The inflammatory disease burden at presentation is a good indicator of early LDA/remission: A retrospective study
DOI:
https://doi.org/10.15305/ijrci/v5i1/214Keywords:
Rheumatoid arthritis, early remission, DAS28CRP, predictive equation, logistic regressionAbstract
Background: Factors predicting early response to treatment in rheumatoid arthritis (RA) assist in optimizing treatment strategies. DAS28CRP is routinely used to measure treatment response, whereas the role of associated biomarkers has not been thoroughly assessed.
Objective: To examine the clinical utility of baseline demographic, clinical, and immunological parameters as predictors of early response to treatment in RA patients. To develop an empirical equation to assess the probability of early remission.
Methods: We included data from newly diagnosed RA patients who fulfilled ACR-EULAR 2010 classification criteria in an exploratory, retrospective observational study. Patients’ initial assessment and follow-up data were collected. Variables were assessed by t-test or Mann-Whitney test as appropriate, univariate regression and receiver operating characteristic (ROC) curve. A predictive equation was developed using multiple logistic regression. Model accuracy evaluated by ROC curve. The bootstrap procedure was used to assess internal validity.
Results: The study included 159 patients after screening for inclusion and exclusion criteria. A multivariate logistic regression with age, hemoglobin percentage (Hb%), neutrophil-to-lymphocyte ratio (NLR) and DASCRP was performed. The discriminatory ability of the predictive model was fair, area under the curve (AUC) = 0.711 (95% CI- 0.630-0.792) with P-value <0.001 and calibration slope of 0.98. The corresponding sensitivity and specificity noted were 49.2%, and 78.7%. The bias-corrected C index was 0.683.
Conclusion: This multivariate logistic equation improves on currently recommended methods of screening for remission. The baseline DAS28CRP score is a strong predictor and inclusion of additional factors like NLR and Hb% contribute to prediction. Further studies in a large cohort could improve and confirm these results.
References
Combe B, Landewe R, Lukas C, et al. EULAR recommendations for the management of early arthritis: report of a task force of the European Standing Committee for International Clinical Studies Including Therapeutics (ESCISIT). Ann Rheum Dis. 2007;66(1):34-45. doi:10.1136/ard.2005.044354.
Mednet - CME, CHE | Rapid Treatment Response in Rheumatoid Arthritis: A Valuable Indicator of Reduced Risk of Joint Damage. http://www.mednet.ca/en/report/rapid-treatment-response-in-rheumatoid-arthritis.html. Accessed October 31, 2015.
Rantalaiho V, Kautiainen H, Järvenpää S, et al. Failure in long term treatment is rare in actively treated patients with rheumatoid arthritis, but may be predicted by high health assessment score at baseline and by residual disease activity at 3 and 6 months: the 5-year followup results of the randomized clinical NEO-RACo trial. J Rheumatol. 2014;41(12):2379-2385. doi:10.3899/jrheum.140267.
Kuriya B, Xiong J, Boire G, et al. Earlier time to remission predicts sustained clinical remission in early rheumatoid arthritis--results from the Canadian Early Arthritis Cohort (CATCH). J Rheumatol. 2014;41(11):2161-2166. doi:10.3899/jrheum.140137.
Ma MHY, Ibrahim F, Walker D, et al. Remission in early rheumatoid arthritis: predicting treatment response. J Rheumatol. 2012;39(3):470-475. doi:10.3899/jrheum.110169.
Mierau M, Schoels M, Gonda G, Fuchs J, Aletaha D, Smolen JS. Assessing remission in clinical practice. Rheumatology (Oxford). 2007;46(6):975-979. doi:10.1093/rheumatology/kem007.
Gramling A, O’Dell JR. Initial management of rheumatoid arthritis. Rheum Dis Clin North Am. 2012;38(2):311-325. doi:10.1016/j.rdc.2012.05.003.
Goekoop-Ruiterman YPM, de Vries-Bouwstra JK, Allaart CF, et al. Clinical and radiographic outcomes of four different treatment strategies in patients with early rheumatoid arthritis (the BeSt study): a randomized, controlled trial. Arthritis Rheum. 2005;52(11):3381-3390. doi:10.1002/art.21405.
Grigor C, Capell H, Stirling A, et al. Effect of a treatment strategy of tight control for rheumatoid arthritis (the TICORA study): a single-blind randomised controlled trial. Lancet. 2004;364(9430):263-269. doi:10.1016/S0140-6736(04)16676-2.
Schipper LG, Fransen J, den Broeder AA, Van Riel PLCM. Time to achieve remission determines time to be in remission. Arthritis Res Ther. 2010;12(3):R97. doi:10.1186/ar3027.
Verstappen SMM, van Albada-Kuipers GA, Bijlsma JWJ, et al. A good response to early DMARD treatment of patients with rheumatoid arthritis in the first year predicts remission during follow up. Ann Rheum Dis. 2005;64(1):38-43. doi:10.1136/ard.2003.014928.
Emery P, Salmon M. Early rheumatoid arthritis: time to aim for remission? Ann Rheum Dis. 1995;54(12):944-947.
Smolen JS, Landewé R, Breedveld FC, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs. Ann Rheum Dis. 2010;69(6):964-975. doi:10.1136/ard.2009.126532.
Singh JA, Furst DE, Bharat A, et al. 2012 update of the 2008 American College of Rheumatology recommendations for the use of disease-modifying antirheumatic drugs and biologic agents in the treatment of rheumatoid arthritis. Arthritis Care Res (Hoboken). 2012;64(5):625-639. doi:10.1002/acr.21641.
Madsen OR. Is DAS28-CRP with three and four variables interchangeable in individual patients selected for biological treatment in daily clinical practice? Clin Rheumatol. 2011;30(12):1577-1582. doi:10.1007/s10067-011-1847-6.
Steyerberg EW, Harrell FE, Borsboom GJJM, Eijkemans MJC, Vergouwe Y, Habbema JDF. Internal validation of predictive models. Journal of Clinical Epidemiology. 2001;54(8):774-781. doi:10.1016/S0895-4356(01)00341-9.
S Chandrashekara. Quantification of inflammation: Needs and challenges. Internet Journal of Rheumatology and Clinical Immunology. 2014;2(S1). doi:10.15305/ijrci/v2iS1/91.
Venkatraghavan L, Tan TP, Mehta J, Arekapudi A,
Govindarajulu A, Siu E. Neutrophil Lymphocyte Ratio as a predictor of systemic inflammation - A cross-sectional study in a pre-admission setting. F1000Research. May 2015. doi:10.12688/f1000research.6474.1.
Fu H, Qin B, Hu Z, et al. Neutrophil- and platelet-to-lymphocyte ratios are correlated with disease activity in rheumatoid arthritis. Clin Lab. 2015;61(3-4):269-273.
Gangat N, Wolanskyj AP. Anemia of Chronic Disease. Seminars in Hematology. 2013;50(3):232-238. doi:10.1053/j.seminhematol.2013.06.006.
N G, U T, Ag J, et al. Inflammatory patterns in rheumatoid arthritis estimated by the number of swollen and tender joints, the erythrocyte sedimentation rate, and hemoglobin: long term course and association to radiographic progression. J Rheumatol. 2000;27(1):47-57.
Thorne C, Bensen WG, Choquette D, et al. Effectiveness and Safety of Infliximab in Rheumatoid Arthritis: Analysis From a Canadian Multicenter Prospective Observational Registry. Arthritis Care & Research. 2014;66(8):1142-1151. doi:10.1002/acr.22290.
Hetland ML. Modern treatment strategies in rheumatoid arthritis. Dan Med Bull. 2011;58(11):B4320.
Ten Klooster PM, Vonkeman HE, Oude Voshaar MAH, Siemons L, van Riel PLCM, van de Laar MAFJ. Predictors of satisfactory improvements in pain for patients with early rheumatoid arthritis in a treat-to-target study. Rheumatology (Oxford). 2015;54(6):1080-1086. doi:10.1093/rheumatology/keu449.
Cannon GW, Wang BC, Park GS, Koenig A, Collier DH, Keystone EC. Remission in rheumatoid arthritis patients treated with etanercept monotherapy: clinical practice and clinical trial experience. Clin Exp Rheumatol. 2013;31(6):919-925.
Jawaheer D, Messing S, Reed G, et al. Significance of sex in achieving sustained remission in the consortium of rheumatology researchers of North America cohort of rheumatoid arthritis patients. Arthritis Care Res (Hoboken). 2012;64(12):1811-1818. doi:10.1002/acr.21762.
Chandrashekara S, Priyanka BU. Remission in rheumatoid arthritis by different criteria does not converge over the inflammatory markers. Int J Rheum Dis. 2013;16(3):291-296. doi:10.1111/1756-185X.12091.
Contreras-Yáñez I, Rull-Gabayet M, Pascual-Ramos V. Early disease activity suppression and younger age predict excellent outcome of recent-onset rheumatoid arthritis patients treated with conventional disease modifying anti-rheumatic drugs. Clin Exp Rheumatol. 2012;30(3):402-408.
Salgado E, Maneiro JR, Carmona L, Gómez-Reino J. Rheumatoid factor and response to TNF antagonists in rheumatoid arthritis: systematic review and meta-analysis of observational studies. Joint Bone Spine. 2014;81(1):41-50. doi:10.1016/j.jbspin.2013.04.004.
Sakthiswary R, Shaharir SS, Mohd Said MS, Asrul AW, Shahril NS. IgA rheumatoid factor as a serological predictor of poor response to tumour necrosis factor α inhibitors in rheumatoid arthritis. Int J Rheum Dis. 2014;17(8):872-877. doi:10.1111/1756-185X.12443.
Gossec L, Dougados M, Goupille P, et al. Prognostic factors for remission in early rheumatoid arthritis: a multiparameter prospective study. Ann Rheum Dis. 2004;63(6):675-680. doi:10.1136/ard.2003.010611.
Pincus T, Sokka T, Kavanaugh A. Relative versus absolute goals of therapies for RA: ACR 20 or ACR 50 responses versus target values for “near remission” of DAS or single measures. Clin Exp Rheumatol. 2004;22(5 Suppl 35):S50-S56.
Rezaei H, Saevarsdottir S, Forslind K, et al. In early rheumatoid arthritis, patients with a good initial response to methotrexate have excellent 2-year clinical outcomes, but radiological progression is not fully prevented: data from the methotrexate responders population in the SWEFOT trial. Ann Rheum Dis. 2012;71(2):186-191. doi:10.1136/annrheumdis-2011-200038.
Villaverde García V, Balsa Criado A. Does early treatment of Rheumatoid Arthritis lead to a better long-term prognosis? Reumatología Clínica (English Edition). 2010;6(2):106-110. doi:10.1016/S2173-5743(10)70024-1.
Fautrel B, Granger B, Combe B, Saraux A, Guillemin F, Le Loet X. Matrix to predict rapid radiographic progression of early rheumatoid arthritis patients from the community treated with methotrexate or leflunomide: results from the ESPOIR cohort. Arthritis Res Ther. 2012;14(6):R249. doi:10.1186/ar4092.
Forslind K, Hafström I, Ahlmén M. Sex: a major predictor of remission in early rheumatoid arthritis? Ann Rheum Dis. 2007;66(1):46-52. doi:10.1136/ard.2006.056937.
Demoruelle MK, Deane KD. Treatment strategies in early rheumatoid arthritis and prevention of rheumatoid arthritis. Curr Rheumatol Rep. 2012;14(5):472-480. doi:10.1007/s11926-012-0275-1.
Kyburz D, Gabay C, Michel BA, Finckh A, physicians of SCQM-RA. The long-term impact of early treatment of rheumatoid arthritis on radiographic progression: a population-based cohort study. Rheumatology (Oxford). 2011;50(6):1106-1110. doi:10.1093/rheumatology/keq424.
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