Predictors of good response to conventional synthetic DMARDs in early seronegative rheumatoid arthritis: data from the ESPOIR cohort
Tóm tắt
Early seronegative rheumatoid arthritis (RA) is considered a specific entity, especially regarding diagnostic issues and prognosis. Little is known about its potentially different initial clinical presentation and outcome. We aimed to determine predictors of good response to conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) in seronegative RA patients with early inflammatory arthritis. Patients from the ESPOIR cohort with early inflammatory arthritis fulfilling the 2010 ACR/EULAR classification criteria for RA despite negativity for both rheumatoid factor and anti-CCP antibodies. The primary endpoint was a good or moderate EULAR response assessed after 1 year of follow-up, given at least 3 months of treatment with a csDMARD. Secondary objectives were to compare the early therapeutic response to methotrexate (MTX) and leflunomide (LEF) versus other csDMARDs (hydroxychloroquine, sulfasalazine) and to identify factors associated with functional disability (Health Assessment Questionnaire-Disability Index [HAQ-DI] > 0.5 at 1 year) and structural progression (van der Heijde-modified total Sharp score > 1 and > 5 points at 1 year). Logistic regression analysis was used to determine independent predictors of outcomes. One hundred seventy-two patients were analyzed. Overall, 98/172 (57%) patients received MTX during the first year of follow-up. A good or moderate EULAR response at 1 year was associated with early use of csDMARDs (i.e., within 3 months after the first joint swelling) on univariate and multivariable analysis (odds ratio = 2.41 [95% confidence interval 1.07–5.42], p = 0.03). Response rates were not affected by other classical prognostic factors (i.e., baseline DAS28). Presence of erosions at baseline was associated with Sharp score progression > 1 point and > 5 points (both p = 0.03) at 1 year. HAQ-DI ≥ 1 at inclusion and active smoking were significantly associated with HAQ-DI > 0.5 at 1 year. Our results suggest that delay in initiation of csDMARD more than baseline clinical, biological, or imaging features predominantly affects the outcome in early seronegative RA. These findings confirm that the usual therapeutic concepts in RA (early treatment, tight control, and treat-to-target) should be applied similarly to both seropositive and seronegative disease forms. ClinicalTrials.gov: NCT03666091. Registered September 11, 2018.
Tài liệu tham khảo
Guillemin F, Saraux A, Guggenbuhl P, Roux CH, Fardellone P, Le Bihan E, et al. Prevalence of rheumatoid arthritis in France: 2001. Ann Rheum Dis. 2005;64(10):1427–30.
Mouterde G, Lukas C, Goupille P, et al. Association of anticyclic citrullinated peptide antibodies and/or rheumatoid factor status and clinical presentation in early arthritis: results from the ESPOIR Cohort. J Rheumatol. 2014;41:1614–22.
Vallbracht I, Rieber J, Oppermann M, Forger F, Siebert U, Helmke K, et al. Diagnostic and clinical value of anti-cyclic citrullinated peptide antibodies compared with rheumatoid factor isotypes in rheumatoid arthritis. Ann Rheum Dis. 2004;63:1079–84.
Mewar D, Coote A, Moore DJ, Marinou I, Keyworth J, Dickson MC, et al. Independent associations of anti-cyclic citrullinated peptide antibodies and rheumatoid factor with radiographic severity of rheumatoid arthritis. Arthritis Res Ther. 2006;8:R128.
Kastbom A, Strandberg G, Lindroos A, et al. Anti-CCP antibody test predicts the disease course during 3 years in early rheumatoid arthritis (the Swedish TIRA project). Ann Rheum Dis. 2004;63:1085–9.
Nell VP, Machold KP, Stamm TA, et al. Autoantibody profiling as early diagnostic and prognostic tool for rheumatoid arthritis. Ann Rheum Dis. 2005;64:1731–6.
van den Broek M, Dirven L, Klarenbeek NB, et al. The association of treatment response and joint damage with ACPA-status in recent-onset RA: a subanalysis of the 8-year follow-up of the BeSt study. Ann Rheum Dis. 2012;71:245–8.
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;66:34–45.
Smolen JS, Landewe R, Breedveld FC, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biologic disease-modifying antirheumatic drugs. Ann Rheum Dis. 2010;69:964–75.
Zink A, Listing J, Nieworth M, et al. The national database of the German collaborative arthritis centres: II-treatment of patients with rheumatoid arthritis. Ann Rheum Dis. 2001;60:207–13.
Benefit of early treatment in inflammatory polyarthritis patients with anti-cyclic citrullinated peptide antibodies versus those without antibodies. Arthritis Care Res. Arthritis Care Res. 2010;62:664–75.
Barra L, Pope JE, Orav JE, et al. Prognosis of seronegative patients in a large prospective cohort of patients with early inflammatory arthritis. J Rheumatol. 2014:2361–9.
da Mota LM, Dos Santos Neto LL, de Carvalho JF, Pereira IA, Burlingame R, Ménard HA, et al. The presence of anti-citrullinated protein antibodies (ACPA) and rheumatoid factor on patients with rheumatoid arthritis (RA) does not interfere with the chance of clinical remission in a follow-up of 3 years. Rheumatol Int. 2012;12:3807–12.
Combe B, Benessiano J, Berenbaum F, et al. The ESPOIR cohort: a ten-year follow-up of early arthritis in France: methodology and baseline characteristics of the 813 included patients. Joint Bone Spine. 2007;5:440–5.
Aletaha D, Neogi T, Silman A, et al. Rheumatoid arthritis classification criteria: an America College of Rheumatology/European League Against Rheumatism collaborative iniiative. Ann Rheum Dis. 2010;69:1580–8.
Prevoo ML, van ‘t Hof MA, Kuper HH, van Leeuwen MA, van de Putte LB, van Riel PL. Modified disease activity scores that include twenty-eightjoint counts. Development and validation in a prospective longitudinal study of patients with rheumatoid arthritis. Arthritis Rheum. 1995;38:44–8.
Guillemin F, Braincon S, Pourel J. [Measurement of the functional capacity in rheumatoid polyarthritis: a French adaptation of the Health Assessment Questionnaire (HAQ)]. [Article in French]. Rev Rhum Mal Osteoartic. 1991;58:459–65.
van der Heijde DM, van Riel PL, Nuver-Zwart IH, Gribnau FW, vad de Putte LB. Effects of hydroxychloroquine and sulphasalazine on progression of joint damage in rheumatoid arthritis. Lancet. 1989;333:1036–1038.
Lukas C, Combe B, Ravaud P, Sibilia J, Landew R, van der Heijde D. Favorable effect of very early disease-modifying antirheumatic drug treatment on radiographic progression in early inflammatory arthritis: data from the Étude et Suivi des polyarthrites indifférenciées récentes (study and followup of early undifferentiated polyarthritis). Arthritis Rheum. 2011;63(7):1804–11.
Maska L, Anderson J, Michaud K. Measures of functional status and quality of life in rheumatoid arthritis: Health Assessment Questionnaire Disability Index (HAQ), Modified Health Assessment Questionnaire (MHAQ), Multidimensional Health Assessment Questionnaire (MDHAQ), Health Assessment Questionnaire II (HAQ-II), Improved Health Assessment Questionnaire (Improved HAQ), and Rheumatoid Arthritis Quality of Life (RAQoL). Arthritis Care Res. 2011;63(Suppl 11):S4–13.
Smolen JS, Landewé R, Bijlsma J, Burmester G, Chatzidionysiou K, Dougados M, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2016 update. Ann Rheum Dis. 2017;76(6):960–77.
Farragher TM, Lunt M, Plant D, Bunn DK, Barton A, Symmons DPM. Benefit of early treatment in inflammatory polyarthritis patients with anti-cyclic citrullinated peptide antibodies versus those without antibodies. Arthritis Care Res. 2010;62(5):664–75.
Kastbom A, Strandberg G, Lindroos A, Skogh T. Anti-CCP antibody test predicts the disease course during 3 years in early rheumatoid arthritis (the Swedish TIRA project). Ann Rheum Dis. 2004;63(9):1085–9.
Barra L, Pope JE, Orav JE, Boire G, Haraoui B, Hitchon C, et al. Prognosis of seronegative patients in a large prospective cohort of patients with early inflammatory arthritis. J Rheumatol. 2014;41(12):2361–9.
Ursum J, Bos WH, van Dillen N, Dijkmans BA, van Schaardenburg D. Levels of anti-citrullinated protein antibodies and IgM rheumatoid factor are not associated with outcome in early arthritis patients: a cohort study. Arthritis Res Ther. 2010;12(1):R8.
Boers M. Rheumatoid arthritis. Treatment of early disease. Rheum Dis Clin North Am. 2001;27(2):405–14 x.
Möttönen T, Hannonen P, Korpela M, Nissilä M, Kautiainen H, Ilonen J, et al. Delay to institution of therapy and induction of remission using single-drug or combination-disease-modifying antirheumatic drug therapy in early rheumatoid arthritis. Arthritis Rheum. 2002;46(4):894–8.
Verstappen SMM, Jacobs JWG, Bijlsma JWJ, Heurkens AHM, van Booma-Frankfort C, Borg EJT, et al. Five-year followup of rheumatoid arthritis patients after early treatment with disease-modifying antirheumatic drugs versus treatment according to the pyramid approach in the first year. Arthritis Rheum. 2003;48(7):1797–807.
Emery P. Evidence supporting the benefit of early intervention in rheumatoid arthritis. J Rheumatol Suppl. 2002;66:3–8.
Katchamart W, Koolvisoot A, Aromdee E, Chiowchanwesawakit P, Muengchan C. Associations of rheumatoid factor and anti-citrullinated peptide antibody with disease progression and treatment outcomes in patients with rheumatoid arthritis. Rheumatol Int. 2015;35(10):1693–9.
Truchetet M-E, Dublanc S, Barnetche T, Vittecoq O, Mariette X, Richez C, et al. Association of the presence of anti-carbamylated protein antibodies in early arthritis with a poorer clinical and radiologic outcome: data from the French ESPOIR Cohort. Arthritis Rheumatol Hoboken NJ. 2017;69(12):2292–302.
Santos-Moreno P, Sánchez G, Castro C. Rheumatoid factor as predictor of response to treatment with anti-TNF alpha drugs in patients with rheumatoid arthritis: Results of a cohort study. Medicine (Baltimore). 2019;98(5):e14181.
Dixey J, Solymossy C, Young A, Early RA. Study. Is it possible to predict radiological damage in early rheumatoid arthritis (RA)? A report on the occurrence, progression, and prognostic factors of radiological erosions over the first 3 years in 866 patients from the Early RA Study (ERAS). J Rheumatol Suppl. 2004;69:48–54.