Enhanced treatment strategies and distinct disease outcomes among autoantibody-positive and -negative rheumatoid arthritis patients over 25 years: A longitudinal cohort study in the Netherlands
Autoři:
Xanthe M. E. Matthijssen aff001; Ellis Niemantsverdriet aff001; Tom W. J. Huizinga aff001; Annette H. M. van der Helmvan Mil aff001
Působiště autorů:
Department of Rheumatology, Leiden University Medical Center, Leiden, Netherlands
aff001
Vyšlo v časopise:
Enhanced treatment strategies and distinct disease outcomes among autoantibody-positive and -negative rheumatoid arthritis patients over 25 years: A longitudinal cohort study in the Netherlands. PLoS Med 17(9): e32767. doi:10.1371/journal.pmed.1003296
Kategorie:
Research Article
doi:
https://doi.org/10.1371/journal.pmed.1003296
Souhrn
Background
Based on different genetic and environmental risk factors and histology, it has been proposed that rheumatoid arthritis (RA) consists of 2 types: autoantibody-positive and autoantibody-negative RA. However, until now, this remained hypothetical. To assess this hypothesis, we studied whether the long-term outcomes differed for these 2 groups of RA patients.
Methods and findings
In the Leiden Early Arthritis Clinic cohort, 1,285 consecutive RA patients were included between 1993 and 2016 and followed yearly. Treatment protocols in routine care improved over time, irrespective of autoantibody status, and 5 inclusion periods were used as instrumental variables: 1993–1996, delayed mild disease-modifying antirheumatic drug (DMARD) initiation (reference period); 1997–2000, early mild DMARDs; 2001–2005, early methotrexate; 2006–2010, early methotrexate followed by treat-to-target adjustments; 2011–2016, similar to 2006–2010 plus additional efforts for very early referral. Three long-term outcomes were studied: sustained DMARD-free remission (SDFR) (persistent absence of clinical synovitis after DMARD cessation), mortality, and functional disability measured by yearly Health Assessment Questionnaire (HAQ). Treatment response in the short term (disease activity) was measured by Disease Activity Score–28 with erythrocyte sedimentation rate (DAS28-ESR). Linear mixed models and Cox regression were used, stratified for autoantibody positivity, defined as IgG anti-CCP2 and/or IgM rheumatoid factor positivity. In total, 823 patients had autoantibody-positive RA (mean age 55 years, 67% female); 462 patients had autoantibody-negative RA (age 60 years, 64% female). Age, gender, and percentage of autoantibody-positive patients were stable throughout the inclusion periods. Disease activity significantly decreased over time within both groups. SDFR rates increased after introduction of treat-to-target (hazard ratio [HR] 2006–2010 relative to 1993–1996: 3.35 [95% CI 1.46 to 7.72; p = 0.004]; HR 2011–2016: 4.57 [95% CI 1.80 to 11.6; p = 0.001]) in autoantibody-positive RA, but not in autoantibody-negative RA. In autoantibody-positive RA, mortality decreased significantly after the introduction of treat-to-target treatment adjustments (HR 2006–2010: 0.56 [95% CI 0.34 to 0.92; p = 0.023]; HR 2011–2016: 0.33 [95% CI 0.14 to 0.77; p = 0.010]), but not in autoantibody-negative RA (HR 2006–2010: 0.79 [95% CI 0.40 to 1.56; p = 0.50]; HR 2011–2016: 0.36 [95% CI 0.10 to 1.34; p = 0.13]). Similarly, functional disability improved in autoantibody-positive RA for the periods after 2000 relative to 1993–1996 (range −0.16 [95% CI −0.29 to −0.03; p = 0.043] to −0.32 [95% CI −0.44 to −0.20; p < 0.001] units of improvement), but not in autoantibody-negative RA (range 0.10 [95% CI −0.12 to 0.31; p = 0.38] to −0.13 [95% CI −0.34 to 0.07; p = 0.20] units of improvement). Limitations to note were that treatment was not randomized—but it was protocolized and instrumental variable analysis was used to obtain comparable groups—and that a limited spread of ethnicities was included.
Conclusions
Although disease activity has improved in both autoantibody-positive and autoantibody-negative RA in recent decades, the response in long-term outcomes differed. We propose that it is time to subdivide RA into autoantibody-positive RA (type 1) and autoantibody-negative RA (type 2), in the hope that this leads to stratified treatment in RA.
Klíčová slova:
Arthritis – Autoantibodies – Medical risk factors – Methotrexate – NSAIDs – Red blood cells – Rheumatoid arthritis – Sedimentation
Zdroje
1. Gale EAM. The discovery of type 1 diabetes. Diabetes. 2001;50(2):217. doi: 10.2337/diabetes.50.2.217 11272129
2. Padyukov L, Seielstad M, Ong RT, Ding B, Ronnelid J, Seddighzadeh M, et al. A genome-wide association study suggests contrasting associations in ACPA-positive versus ACPA-negative rheumatoid arthritis. Ann Rheum Dis. 2011;70(2):259–65. doi: 10.1136/ard.2009.126821 21156761
3. Deane KD, Demoruelle MK, Kelmenson LB, Kuhn KA, Norris JM, Holers VM. Genetic and environmental risk factors for rheumatoid arthritis. Best Pract Res Clin Rheumatol. 2017;31(1):3–18. doi: 10.1016/j.berh.2017.08.003 29221595
4. Pedersen M, Jacobsen S, Klarlund M, Pedersen BV, Wiik A, Wohlfahrt J, et al. Environmental risk factors differ between rheumatoid arthritis with and without auto-antibodies against cyclic citrullinated peptides. Arthritis Res Ther. 2006;8(4):R133. doi: 10.1186/ar2022 16872514
5. van der Helm-van Mil AH, Verpoort KN, Breedveld FC, Toes RE, Huizinga TW. Antibodies to citrullinated proteins and differences in clinical progression of rheumatoid arthritis. Arthritis Res Ther. 2005;7(5):R949–58. doi: 10.1186/ar1767 16207336
6. Cader MZ, Filer AD, Buckley CD, Raza K. The relationship between the presence of anti-cyclic citrullinated peptide antibodies and clinical phenotype in very early rheumatoid arthritis. BMC Musculoskelet Disord. 2010;11:187. doi: 10.1186/1471-2474-11-187 20731815
7. de Punder YM, Hendrikx J, den Broeder AA, Valls Pascual E, van Riel PL, Fransen J. Should we redefine treatment targets in rheumatoid arthritis? Low disease activity is sufficiently strict for patients who are anticitrullinated protein antibody-negative. J Rheumatol. 2013;40(8):1268–74. doi: 10.3899/jrheum.121438 23729803
8. van Oosterhout M, Bajema I, Levarht EWN, Toes REM, Huizinga TWJ, van Laar JM. Differences in synovial tissue infiltrates between anti-cyclic citrullinated peptide-positive rheumatoid arthritis and anti–cyclic citrullinated peptide-negative rheumatoid arthritis. Arthritis Rheum. 2008;58(1):53–60. doi: 10.1002/art.23148 18163491
9. Gomez-Puerta JA, Celis R, Hernandez MV, Ruiz-Esquide V, Ramirez J, Haro I, et al. Differences in synovial fluid cytokine levels but not in synovial tissue cell infiltrate between anti-citrullinated peptide/protein antibody-positive and -negative rheumatoid arthritis patients. Arthritis Res Ther. 2013;15(6):R182. doi: 10.1186/ar4372 24485167
10. van den Broek M, Dirven L, Klarenbeek NB, Molenaar TH, Han KH, Kerstens PJ, 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(2):245–8. doi: 10.1136/annrheumdis-2011-200379 22110122
11. Mustila A, Korpela M, Haapala AM, Kautiainen H, Laasonen L, Mottonen T, et al. Anti-citrullinated peptide antibodies and the progression of radiographic joint erosions in patients with early rheumatoid arthritis treated with FIN-RACo combination and single disease-modifying antirheumatic drug strategies. Clin Exp Rheumatol. 2011;29(3):500–5. 21640044
12. Seegobin SD, Ma MH, Dahanayake C, Cope AP, Scott DL, Lewis CM, et al. ACPA-positive and ACPA-negative rheumatoid arthritis differ in their requirements for combination DMARDs and corticosteroids: secondary analysis of a randomized controlled trial. Arthritis Res Ther. 2014;16(1):R13. doi: 10.1186/ar4439 24433430
13. Hafstrom I, Engvall IL, Ronnelid J, Boonen A, van der Heijde D, Svensson B. Rheumatoid factor and anti-CCP do not predict progressive joint damage in patients with early rheumatoid arthritis treated with prednisolone: a randomised study. BMJ Open. 2014;4(7):e005246. doi: 10.1136/bmjopen-2014-005246 25079933
14. de Rooy DP, van der Linden MP, Knevel R, Huizinga TW, van der Helm-van Mil AH. Predicting arthritis outcomes—what can be learned from the Leiden Early Arthritis Clinic? Rheumatology (Oxford). 2011;50(1):93–100. doi: 10.1093/rheumatology/keq230 20639266
15. Nederlands Huisartsen Genootschap. NHG-Standaard: Artritis. Utrecht: Nederlands Huisartsen Genootschap; 2017 [cited 2020 Mar 30]. Available from: https://www.nhg.org/standaarden/volledig/nhg-standaard-artritis.
16. Nordberg LB, Lillegraven S, Aga AB, Sexton J, Olsen IC, Lie E, et al. Comparing the disease course of patients with seronegative and seropositive rheumatoid arthritis fulfilling the 2010 ACR/EULAR classification criteria in a treat-to-target setting: 2-year data from the ARCTIC trial. RMD Open. 2018;4(2):e000752. doi: 10.1136/rmdopen-2018-000752 30564452
17. van der Helm-van Mil AH, Zink A. What is rheumatoid arthritis? Considering consequences of changed classification criteria. Ann Rheum Dis. 2017;76(2):315–7. doi: 10.1136/annrheumdis-2016-209629 27658679
18. Boeters DM, Burgers LE, Toes RE, van der Helm-van Mil A. Does immunological remission, defined as disappearance of autoantibodies, occur with current treatment strategies? A long-term follow-up study in rheumatoid arthritis patients who achieved sustained DMARD-free status. Ann Rheum Dis. 2019;78(11):1497–504. doi: 10.1136/annrheumdis-2018-214868 31413004
19. StatLine. [Persons moving between municipalities.] The Hague: Statistics Netherlands; 2017 [cited 2019 Mar 13]. Available from: https://statline.cbs.nl/Statweb/publication/?DM=SLNL&PA=81734NED&D1=0&D2=0,41&D3=0,41&D4=l&VW=T.
20. Ajeganova S, van Steenbergen HW, Verheul MK, Forslind K, Hafström I, Toes REM, et al. The association between anti-carbamylated protein (anti-CarP) antibodies and radiographic progression in early rheumatoid arthritis: a study exploring replication and the added value to ACPA and rheumatoid factor. Ann Rheum Dis. 2017;76(1):112–8. doi: 10.1136/annrheumdis-2015-208870 27117699
21. De Winter LM, Hansen WL, van Steenbergen HW, Geusens P, Lenaerts J, Somers K, et al. Autoantibodies to two novel peptides in seronegative and early rheumatoid arthritis. Rheumatology (Oxford). 2016;55(8):1431–6. doi: 10.1093/rheumatology/kew198 27094600
22. Mathsson L, Mullazehi M, Wick MC, Sjoberg O, van Vollenhoven R, Klareskog L, et al. Antibodies against citrullinated vimentin in rheumatoid arthritis: higher sensitivity and extended prognostic value concerning future radiographic progression as compared with antibodies against cyclic citrullinated peptides. Arthritis Rheum. 2008;58(1):36–45. doi: 10.1002/art.23188 18163519
23. Goldbach-Mansky R, Lee J, McCoy A, Hoxworth J, Yarboro C, Smolen JS, et al. Rheumatoid arthritis associated autoantibodies in patients with synovitis of recent onset. Arthritis Res. 2000;2(3):236–43. doi: 10.1186/ar93 11056669
24. van der Heide A, Jacobs JW, Bijlsma JW, Heurkens AH, van Booma-Frankfort C, van der Veen MJ, et al. The effectiveness of early treatment with “second-line” antirheumatic drugs. A randomized, controlled trial. Ann Intern Med. 1996;124(8):699–707. doi: 10.7326/0003-4819-124-8-199604150-00001 8633829
25. van Ede AE, Laan RF, Rood MJ, Huizinga TW, van de Laar MA, van Denderen CJ, et al. Effect of folic or folinic acid supplementation on the toxicity and efficacy of methotrexate in rheumatoid arthritis: a forty-eight week, multicenter, randomized, double-blind, placebo-controlled study. Arthritis Rheum. 2001;44(7):1515–24. doi: 10.1002/1529-0131(200107)44:7<1515::Aid-art273>3.0.Co;2–7 11465701
26. Goekoop-Ruiterman YP, de Vries-Bouwstra JK, Allaart CF, van Zeben D, Kerstens PJ, Hazes JM, 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):3381–90. doi: 10.1002/art.21405 16258899
27. van der Linden MP, le Cessie S, Raza K, van der Woude D, Knevel R, Huizinga TW, et al. Long-term impact of delay in assessment of patients with early arthritis. Arthritis Rheum. 2010;62(12):3537–46. doi: 10.1002/art.27692 20722031
28. van Nies JA, Brouwer E, van Gaalen FA, Allaart CF, Huizinga TW, Posthumus MD, et al. Improved early identification of arthritis: evaluating the efficacy of Early Arthritis Recognition Clinics. Ann Rheum Dis. 2013;72(8):1295–301. doi: 10.1136/annrheumdis-2012-202289 22952388
29. Sorensen J, Hetland ML. Diagnostic delay in patients with rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis: results from the Danish nationwide DANBIO registry. Ann Rheum Dis. 2015;74(3):e12. doi: 10.1136/annrheumdis-2013-204867 24534758
30. 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. doi: 10.1136/annrheumdis-2016-210715 28264816
31. Singh JA, Saag KG, Bridges SL Jr, Akl EA, Bannuru RR, Sullivan MC, et al. 2015 American College of Rheumatology guideline for the treatment of rheumatoid arthritis. Arthritis Care Res. 2016;68(1):1–25. doi: 10.1002/acr.22783 26545825
32. Maini R, St Clair EW, Breedveld F, Furst D, Kalden J, Weisman M, et al. Infliximab (chimeric anti-tumour necrosis factor alpha monoclonal antibody) versus placebo in rheumatoid arthritis patients receiving concomitant methotrexate: a randomised phase III trial. ATTRACT Study Group. Lancet. 1999;354(9194):1932–9. doi: 10.1016/s0140-6736(99)05246-0 10622295
33. Sengul I, Akcay-Yalbuzdag S, Ince B, Goksel-Karatepe A, Kaya T. Comparison of the DAS28-CRP and DAS28-ESR in patients with rheumatoid arthritis. Int J Rheum Dis. 2015;18(6):640–5. doi: 10.1111/1756-185x.12695 26013310
34. van der Woude D, Young A, Jayakumar K, Mertens BJ, Toes RE, van der Heijde D, et al. Prevalence of and predictive factors for sustained disease-modifying antirheumatic drug-free remission in rheumatoid arthritis: results from two large early arthritis cohorts. Arthritis Rheum. 2009;60(8):2262–71. doi: 10.1002/art.24661 19644846
35. Ajeganova S, van Steenbergen HW, van Nies JA, Burgers LE, Huizinga TW, van der Helm-van Mil AH. Disease-modifying antirheumatic drug-free sustained remission in rheumatoid arthritis: an increasingly achievable outcome with subsidence of disease symptoms. Ann Rheum Dis. 2016;75(5):867–73. doi: 10.1136/annrheumdis-2014-207080 25972519
36. van Tuyl LH, Sadlonova M, Hewlett S, Davis B, Flurey C, Goel N, et al. The patient perspective on absence of disease activity in rheumatoid arthritis: a survey to identify key domains of patient-perceived remission. Ann Rheum Dis. 2017;76(5):855–61. doi: 10.1136/annrheumdis-2016-209835 27903508
37. Bruce B, Fries JF. The Stanford Health Assessment Questionnaire: dimensions and practical applications. Health Qual Life Outcomes. 2003;1:20. doi: 10.1186/1477-7525-1-20 12831398
38. Kosinski M, Zhao SZ, Dedhiya S, Osterhaus JT, Ware JE Jr. Determining minimally important changes in generic and disease-specific health-related quality of life questionnaires in clinical trials of rheumatoid arthritis. Arthritis Rheum. 2000;43(7):1478–87. doi: 10.1002/1529-0131(200007)43:7<1478::Aid-anr10>3.0.Co;2-m 10902749
39. Poppelaars PB, van Tuyl LHD, Boers M. Normal mortality of the COBRA early rheumatoid arthritis trial cohort after 23 years of follow-up. Ann Rheum Dis. 2019;78:586–9. doi: 10.1136/annrheumdis-2018-214618 30808623
40. Matthijssen XM, Huizinga TW, Niemantsverdriet E, van der Helm-van Mil AH. Early intensive treatment normalises excess mortality in ACPA-negative RA but not in ACPA-positive RA. Ann Rheum Dis. 2019 Jun 22. doi: 10.1136/annrheumdis-2019-215843 31229951
41. Boer AC, Boonen A, van der Helm van Mil AHM. Is anti-citrullinated protein antibody-positive rheumatoid arthritis still a more severe disease than anti-citrullinated protein antibody-negative rheumatoid arthritis? A longitudinal cohort study in rheumatoid arthritis patients diagnosed from 2000 onward. Arthritis Care Res. 2018;70(7):987–96. doi: 10.1002/acr.23497 29266813
42. Versteeg GA, Steunebrink LMM, Vonkeman HE, Ten Klooster PM, van der Bijl AE, van de Laar M. Long-term disease and patient-reported outcomes of a continuous treat-to-target approach in patients with early rheumatoid arthritis in daily clinical practice. Clin Rheumatol. 2018;37(5):1189–97. doi: 10.1007/s10067-017-3962-5 29388086
43. Gwinnutt JM, Symmons DPM, MacGregor AJ, Chipping JR, Marshall T, Lunt M, et al. Have the 10-year outcomes of patients with early inflammatory arthritis improved in the new millennium compared with the decade before? Results from the Norfolk Arthritis Register. Ann Rheum Dis. 2018;77(6):848–54. doi: 10.1136/annrheumdis-2017-212426 29475855
44. van Gestel AM, Haagsma CJ, van Riel PLCM. Validation of rheumatoid arthritis improvement criteria that include simplified joint counts. Arthritis Rheum. 1998;41(10):1845–50. doi: 10.1002/1529-0131(199810)41:10<1845::Aid-art17>3.0.Co;2-k 9778226
45. Viatte S, Plant D, Raychaudhuri S. Genetics and epigenetics of rheumatoid arthritis. Nature Rev Rheumatol. 2013;9(3):141–53. doi: 10.1038/nrrheum.2012.237 23381558
46. Humby F, Lewis M, Ramamoorthi N, Hackney JA, Barnes MR, Bombardieri M, et al. Synovial cellular and molecular signatures stratify clinical response to csDMARD therapy and predict radiographic progression in early rheumatoid arthritis patients. Ann Rheum Dis. 2019;78(6):761–72. doi: 10.1136/annrheumdis-2018-214539 30878974
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