Treatment of rheumatoid arthritis: csDMARDS versus bDMARDS. Prospective study to evaluate disease activity


rheumatoid arthritis
disease activity
biological therapy

How to Cite

Boyadzhieva, V., Stoilov, N., Ivanova, M. and Stoilov, R. 2019. Treatment of rheumatoid arthritis: csDMARDS versus bDMARDS. Prospective study to evaluate disease activity. Rheumatology (Bulgaria). 27, 1 (Apr. 2019), 3-15. DOI:


The assessment of disease activity is an essential component in the selection of therapeutic approach for the prevention of disability of patients with RA. The current study was conducted to evaluate the disease activity in patients on csDMARDs and bDMARDs after 6 months to 1-year of treatment and to determine whether the benefits of different therapies were sustained over time. For the purpose of the study were selected 220 patients with a mean age 55.05 ± 10.63 SD years, meeting the 1987 ACR classification criteria for RA. Patients were stratified according to treatment regimens into 2 age-matched treatment groups: 96 on csDMARDs and 124 on bDMARD therapy. Patient‘s assessment of disease related pain, global health and physician assessment of global health was made by visual analogue scale (VAS) – 100 mm. Disease activity was the primary outcome domain. Independent joint assessor evaluated 28 joints on baseline, 6th and 12th month of the follow-up period. C-reactive protein (CRP) was used to measure the infl ammation process. DAS28-CRP, CDAI and SDAI were calculated according to the standard formulas. Comparison was performed by analysis variance ANOVA. On baseline, patients on bDMARDs had a significantly higher mean time-averaged 28-joint disease activity score (5.03 ± 0.84 SD vs. 4.35 ± 1.20 SD, p < 0,001), CDAI (25.06 ± 7.32 SD vs. 20.83 ± 10.53 SD, p < 0.001) and SDAI (28.27 ± 8.74 SD vs. 23.19 ± 11.89 SD, p < 0.001) compared to those on csDMARDs. On the 6th month in both groups (bDMARDS and csDMARDs) we found significant decrease in mean DAS28 (p < 0.001, p < 0.001), although no significant difference in disease activity between the groups was measured by this indicator (3.75 ± 2.49 SD vs 3.90 ± 1.10 SD, p = 0.566). Patients on bDMARDs had significantly lower disease activity compared to those on csDMARDs after 6th and 12th month of treatment assessed by CDAI (13.43 ± 4.98 SD vs 16.81 ± 9.94 SD, p = 0.001; 8.65 ± 4.53 SD vs 15.86 ± 10.02 SD, p < 0.001), and SDAI (14.63 ± 5.42 SD vs 18.38 ± 10.49 SD, p < 0.001; 9.39 ± 4.92 SD vs 16.79 ± 10.5 SD, p < 0.001). Unlike results reported by DAS28-CRP which showed no change between the 6th and 12th month in patients receiving csDMARDs (3.90 ± 1.10 SD, 3.82 ± 1.12 SD, p = 0.156), we observed a statistically significant difference in all three time intervals (0, the 6th, 10th month) of the follow up period regarding to CDAI and SDAI. After a year prospective follow-up, therapy with biologic DMARDs results in sustained suppression – minimal disease activity assessed by DAS28-CRP, CDAI and SDAI, compared to patients receiving DMARDs who had moderate disease activity according to these tools. The therapy with bDMARDs was superior to csDMARDs therapy for suppressing disease activity (assessed by DAS28-CRP, CDAI and SDAI) of rheumatoid arthritis (RA) on the 6th and 12th month of the follow-up period.


  1. McInnes IB, Schett G. The pathogenesis of rheumatoid arthritis. N Engl J Med. (2011) 365:2205-19.
  2. Lansbury J. Quantitation of the activity of rheumatoid arthritis. A method for summation of the systemic indices of rheumatoid activity. Am J Med Sci 1956;232:300-10.
  3. Prevoo ML, Van‘t Hof MA, Kuper HH et al. Modifi ed disease activity scores that include twenty-eight-joint counts. Development and validation in a prospective longitudinal study of patients with rheumatoid arthritis. Arthritis Rheum. 1995, 38:44-8.
  4. Anderson J, Caplan L, Yazdany J et al. Rheumatoid Arthritis Disease Activity Measures: American College of Rheumatology Recommendations for Use in Clinical Practice. Arthritis Care Res (Hoboken). 2012; 64(5): 640-647.
  5. Стоилов Р, Иванова М. Индекси за оценка на болестна- та активност при ревматоидния артрит и анкилозиращия спондилит. Актуални проблеми в ревматологията. София, 2006, 14;53-60.
  6. Singh JA, Furst DE, Bharat A, et al. American College of Rheumatology recommendations for the use of disease-modifying anti-rheumatic drugs and biologic agents in the treatment of rheumatoid arthritis. Arthritis Care Res (Hobo- ken), 2012;64:625-39.
  7. Salaffi F, Ciapetti A. Clinical disease activity assessments in rheumatoid arthritis. Int. J. Clin. Rheumatol. (2013) 8(3), 347-360.
  8. Kvien TK, Heiberg MS, Lie. E et. al. A Norwegian DMARD register: Prescriptions of DMARDs and biological agents to patients with inflammatory rheumatic diseases. Clin Exp Rheumatol 2005; 23 (Suppl. 39): S188-S194.
  9. Lipsky PE, Van Der Heijde DM, ST Clair EW et al. Infliximab and methotrexate in the treatment of rheumatoid arthritis. Anti–Tumor Necrosis Factor Trial in Rheumatoid Arthritis with Concomitant Therapy Study Group. N Engl J Med 2000; 343: 1594-602.
  10. Klareskog L, Van Der Heide, De Jager JP et al. Therapeutic effect of the combination of etanercept and methotrexate compared with each treatment alone in patients with rheumatoid arthritis: double-blind randomised controlled trial. Lancet 2004; 363: 675-81.
  11. Keystone EC, Kavanaugh AF, Sharp JT et al. Radiograph- ic, clinical, and functional outcomes of treatment with adalimumab (a human anti-tumor necrosis factor mono- clonal antibody) in patients with active rheumatoid arthritis receiving concomitant methotrexate therapy: a randomized, placebo-controlled, 52-week trial. Arthritis Rheum 2004; 50: 1400-11.
  12. Bathon JM, Martin RW, Fleischmann RM et al. A comparison of etanercept and methotrexate in patients with early rheumatoid arthritis. N Engl J Med 2000; 343: 1586- 93.
  13. Genovese MC, Bathon JM, Martin RW et al. Etanercept versus methotrexate in patients with early rheumatoid arthritis: twoyear radiographic and clinical outcomes. Arthritis Rheum 2002; 46: 1443-50.
  14. Van De Putte LB, Atkins C, Malaise M et al. Efficacy and safety of adalimumab as monotherapy in patients with rheumatoid arthritis for whom previous disease modifying anti- rheumatic drug treatment has failed. Ann Rheum Dis 2004; 63: 508-16.
  15. Clairew ST, Van Der Heijde DM, Smolen J S et al. Combination of infliximab and methotrexate therapy for early rheumatoid arthritis: a randomized, controlled trial. Arthritis Rheum 2004; 50: 3432-43.
  16. Choi HK, Seeger JD, Kuntz KM. A cost-effectiveness analysis of treatment options for patients with methotrexate-resistant rheumatoid arthritis. Arthritis Rheum. 2000;43;2316-27.
  17. Hockley T, Costa-Font J. A Common Disease with Uncommon treatment. European Guideline Variations and access to innovative therapies for Rheumatoid Arthritis. 2012.
  18. Pease, C et al. Comparison of Anti-TNF Treatment Initiation in Rheumatoid Arthritis Databases Demonstrates Wide country variability in patient parameters at initiation of anti-TNF therapy. Seminars in arthritis and rheumatism.2011;41(1), 81-89.
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