Assessing the impact of methotrexate, hydroxychloroquine, and their combination in rheumatoid arthritis: efficacy, safety, and cost analysis with vitamin D3 and BMI


  • Amanjot Kaur Pharmacology Department, Adesh institute of medical sciences and research, Bathinda
  • Amandeep Singh Pharmacology Department, Shri Atal Bihari Vajpayee Medical College, Haryana
  • Amit Varma Medicine Department, Shri Guru Ram Rai Medical College, Dehradun



Average cost-effective ration, Adverse effects, Body Mass Index, Combination therapy, Vitamin D3


Background: A chronic, symmetrical & inflammatory disease, which affects small joints and later progresses to involve large joints. To promote remission and control further joint destruction, disease modifying ant rheumatic drugs are used. The role of low Vitamin D3 and High BMI have been found in pathogenesis of RA. Methodology: The study was designed by Department of pharmacology and patients were enrolled from department of medicine. This was an open label; prospective study. After obtaining, informed written consent, the subjects were randomized in three groups, Group 1-Methotrexate 7.5-15mg once a week, Group 2 - Hydroxychloroquine 200mg BD and Group 3-Methotrexate 7.5mg once a week Plus HCQ 200mg OD. The Vitamin D3 levels and Body mass index was assessed at first visit. The quality of life was assessed using DAS-28/CRP, RAPID-3 Score. Average cost-effective ratio was also calculated. The adverse effects were also assessed using WHO-UMC causality assessment. The statistical analysis of the data Graph pad insta version 3.1 was used, p-value <0.05 was considered statistically significant. Results: The mean changes in DAS28/CRP and RAPID-3 between baseline & 16 weeks was highly significant (p<0.0001) in all groups. Vitamin D3 levels at baseline was 19.14±0.42, 19.86±0.67 and 19.52±0.98 in all groups respectively. Conclusion: The vitamin D3 levels were in the lower limit and BMI was raised in almost all the patients at first visit. The efficacy of combination therapy is found to be better when given at initial stages of RA patients


Download data is not yet available.


Bullock J, Rizvi SAA, Salen AM, Ahmed SS, Do DP, Ansari RA et al. Rheumatoid arthritis: A brief overview of the treatment. Medical Principles and Practice, 27,501-507 (2018).

Radu AF, Bungau SG. Management of Rheumatoid Arthritis: An Overview. Cells, 10(11), 2857(2021).

Adami, G, Viapiana O, Rossini M, Orsolini G, Bertoldo E, Giollo A et al. Association between environmental air pollution and rheumatoid arthritis flares. Rheumatology, 2 60, 4591–4597 (2021).

Wells PM, Williams FMK, Matey-Hernandez M.L, Menni C, Steves CJ. RA and the microbiome: Do host genetic factors provide the link? J. Autoimmun., 99, 104–115 (2019).

Andrew E, Rosenberg MD. In Bones. In Joints and Soft tissue tumors. In Kumar, Abbas, Fausto Robbins & Cotran Pathologic Basis of Disease .7th edition Elsevier Saunders: p1305-9

Mohamed SR, Neseem NO, Metwally SS, El-Kady BA. Diagnostic value and clinical significance of anti-carbamylated protein (anti-CarP) antibodies in Egyptian patients with rheumatoid arthritis. Egypt. Rheumatol, 42, 1–4 (2020).

Singh JA, Saag KG, Bridges SL Jr, Akl EA, Bannuru RR, Sullivan MC et al. American College of Rheumatology. 2015 American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis. Arthritis Care Res (Hoboken), 68(1), 1-25 (2016).

Aletaha D Smolen JS. Diagnosis and management of rheumatoid arthritis: A review. JAMA, 320(13),1360-1372 (2018).

van der Heijde DM, van 't Hof M, van Riel PL, van de Putte LB. Development of a disease activity score based on judgment in clinical practice by rheumatologists. J Rheumatol, 20(3):579-581 (1993).

Okamura JM, Miyagi JM, Terada K, Hokama Y. Potential clinical applications of C-reactive protein. J Clin Lab Anal, 4(3), 231-235 (1990).

Dessein PH, Joffe BI, Stanwix AE. High sensitivity C-reactive protein as a disease activity marker in rheumatoid arthritis. J Rheumatol, 31, 1095-1097 (2004).

Agca R, Heslinga SC, Rollefstad S. EULAR recommendations for cardiovascular disease risk management in patients with rheumatoid arthritis and other forms of inflammatory joint disorders: 2015/2016 update. Ann Rheum Dis, 76(1), 17-28 (2017).

Beyan E, Beyan C, Demirezer A, Ertuğrul E, Uzuner A. The relationship between serum ferritin levels and disease activity in systemic lupus erythematosus. Scand J Rheumatol, 32(4), 225-228(2003).

Arvidson NG, Larsson A, Larsen A. Disease activity in rheumatoid arthritis: fibrinogen is superior to the erythrocyte sedimentation rate. Scand J Clin Lab Invest, 62(4), 315-319 (2002).

Guan Y, Hao Y, Guan Y, Bu H, Wang H. The Effect of Vitamin D Supplementation on Rheumatoid Arthritis Patients: A Systematic Review and Meta-Analysis. Front Med (Lausanne), 30(7), 596007(2020).

Gewurz H, Mold C, Siegel J, Fiedel B. C-reactive protein and the acute phase response. Adv Intern Med, 27, 345-372 (1982).

Cramp F. The role of non-pharmacological interventions in the management of rheumatoid arthritis related fatigue. Rheumatology, 58, v22-v28 (2019).

Smolen JS, Landewé RBM, Bijlsma JWJ. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2019 update. Ann Rheum Dis, 79(6), 685-699 (2020).

Steultjens EM, Dekker J, Bouter LM, van Schaardenburg D, van Kuyk MA, van den Ende CH. Occupational therapy for rheumatoid arthritis: a systematic review. Arthritis Rheum, 47(6), 672-685 (2002).

Guo Q, Wang Y, Xu D, Nossent J, Pavlos NJ, Xu J. Rheumatoid arthritis: pathological mechanisms and modern pharmacologic therapies. Bone Res, 6, 15 (2018).

Feng X, Xu X, Shi Y, Liu X, Liu H, Hou H et al. Body Mass Index and the Risk of Rheumatoid Arthritis: An Updated Dose-Response Meta-Analysis. Biomed Res Int, 3579081 (2019).

Grennan DM, Gray J, Loudon J, Fear S. Methotrexate and early postoperative complications in patients with rheumatoid arthritis undergoing elective orthopaedic surgery. Ann Rheum Dis, 60(3), 214-217 (2001).

Ometto F, Botsios C, Raffeiner B. Methods used to assess remission and low disease activity in rheumatoid arthritis. Autoimmun Rev, 9(3), 161-164 (2010).

Köhler BM, Günther J, Kaudewitz D, Lorenz HM. Current therapeutic options in the treatment of rheumatoid arthritis. J Clin Med, 8(7), 938 (2019).

Salaffi F, Sarzi-Puttini P, Girolimetti R, Atzeni F, Gasparini S, Grassi W. Health-related quality of life in fibromyalgia patients: a comparison with rheumatoid arthritis patients and the general population using the SF-36 health survey. Clin Exp Rheumatol, 27, S67-S74 (2009).

Lee EB, Fleischmann R,Hall S, Wilkinson B, Bradley JD,Gruben D. Tofacitinib versus methotrexate in rheumatoid arthritis. NEJM, 370, 2377-86 (2014).

Liao KP, Alfredsson L, Karlson EW. Environmental influences on risk for rheumatoid arthritis. Curr Opin Rheumatol, 21(3), 279-83 (2009).

American College of Rheumatology Subcommittee on Rheumatoid Arthritis Guidelines. Guidelines for the management of rheumatoid arthritis: 2002 Update. Arthritis Rheum, 46(2), 328-346 (2002).

Goma SH, Razek MRA, Abdelbary NM. Impact of rheumatoid arthritis on the quality of life and its relation to disease activity. Egyptian Rheumatology and Rehabilitation, 46, 304-312 (2019).

Shashikumar NS, Shivamurthy MC, Chandrashekara S. Evaluation of efficacy of combination of methotrexate and hydroxychloroquine with leflunomide in active rheumatoid arthritis. Indian J Pharmacol, 42(6), 358-61 (2010).

Pincus T, Swearingen CJ, Bergman MJ. RAPID3 (Routine Assessment of Patient Index Data) on an MDHAQ (Multidimensional Health Assessment Questionnaire): agreement with DAS28 (Disease Activity Score) and CDAI (Clinical Disease Activity Index) activity categories, scored in five versus more than ninety seconds. Arthritis Care Res (Hoboken), 62(2), 181-189 (2010).

Koumantaki Y, Giziaki E, Linos A, Kontomerkos A, Kaklamanis P,Vaiopolous G et al. Family history as a risk factor for rheumatoid arthritis: a case-control study. J Rheumatol, 24(8), 1522-1526 (1997).

Lipsky PE, Desiree MFM, Heijde VD, St. Clair W, Daniel E, Ferdinand C. Infliximab and Methotrexate in the treatment of rheumatoid arthritis. NEJM, 343,1594-1602 (2000).

Pavelka K Jr, Sen KP, Pelísková Z, Vácha J, Trnavský K. Hydroxychloroquine sulphate in the treatment of rheumatoid arthritis: a double-blind comparison of two dose regimens. Ann Rheum Dis, 48(7), 542-546 (1989).

Bathon JM, Martin RW, Fleischmann RM. A comparison of etanercept and methotrexate in patients with early rheumatoid arthritis. N Engl J Med, 344(1), 76 (2001).

Mathur R, Singh H, Arya S, Singh V. Comparative evaluation of efficacy of Leflunomide versus combination of methotrexate & hydroxychloroquine in patients with Rheumatoid Arthritis. Indian Journal of Rheumatology, 11(2), 86-90 (2016).

Song Y, Zhu LA, Wang SL, Leng L, Bucala R, Lu LJ. Multi-dimensional health assessment questionnaire in China: reliability, validity and clinical value in patients with rheumatoid arthritis. PLoS One, 9(5), 97952 (2014).

Pollard L, Choy EH, Scott DL. The consequences of rheumatoid arthritis: quality of life measures in the individual patient. Clin Exp Rheumatol, 23, S43-S52 (2005).

Brook A, Corbett M. Radiographic changes in early rheumatoid disease. Ann Rheum Dis, 36(1), 71-3 (1977).

Krishnan S, Balan CS, Mohamedali SP. A cost-effective analysis of various disease modifying anti-rheumatic drugs for patients with Rheumatoid Arthritis. Int J Basic Clin Pharmacol, 7, 1153-9 (2018).



How to Cite

Kaur, A., Singh, A. ., & Varma, A. . (2023). Assessing the impact of methotrexate, hydroxychloroquine, and their combination in rheumatoid arthritis: efficacy, safety, and cost analysis with vitamin D3 and BMI. Journal of Applied Pharmaceutical Research, 11(2), 32-39.