Abstract
Objective
Rheumatoid arthritis (RA) is an inflammatory, autoimmune systemic disease. This study aimed to compare the demographic, clinical characteristics, treatment choices, and treatment responses of seronegative (SN) and seropositive (SP) RA patients who were receiving or newly started biological treatment.
Methods
The files and records of patients registered with Hacettepe University Biological Database with RA diagnosis who were planned to use biological disease-modifying antirheumatic drugs (b-DMARDs) between 2010-2024 were scanned. RA patients were divided into two groups as SPRA and SNRA. Demographic characteristics, disease duration, bDMARD use follow-up period, comorbidities, RA extra-articular findings, visual analog scale (VAS) global, VAS pain, VAS fatigue, Health Assessment Questionnaire-Disability index were recorded for RA patients included in the study.
Results
Two thousand five hundred and fifty-nine patients were included in the study. Median age of the patients was 55 years and 2034 of them were female. 75% of the patients were SPRA, 25% were SNRA. Although the DAS-28 score did not create a statistically significant difference when compared between the two groups, the rate of patients with low disease activity was higher in the seronegative group, while the rate of patients with moderate and high disease activity was higher in the SPRA group. When patients were evaluated according to the disease activity score (DAS-28) disease activity score after b-DMARD treatment, the proportion of patients who achieved remission or low disease activity was higher in the seronegative group. Among extra-articular findings, the frequency of interstitial lung disease and sicca symptoms were higher in the SPRA group.
Conclusion
SPRA and SNRA can be considered as two separate subtypes of RA with differences in clinical features, extra-articular involvement findings, disease activities, treatment choices and treatment responses.
Keywords: Rheumatoid arthritis, seropositive, seronegative, b-DMARD
References
Guidelines for the management of rheumatoid arthritis. American college of rheumatology ad hoc committee on clinical guidelines. Rheum. 2002;46:328-46.
Hochberg MC. Adult and juvenile rheumatoid arthritis: current epidemiologic concepts. Epidemiol Rev. 1981;3:27-44.
Buch M, Emery P. The etiology and pathogenesis of rheumatoid arthritis. Hosp Pharm 2002;9:5-10.
Weissmann G. Pathogenesis of rheumatoid arthritis. J Clin Rheumatol. 2004;10(3 Suppl):S26-31.
Semble EL. Rheumatoid arthritis: new approaches for its evaluation andmanagement. Arch Phys Med Rehabil .1995;76:190-201.
Gravallese EM, Firestein GS. Rheumatoid arthritis - common origins, divergent mechanisms. N Engl J Med. 2023;388:529-42.
Whiting PF, Smidt N, Sterne JA, et al. Systematic review: accuracy of anti-citrullinated peptide antibodies for diagnosing rheumatoid arthritis. Ann Intern Med. 2010;152:456-64.
Finckh A, Liang MH. Anti-cyclic citrullinated peptide antibodies in the diagnosis of rheumatoid arthritis; bayes cleaers the haze. Ann Intern Med. 2007;146:816-7.
Volkov M, van Schie KA, van der Woude D. Autoantibodies and B cells: the ABC of rheumatoid arthritis pathophysiology. Immunol Rev. 2020;294:148-63.
Sokolova MV, Schett G, Steffen U. Autoantibodies in rheumatoid arthritis: his- torical background and novel findings. Clin Rev Allergy Immunol. 2022;63:138-51.
Bugatti S, Manzo A, Montecucco C, Caporali R. The clinical value of autoantibodies in rheumatoid arthritis. Front Med (Lausanne). 2018;5:339.
Willemze A, Trouw LA, Toes RE, Huizinga TW. The influence of ACPA status and characteristics on the course of RA. Nat Rev Rheumatol. 2012;8:144-52.
Arnett FC, Edworthy SM, Bloch DA, et al. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum. 1988;31:315-24.
Aletaha D, Neogi T, Silman AJ, et al. 2010 rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Arthritis Rheum. 2010;62:2569-81.
Lin CMA, Cooles FAH, Isaacs JD. Precision medicine: the precision gap in rheumatic disease. Nat Rev Rheumatol. 2022;18:725-33.
Nikiphorou E, Buch MH, Hyrich KL. Biologics registers in RA: methodological aspects, current role and future applications. Nat Rev Rheumatol. 2017;13:503-10.
Aletaha D, Landewe R, Karonitsch T, et al. Reporting disease activity in clinical trials of patients with rheumatoid arthritis: EULAR/ACR collaborative recommendations. Arthritis Rheum. 2008;59:1371-7.
Miller MD, Ferris DG. Measurement of subjective phenomena in primary care research: the visual analogue scale. Fam Pract Res J. 1993;13:15-24.
Küçükdeveci AA, Sahin H, Ataman S, Griffiths B, Tennant A. Issues in cross-cultural validity: example from the adaptation, reliability, and validity testing of a Turkish version of the Stanford Health Assessment Questionnaire. Arthritis Rheum. 2004;51:14-9.
Matthijssen XME, Niemantsverdriet E, Huizinga TWJ, Van Der Helm-Van Mil AHM. Enhanced treatment strategies and distinct disease outcomes among autoanti- body-positive and -negative rheumatoid ar- thritis patients over 25 years: a longitudinal cohort study in the Netherlands. PLoS Med. 2020;17:e1003296.
Meyer O, Labarre C, Dougados M, et al. anticitrullinated protein/pep- tide antibody assays in early rheumatoid arthritis for predicting five year radiographic damage. Ann Rheum Dis. 2003;62:120-6.
Smolen JS, Landewe R, Breedveld FC, et al. EULAR recommen- dations for the management of rheumatoid arthritis with synthetic and biological disease-modifying anti- rheumatic drugs: 2013 update. Ann Rheum Dis. 2014;73:492-509.
Farragher TM, Lunt M, Plant D, Bunn DK, Barton A, Symmons DP. Benefit of early treatment in inflam- matory polyarthritis patients with anti-cyclic citrullinated peptide antibodies versus those without anti- bodies. Arthritis Care Res (Hoboken). 2010;62:664-75.
Katchamat W, Koolvisoot A, Aromdee E, Chiowchanwesawakit P, Muengchan C. Associations of rheu- matoid factor and anti-citrullinated peptide antibody with disease progression and treatment outcomes in patients with rheumatoid arthritis. Rheumatol Int. 2015;35:1693-9.
Kastbom A, Strandberg G, Lindroos A, Skogh T. Anti-CCP antibody test predicts the disease ourse dur- ing 3 years in early rheumatoid arthritis (the Swedish TIRA project). Ann Rheum Dis. 2004;63:1085-9.
Forslind K, Ahlmen M, Eberhardt K, Hafstrom I, Svensson B, BARFOT Study Group. Prediction of radio- logical outcome in early rheumatoid arthritis in clinical practice: role of antibodies to citrullinated peptides (anti-CCP). Ann Rheum Dis. 2004;63:1090-5.
D’Onofrio B, van der Helm-van Mil A, W J Huizinga T, van Mulligen E. Inducibility or predestination? Queries and concepts around drug-free remission in rheumatoid arthritis. Expert Rev Clin Immunol. 2023;19:217-25.
Wientjes MHM, den Broeder AA, Welsing PMJ, Verhoef LM, van den Bemt BJF. Prediction of response to anti-TNF treatment using laboratory biomarkers in patients with rheumatoid arthritis: a systematic review. RMD Open. 2022;8:e002570.
Hambardzumyan K, Hermanrud C, Marits P, et al. Association of female sex and positive rheumatoid factor with low serum infliximab and anti-drug antibodies, related to treatment failure in early rheumatoid arthritis: results from the SWEFOT trial population. Scand J Rheumatol. 2019;48:362-6.
Isaacs JD, Cohen SB, Emery P, et al. Effect of baseline rheumatoid factor and anticitrullinated peptide antibody serotype on rituximab clinical response: a meta-analysis. Ann Rheum Dis. 2013;72:329-36.
Norris-Grey C, Cambridge G, Moore S, Reddy V, Leandro M. Long-term persistence of rituximab in patients with rheumatoid arthritis: an evaluation of the UCL cohort from 1998 to 2020. Rheumatology (Oxford). 2022;61:591-6.
Shipa MRA, Di Cicco M, Balogh E, et al. Drug-survival profiling of second-line biologic therapy in rheumatoid arthritis: choice of another tumour necrosis factor inhibitor or a biologic of different mode of action? Mod Rheumatol. 2023;33:700-7.
Alten R, Mariette X, Flipo RM, et al. Retention of subcutaneous abatacept for the treatment of rheumatoid arthritis: real-world results from the ASCORE study: an international 2-year observational study. Clin Rheumatol. 2022;41:2361-73.
Bird P, Hall S, Nash P, et al. Treatment outcomes in patients with seropositive versus seronegative rheumatoid arthritis in phase III randomised clinical trials of tofacitinib. RMD Open. 2019;5:e000742.
Sugawara M, Fujieda Y, Noguchi A, et al. Prediction of the intolerance or non-responder to Janus kinase inhibitors in patients with rheumatoid arthritis: a preliminary retrospective study with integrative cluster analysis. Clin Exp Rheumatol. 2022;40:1674-80.
Jin Y, Liu J, Desai RJ, Kim SC. Real-world treatment effectiveness of disease-modifying antirheumatic drugs by serostatus among patients with rheumatoid arthritis. ACR Open Rheumatol. 2023;5:571-80.
De Stefano L, Bugatti S, Mazzucchelli I, et al. Synovial and serum B cell signature of autoantibody-negative rheumatoid arthritis vs autoantibody-positive rheumatoid arthritis and psoriatic arthritis. Rheumatology (Oxford). 2024;63:1322-31.
De Stefano L, D’Onofrio B, Gandolfo S, et al. Seronegative rheumatoid arthritis: one year in review 2023. Clin Exp Rheumatol. 2023;41:554-64.
Koslow M, Young JR, Yi ES, et al. Rheumatoid pulmonary nodules: clinical and imaging features compared with malignancy. Eur Radiol. 2019;29:1684-92.
Kamiya H, Panlaqui OM. Systematic review and meta-analysis of the risk of rheumatoid arthritis-associated interstitial lung disease related to anti-cyclic citrullinated peptide (CCP) antibody. BMJ Open. 2021;11:e040465.
Kaipiainen-Seppanen O, Kautiainen H. Declining trend in the incidence of rheumatoid factor-positive rheumatoid arthritis in Finland 1980-2000. J Rheumatol. 2006;33:2132-8.
Enzer I, Dunn G, Jacobsson L, Bennett PH, Knowler WC, Silman A. An epidemiologic study of trends in prevalence of rheumatoid factor seropositivity in Pima Indians: evidence of a decline due to both secular and birth-cohort influences. Arthritis Rheum. 2002;46:1729-34.
Myasoedova E, Davis J, Matteson EL, Crowson CS. Is the epidemiology of rheumatoid arthritis changing? Results from a population-based incidence study, 1985-2014. Ann Rheum Dis. 2020;79:440-4.
