Comparative Analysis of Analgesic Efficacy, Safety and Compliance of fixed dose combination (Aceclofenac+ Diacerein) versus free drug combination in 4oo patients of early Osteoarthritis knee

Tabasum Jawed Bhat, Jawed Ahmad Bhat, Faizan Bhat

Abstract


Introduction: Osteoarthritis is a major cause of disability and is among the most frequent forms of musculoskeletal disorders. The goal of pharmacological treatment is usually to control symptoms of the disease, pain, and limitation of function, which is traditionally accomplished by the use of analgesic agents or non-steroidal antinflammatory drugs (NSAIDS).

Aims and Objectives: 1) To evaluate analgesic efficacy, safety and compliance of fixed drug combination (Aceclofenac + Diacerein) in patients of early OA Knee. 2) To compare analgesic efficacy, safety and compliance of compliance of free drug combination (Aceclofenac followed by Diacerein) with fixed drug combination (Aceclofenac + Diacerein) in patients of early OA knee. 

Study Design: The present study was a randomized, open label trial to compare the analgesic efficacy, safety and compliance of fixed drug combination (Aceclofenac + Diacerein) with free dose combination (Aceclofenac, Diacerein) in patients of early Osteoarthritis knee. 

Result: In present study, pain parameters showed improvement in both groups on Visual analog scale, Womac scale and Global assessment scale. The post drug values decreased in both groups at all levels (P value<0.0001) on all scales, however on inter group comparison both drug regimes were equally efficacious on all scales as there was no statistical difference amongst them (P value > 0.05). Review of the literature revealed no study where fixed dose combination or free drug combination of Aceclofenac and Diacerein were compared. However, there are number of studies comparing the drugs under investigation with other analgesics.

Conclusion: Current study demonstrated equal efficacy, safety and compliance of the both drug regimes of free drug combination (Aceclofenac, Diacerein) and fixed dose combination (Aceclofenac + Diacerein) in patients of early OA knee. None of the drug regimes showed superiority over other.


Keywords


fixed dose,OA,

References


. Louthrenoo W, Nilganuwong S, Aksaranugraha, et al. The efficacy, safety & carry over effect of Diacerein in the treatment of painful knee Osteoarthritis: a randomized, double-blind, NSAID-controlled study. Osteoarthritis Research Society International. 2007; 15: 605-614.

. Dezii CM. A retrospective study of persistence with single pill combination therapy vs. concurrent two pill therapy in patients with hypertension. Manag Care.200; 9(9): 2-6.

. Hilal G, Martel PJ, Pelletier JP, et al. Osteoblast like cells from human subchondral osteoarthritic bone demonstrates an altered phenotype in vitro: possible role in subchondral bone sclerosis. Arthritis Rheum .1998; 41(5):891-9.

. Mansell JP, Bailey AJ. Abnormal cancellous bone collagen metabolism in Osteoarthritis Clin Invest. 1998; 101(8):1596-1603.

. Lajeunesse D, Hilal G, Pelletier JP et al. Subchondral bone morphological and biochemical alterations in Osteoarthritis. Osteoarthritis Cartilage. 1999; 7(3): 321-2.

. Lawrence RC, Falcon DT, Helmick CG, et al. Estimates of the Prevalance of arthritis and other rheumatic conditions in the United States. Arthritis Rheum. 2008; 58: 26-35.

. McConnell S, Kolopack P, Davis AM. The Western Ontario and Mcmaster Universities Osteoarthritis Index (WOMAC): a review of its utility and measurement properties. Arithritis Rheum. 2001; 45(5): 453-461.

. Alhasmi AM. Knee Osteoarthritis related pain: a narrative review of diagnosis and treatment. International Journal of Health Sciences, Qassim University.2014; 8(1): 86-104.

. Aggaral V. Prevalance of Rheumatic diseases in India. JK Science. 2003; 5(2): 48-49.

. Mahajan A, Jasrotia DS, Manhas AS, Jammal SS. Prevalance of Rheumatic disorders in Jammu. JK science. 2003; 5 (2): 63-66.

. Dilip k, Shobana M, Jagdiswar R. Evaluation of Efficacy & Safety of Diacerein in Osteoarthritis of knee joint. International Journal of Pharma & Bio sciences. 2010; 1(3): 1-12.

. Polisson R. Innovative therapies in Osteoarthritis. Curr Rhematol Rep. 2001; 3(6): 489-95.

. Fransen M, Bridgett L, March l, et al. The epidemiology of Osteoarthritis in Asia. International Journal of Rheumatic Diseases.2011; 14(2): 113-121.

. Joern W, Micheal P, Klaus U, et al. The Epidemiology, Etiology, Diagnosis and Treatment of Osteoarthritis of the knee. Dtsch Arztebl Int. 2010; 107(9): 152-62.

. Mahajan A, Kulbir S, Vishal R, et al. Diacerein: A symptomatic slow acting drug for Osteoarthritis. JK science. 2006; 8(3): 173-75.

. Saraf S. Aceclofenac: A potent Non-Steroidal Anti-inflammatory Drug. Pharmaceutical information.net. 2006 May; 45.

. Mehdi B, Singh PK, Prakash A, Sen R, et al. Diacerein: A new Disease Modulating Agent in Osteoarthritis. IJPMI 2007; 18(2): 48-52.

. Petrillo M, Montrone F, Adrizzone S, et al. Endoscopic evaluation of di-acetylrehin induced gastric mucosal lesion. Curr Ther Res. 1991;

: 10-15.

. Dooley M, Spencer CM, Dunn CJ. Aceclofenac: a reappraisal of its use in the management of pain and rheumatic disease. Drugs. 2001; 61:1351-78.

. Rogers JC, Irrgang JJ. Measures of adult lower extremity functions. Arithritis Care Res. 2003; 49(5S): S67-S84.

. Desai P, Patel S, Shah R, et al. A comprehensive evaluation of rationality of cough and cold medicines available in Indian market. J Indian Med Assoc. 2013 Feb; 111(2):94-8.

. Goswami N, Gandhi A, Patel P, et al. An evaluation of knowledge, attitude and practices about prescribing fixed dose combinations among resident doctors. Perspect Clin Res. 2013 Apr; 4(2):130-5.

. Chopra A, Patil J, Bilampelly V, et al. Prevalance of rheumatic disease in rural population in Western India: A WHO-ILAR-COPCORD study. J Assoc physicians India. 2001; 49: 240-46.

. Gillian AH, Samra M, Tetyana K, et al. Measures of adult pain: Visual Analog Scale Pain (VAS pain), Numeric Rating Scale (NRS pain), McGill Pain Questionnaire (MPQ), Chronic Pain Grade Scale (CPGS), Short Form-36 Bodily Pain Scale (SF-36 BPS), and Measure of Intermittent and Constant Osteoarthritis Pain (ICOAP).Arthritis & Research.2011; 63(11): 240-252.

. Kersten P, Ayse A, Kucukdeveci, et al. The use of the visual analogue scale (VAS) in rehabilitation outcomes Rehabil Med.2012; 44: 609-610.

. Salaffi F, Stancati A, Silvestri CA, et al. Minimal clinically important changes in chronic musculoskeletal pain intensity measured on a numerical rating scale. Eur J Pain.2004; 8: 283-91.

. Joyce CR, Zutshi DW, Hrubes VF, et al. Comparison of fixed interval and visual analogue scales for rating chronic pain. Eur J Clin Pharmacol. 1975; 8: 415-20.

. Ferraz MB, Quaresma MR, Aquino LR, et al. Reliability of pain scales in the assessment of literate and illiterate patients with rheumatoid arthritis. J.Rheumatol. 1990; 17: 1022-4.

. Bellamy N, Buchanan WW. A preliminary evaluation of the dimensionality and clinical importance of pain and disability in osteoarthritis of the hip and knee. Clin Rheumatol. 1986; 5: 231-41.

. Ehrich EW, Davies GM, Watson DJ, et al. Minimal perceptible clinical improvement with the Western Ontario and McMaster Universities Osteoarthritis Index Questionnaire and Global Assessment in patients with Osteoarthritis. J. Rheumatol. 2000; 27(11): 2635-41.

. Mobasheri Al. The Future of Osteoarthritis Therapeutics: Targeted Pharmacological Therapy. CurrRep. 2013; 15(364): 1-13

. Joern W, Micheal P, Klaus U, et al. The Epidemiology, Etiology, Diagnosis and Treatment of Osteoarthritis of the knee. Dtsch Arztebl int. 2010; 107(9): 152-62.

. Johanne MP, Jean PP, et al. Effects of diacerein at molecular level in the osteoarthritis disease process. Therapeutic Advances in Musculoskeletal Disease.2010; 2(2): 95-104.

. Sreedhar D, Subramanian G, Udupa N. Combination drugs: are they rational? Curr Sci 2006; 91: 406.

. Chandler S. Gautam & Lekha S. Fixed dose drug combinations (FDCs): rational or irrational: a view point. Br J Clin Pharmacol. 2008; 65:5 / 795–79.

. Poudel A, Palaian S, Shankar PR, et al. Irrational fixed dose combinations in Nepal: need for intervention. Kathmandu Univ Med J (KUMJ). 2008 Jul-Sep; 6(23):399-405.

. Sripal B, Gayathri K, Sanobar P, et al. Fixed- dose Combinations improves Medication Compliance: A Meta Analysis. The American Journal of Medicine. 2007; 120: 713-19.

. Bhavik D, Amit K, Rakeshkumar R. A randomized, active controlled, clinical trial to assess the efficacy and safety of Celecoxib+ Diacerein fixed dose combination in adult Indian patients- suffering from Osteoarthritis. Innovative Journal of Medical & Health Science. 2012; 2: 31-34.

. Torri G, Vignati C, Agrifoglio E, et al. Aceclofenac versus Piroxicam in the management of Osteoarthritis of the knee: A double blind controlled study. Current Therapeutic Research.1994; 55(5): 576-583.

. Patil PR, Jaida J, Palani A, et al. A comparative study of efficacy and safety of Diclofenac and Aceclofenac in the treatment of Osteoarthritis patients. Journal of Drug Delivery and Therapeutics. 2012; 2(4): 139-143.

. Kurubaran G, Michael JM, Vasudeva MCR, et al. Level and Determinants of knowledge of Symptomatic Knee Osteoarthritis among Railway Workers in Malaysia. Biomed Research International.2014; Article ID 370273: 1-9.

. Awan MMY, Ahmad I, Aziz A. Efficacy and safety of Aceclofenac in the treatment: A randomized double –blind comparative clinical trial versus Diclofenac. Professional Med J.2014; 21(3): 471-476.

. Pham T, Henanff A, Ravaud Ph et al. Evaluation of the symptomatic & structural efficacy of a new hyaluronic acid compound, NRD101, in comparison with Diacerein & placebo in a year randomized controlled study in symptomatic knee Osteoarthritis. Ann Rheum Dis. 2004; 63: 1611-17.

. Marcia UDR, Gustavo CDC, Alexandre FP. Current concepts in osteoarthritis. Acta Ortop Bras. 2013; 2 (12): 120-2.

. Guaida EB, Ivorra JR, Mola EM, et al. Aceclofenac vs. paracetmol in the management of symptomatic Osteoarthritis of the knee: a double blind 6-week randomized controlled trail. Osteoarthritis and Cartilage. 2007; 15(7): 900-908.

. Zhuo Q, Yang W, Chen J, et al. Metabolic syndrome meets osteoarthritis. Nat Rev Rheumatol.

. Andrianakos AA, Kontelis LK, Karamitsos DG, et al. Prevalance of symptomatic knee, hand and hip osteoarthritis in Greece. The ESORDIG study. Journal of Rheumatology. 2006; 33(12): 2507-2514.

. Sharma A, Rathod R, Baliga VP. An open prospective study on post marketing evaluation of the efficacy and tolerability of Diacerein in Osteoarthritis of the knee (DOK).J Indian Med Assoc.2008; 106(1): 54-58.

. Brahmachari B, Chatterjee S, Ghosh A. Efficacy and Safety of Diacerein in early Osteoarthritis: a randomized placebo-controlled trail. Clin Rheumatol. 2009; 28(10).

. Geiter LJ, O Brien RJ, Combs DL, et al. Preliminary results of an evaluation of a combination tablet of isoniazid, rifampin and pyrazinamide.Tubercle.1987; 68(2): 41-46.

. Su WJ, Perng RP. Fixed dose combination chemotherapy (Rifater/Rifinah) for active pulmonary tuberculosis in Taiwan: a two year follow-up. Int J Tuberc Lung Dis.2002; 6: 1029-101032.

. Eron JJ, Yetzer ES, Ruane PJ, et al. Efficacy, safety and adherence with twice – daily combination lamivudine/zidovudine tablet formulation, plus a protease inhibitor, in HIV infection. AIDS. 2000; 14:671-681.

. Taylor AA, Shoheiber O. Adherence to antihypertensive therapy with fixed dose amlodipine besylate/benazepril HCL versus comparable component–based therapy. Congest Heart Fail. 2003; 9: 324-332.

. Melikian C, White TJ, Vanderplas A, et al. Adherence to oral antidiabetic therapy in a managed Care organization: a comparison of monotherapy, combination therapy and fixed dose Combination therapy. Clin Ther.2002; 24: 460-467.

. Paul S, Das N, Ghosh S. The effects of Aceclofenac & nabumetone in Osteoarthritis. JNMA J Nepal Med Assoc. 2009; 48(174): 121-5.

. Ward DE, Veys EM, Bowdler JM, Roma J. Comparison of Aceclofenac with diclofenac in the treatment of Osteoarthritis. Clin Rheumatol. 1995; 14(6): 656-62.

. Pareek A, Chandurkar N, Oak J, et al. Efficacy & safety of Aceclofenac in the treatment of osteoarthritis double-blind comparative clinical trial versus diclofenac-an Indian experience. Curr Med Res Opin. 2006; 22(5): 977-88.

. Pareek A, Chandurkar N. Comparison of gastrointestinal safety & tolerability of Aceclofenac with diclofenac: a multicentreic, randomized, double blind study in patients with osteoarthritis. Curr Med Res Opin. 2013; 29(7): 849-59.

. Klair JP. A comparative Study of efficacy and Tolerability of Ibuprofen Vs Aceclofenac in Osteoarthritis of Knee Joint. Annals of Medicine & Healthcare. 2009: 236.

. Soria MAA, Largo R, Santilana J, et al. Long term NSAID treatment inhibits COX-2 synthesis in the synovial membrane of patients with Osteoarthritis: differential proinflammatory cytokine profile between Celecoxib and Aceclofenac. Annals of Rheumatic diseases. 2006; 65: 998-1005.

. Hinz B, Auge D, Rau T, et al. Simultation determination of Aceclofenac and three of its metabolites in human plasma by high –performance liquid chromatography. Biomed Chromatogr.2003; 17: 268-75.

. Gowda KV, Rajan DS, Mandal U, et al. Evaluation of bioequivalence of two formulations containing 100 milligrams of Aceclofenac. Drug Dev Ind Pharm.2006; 32: 1219-25. `

. Loitongbam LSS, Handa G, Sing U, et al. Efficacy of Diacerein in the treatment of Osteoarthritis of Knee.IJPMR.2013; 24(4): 92-8.

. Boileau C, Tat SK, Pelletier JP, et al. Diacerein inhibits the synthesis of resorptive enzymes and reduces osteoclastic differentiation/survival in osteoarthritic subchondral bone: a possible mechanism for a protective effect against subchondral bone remodelling. Arthritis Res Ther. 2008; 10 R71.

. Pelletier JP, Lajeunesse D, Reboul P, et al. Diacerein reduces the excess synthesis of bone remodelling factors by human osteoblasts cells from osteoarthritic subchondral bone. J Rheumatol. 2001; 28: 814-24.

. Kwan TS, Pelletier JP, Lajeunesse D, et al. The differential expression of osteoprotegerin (OPG) and receptor activator of nuclear factor kappa B ligand (RANK) in human osteoarthritic subchondral bone osteoblasts is an indicator of the metabolic state of these disease cells. Clin Exp Rheumatol.2008; 26:295-304.

. Pareek A, Chandurkar N, Gupta A, et al. Efficacy & safety of Aceclofenac-CR & Aceclofenac in the treatment of knee osteoarthritis: a 6-week, comparative, randomized, multicentric, double-blind study. J Pain. 2011; 12(5): 546-53.

. Pelletier JP, Yaron M, Harooui B, et al. Efficacy & safety of Diacerein in Osteoarthritis of the knee: a double- blind placebo controlled trail. The Diacerein study group .Arthritis Rheum. 2000; 43: 2339-48.

. Bartel EM, Bliddal H, Schondorff PK, et al. Symptomatic efficacy and safety of Diacerein in the treatment of Osteoarthritis: a meta- analysis of randomized placebo-controlled trails. Osteoarthritis and Cartilage. 2009; 18(3): 289-296.




DOI: http://dx.doi.org/10.7439/ijpr.v7i5.4168

Article Metrics

Metrics Loading ...

Metrics powered by PLOS ALM

Refbacks

  • There are currently no refbacks.




Copyright (c) 2017 International Journal of Pharmacological Research

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.