIM) V1(3):190–198

    Article  Google Scholar 

  40. Bansal D, Hota D, Chakrabarti A (2010) Research methodological issues in evaluating herbal interventions. Open Access Journal of Clinical Trials 2:15–21

    Google Scholar 

  41. Tonelli MR, Callahan TC (2001) Why alternative medicine cannot be evidence based? Acad Med 76(12):1213–1220

    Article  PubMed  CAS  Google Scholar 

  42. Fonnebo V, Grimsgaard S, Walach H, Ritenbaugh C, Norheim AJ, MacPherson H et al (2007) Researching complementary and alternative treatments—the gatekeepers are not at home. BMC Med Res Methodol 7:7. doi:10.1186/1471-2288-7-7

    Article  PubMed  Google Scholar 

  43. Narahari SR, Ryan TJ, Aggithaya MG, Bose KS, Prasanna KS (2008) Evidence based approaches for the Ayurvedic traditional herbal formulations: toward an Ayurvedic CONSORT model. The J of Alternative and Complementary Medicine 14(6):769–776

    Article  Google Scholar 

  44. MacPherson H (2004) Pragmatic clinical trials. Complementary Therapies in Medicine 12:136–140

    Article  PubMed  Google Scholar 

  45. Elder C, Aickin M, Bauer V et al (2006) Randomized trial of a whole-system Ayurvedic protocol for type 2 diabetes. Alternative Therapies 12(5):24–30

    Google Scholar 

  46. Sarmukaddam S, Chopra A, Tillu G (2010) Efficacy and safety of Ayurvedic medicines: recommending equivalence trial design and proposing safety index. International J Ayurveda Res (IJAR) V1(3):175–180

    Article  Google Scholar 

  47. Mashalkar R (2008) Second World Ayurveda Congress (theme: Ayurveda for the future)—inaugural address: part III. Lecture Series eCAM 5(4):367–369

    Google Scholar 

  48. Chopra A, Saluja M, Tillu G (2011) Diet, Ayurveda and interface with biomedicine (letter to the editor). J Ayurveda Integr Med 1:243–244. doi:10.4103/0975-9476.74423

    Article  Google Scholar 

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Acknowledgements

This study was funded by the NMITLI Cell, TNBD Division of the Council of Scientific and Industrial Research, Government of India and we thank Yogeshwar Rao, Meenakshi Singh, and Vibha Malhotra for the administrative support. We thank senior Ayurveda physician, Vaidya Y.G. Joshi for his generous contribution to provide information on the BPRT formulation used in this trial and further supervising its preparation. We also acknowledge contributions of the expert staff and NMITLI aesearch associates and fellows, namely, Dr. Jaishree Patil (Ayurvedic physician, CRD), Dr. Sridevi (Ayurvedic physician, NIMS), Dr. Nilambari (Ayurvedic physician, KEM), Dr. S. Garad (statistics), Mr. Ravi Ghorpade (laboratory and database, CRD), and Mr. Deepak S. (programmer, CRD). We also thank Kalpana Joshi (NMITLI research associate, SHS) and other NMITLI research fellows from SHS (Dnyaneshwar Warude, Manish Gautam, Preeti Chavan, and Yogita Ghodke). Several other colleagues and staff at the clinical drug trial centers also participated and provided administrative and logistic support and professional help. Several senior NMITLI experts provided invaluable assistance, in particular, Dr. G.N. Qazi, Dr. V. Sumantran, Dr. Ulhas Wagh, Dr. Ashok Vaidya, Dr. Rama Vaidya, Dr. A.M. Majumdar, and Dr. Pushpagandhan. The Ayurvedic formulation drugs were principally developed in SHS and further standardized in Natural Remedies, Bangalore. Animal toxicity and mechanism of action studies were carried out in ARI. The drug trial protocols were principally developed and coordinated by CRD.

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Authors and Affiliations

  1. Centre for Rheumatic Diseases (CRD), 1988 Convent Street, Hermes Elegance, Camp, Pune, 411001, India

    Arvind Chopra, Manjit Saluja, Anuradha Venugopalan & Sanjeev Sarmukaddam

  2. Interdisciplinary School of Health Sciences (SHS), University of Pune, Pune, 411007, India

    Girish Tillu & Bhushan Patwardhan

  3. Rheumatology Department, Nizam Institute of Medical Sciences (NIMS), Panjagutta, Hyderabad, 500082, India

    Gumdal Narsimulu

  4. Rheumatology Department, All India Institute of Medical Sciences (AIIMS), Ansari Nagar, New Delhi, 110029, India

    Rohini Handa

  5. Rheumatology Department, KEM Hospital and GS Medical College and SPARC, Parel, Mumbai, 400012, India

    Lata Bichile & Ashwinikumar Raut

Authors
  1. Arvind Chopra
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  2. Manjit Saluja
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  3. Girish Tillu
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  4. Anuradha Venugopalan
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  5. Gumdal Narsimulu
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  6. Rohini Handa
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  7. Lata Bichile
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  8. Ashwinikumar Raut
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  9. Sanjeev Sarmukaddam
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  10. Bhushan Patwardhan
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Corresponding author

Correspondence to Arvind Chopra.

Additional information

Trial registration: ICMR CTRI registry, TEMP UTRN 115644567-050320101825344

Key messages

(1) Since ancient times, the Indian (Asian) Ayurvedic medicinal system advocates a holistic approach including herbal formulations to treat RA.

(2) A standardized Ayurvedic drug is demonstrated to be a good alternative DMARD to hydroxychloroquine in treating RA.

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Chopra, A., Saluja, M., Tillu, G. et al. Comparable efficacy of standardized Ayurveda formulation and hydroxychloroquine sulfate (HCQS) in the treatment of rheumatoid arthritis (RA): a randomized investigator-blind controlled study. Clin Rheumatol 31, 259–269 (2012). https://doi.org/10.1007/s10067-011-1809-z

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