title: Benefit of early treatment in inflammatory polyarthritis patients with anti-cyclic citrullinated peptide antibodies versus those without antibodies.
abstract: OBJECTIVE
  To compare the clinical utility of anti-cyclic citrullinated peptide (anti-CCP) antibodies and rheumatoid factor (RF) testing in predicting both functional outcome and response to treatment in early inflammatory polyarthritis (IP) patients.
  
  
  METHODS
  A total of 916 IP subjects from a primary care incidence registry (1990-1994) had anti-CCP antibody and RF status determined at baseline. Mean change in Health Assessment Questionnaire (HAQ) score between baseline and 5 years was compared by antibody status. The effect of treatment with disease-modifying antirheumatic drugs and/or steroids over 5 years, early (<6 months of symptom onset) versus late initiation, and duration of treatment were also compared by anti-CCP antibody status. The analysis was adjusted for treatment decisions and censoring over the followup, using marginal structural models.
  
  
  RESULTS
  Anti-CCP antibody-positive patients (n = 268) had more severe disease both at presentation and 5 years of followup, and this was independent of RF. On adjustment, anti-CCP antibody-negative patients treated early experienced a significant improvement in functional disability compared with anti-CCP antibody-negative patients who were never treated (-0.31; 95% confidence interval [95% CI] -0.53, -0.08), and experienced additional benefit for each additional month of early treatment. Anti-CCP antibody-positive patients treated early did not have a significant improvement in HAQ score compared with those not treated (-0.14; 95% CI -0.52, 0.24).
  
  
  CONCLUSIONS
  In this first observational study to examine the influence of anti-CCP antibody status on treatment response, anti-CCP antibody-positive IP patients showed less benefit from treatment, particularly early treatment, than anti-CCP antibody-negative patients. This provides support for the inclusion of anti-CCP antibodies as well as RF in the classification criteria for rheumatoid arthritis and for stratification by anti-CCP antibody status in clinical trials.
authors.affiliation: Arthritis Research UK Epidemiology Unit, University of Manchester, Manchester, UK.
authors.forename: Tracey M
authors.initials: TM
authors.lastname: Farragher
authors.forename: Mark
authors.initials: M
authors.lastname: Lunt
authors.forename: Darren
authors.initials: D
authors.lastname: Plant
authors.forename: Diane K
authors.initials: DK
authors.lastname: Bunn
authors.forename: Anne
authors.initials: A
authors.lastname: Barton
authors.forename: Deborah P M
authors.initials: DP
authors.lastname: Symmons
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D018501:Antirheumatic Agents / Q000627:therapeutic use; D001168:Arthritis / Q000097:blood / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000175:diagnosis / Q000628:therapy; D001323:Autoantibodies / Q000097:blood*; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D010456:Peptides, Cyclic / Q000276:immunology*; D011237:Predictive Value of Tests; D012042:Registries; D012217:Rheumatoid Factor / Q000097:blood*; D012720:Severity of Illness Index; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D018501:Antirheumatic Agents; D001323:Autoantibodies; D010456:Peptides, Cyclic; C487763:cyclic citrullinated peptide; D012217:Rheumatoid Factor
references.citation: Arthritis Res Ther. 2006;8(4):R128
references.pmid: 16859535
references.citation: Arthritis Rheum. 2005 Nov;52(11):3433-8
references.pmid: 16255021
references.citation: Stat Med. 1999 Mar 30;18(6):681-94
references.pmid: 10204197
references.citation: Clin Exp Rheumatol. 2005 Sep-Oct;23(5 Suppl 39):S69-76
references.pmid: 16273788
references.citation: Rheumatology (Oxford). 2006 Dec;45(12):1558-65
references.pmid: 16705046
references.citation: Arthritis Rheum. 2001 Jun;44(6):1248-53
references.pmid: 11407682
references.citation: Br J Rheumatol. 1986 May;25(2):206-9
references.pmid: 3708236
references.citation: Nat Clin Pract Rheumatol. 2005 Nov;1(1):2-3
references.pmid: 16932617
references.citation: Ann Rheum Dis. 2009 Jan;68(1):69-74
references.pmid: 18375541
references.citation: Ann Intern Med. 1997 Oct 15;127(8 Pt 2):757-63
references.pmid: 9382394
references.citation: Arthritis Res Ther. 2004;6(4):R303-8
references.pmid: 15225365
references.citation: Biometrics. 1992 Jun;48(2):479-95
references.pmid: 1637973
references.citation: Arthritis Res Ther. 2006;8(1):R3
references.pmid: 16356192
references.citation: Am J Epidemiol. 2006 Jun 15;163(12):1149-56
references.pmid: 16624967
references.citation: Epidemiology. 1992 Jul;3(4):319-36
references.pmid: 1637895
references.citation: Ann Rheum Dis. 2009 Jun;68(6):914-21
references.pmid: 18662933
references.citation: Rheumatol Int. 2005 Nov;26(1):58-62
references.pmid: 15726373
references.citation: Ann Rheum Dis. 2004 Sep;63(9):1085-9
references.pmid: 15308517
references.citation: Ann Rheum Dis. 2004 Sep;63(9):1090-5
references.pmid: 15308518
references.citation: J Rheumatol. 2008 Mar;35(3):425-8
references.pmid: 18322974
references.citation: Rheumatology (Oxford). 2007 Feb;46(2):342-9
references.pmid: 16899498
references.citation: Ann Rheum Dis. 2007 Jan;66(1):34-45
references.pmid: 16396980
references.citation: Epidemiology. 2003 Nov;14(6):680-6
references.pmid: 14569183
references.citation: Ann Rheum Dis. 2006 Jul;65(7):845-51
references.pmid: 16606649
references.citation: Rheumatology (Oxford). 2006 Apr;45(4):478-80
references.pmid: 16287917
references.citation: Arthritis Rheum. 2008 May;58(5):1293-8
references.pmid: 18438829
references.citation: Ann Rheum Dis. 2005 Feb;64(2):196-201
references.pmid: 15458956
references.citation: Ann Rheum Dis. 2005 Feb;64(2):299-302
references.pmid: 15166003
references.citation: Ann Intern Med. 2007 Jun 5;146(11):797-808
references.pmid: 17548411
references.citation: Arthritis Rheum. 1988 Mar;31(3):315-24
references.pmid: 3358796
references.citation: Ann Rheum Dis. 2008 Aug;67(8):1194-5
references.pmid: 18621971
references.citation: Ann Rheum Dis. 2004 Oct;63(10):1218-21
references.pmid: 15361374
references.citation: Arthritis Rheum. 2006 Jan;54(1):38-46
references.pmid: 16385494
references.citation: Arthritis Rheum. 2003 Jan;48(1):46-53
references.pmid: 12528102
references.citation: Med Care. 1992 Jun;30(6):473-83
references.pmid: 1593914
references.citation: Rheumatology (Oxford). 2007 May;46(5):725-6
references.pmid: 17215261
references.citation: Am J Epidemiol. 1995 Dec 15;142(12):1255-64
references.pmid: 7503045
references.citation: Arthritis Rheum. 2008 Feb;58(2):359-69
references.pmid: 18240242
references.citation: Epidemiology. 2000 Sep;11(5):550-60
references.pmid: 10955408
references.citation: Acta Radiol Diagn (Stockh). 1977 Jul;18(4):481-91
references.pmid: 920239
references.citation: J Rheumatol. 2005 Nov;32(11):2089-94
references.pmid: 16265684
references.citation: Clin Exp Rheumatol. 2003 Sep-Oct;21(5 Suppl 31):S15-9
references.pmid: 14969045
references.citation: Arthritis Rheum. 2007 Sep;56(9):2929-35
references.pmid: 17763407
references.citation: Arthritis Rheum. 2000 Aug;43(8):1831-5
references.pmid: 10943873
references.citation: Ann Rheum Dis. 2001 Oct;60(10):956-61
references.pmid: 11557653
references.citation: Arthritis Rheum. 2001 May;44(5):1033-42
references.pmid: 11352234
references.citation: J Rheumatol. 2006 Mar;33(3):497-500
references.pmid: 16511906
references.citation: Arthritis Res Ther. 2004;6(3):R264-72
references.pmid: 15142273
references.citation: Ann Rheum Dis. 2006 Apr;65(4):453-8
references.pmid: 16176994
references.citation: Arthritis Rheum. 1999 Jul;42(7):1339-46
references.pmid: 10403260
references.citation: Ann Rheum Dis. 2005 Dec;64(12):1744-9
references.pmid: 15843452
references.citation: Ann Rheum Dis. 2007 Mar;66(3):302-7
references.pmid: 17079248
references.citation: Lancet. 2002 Apr 6;359(9313):1173-7
references.pmid: 11955534
references.citation: Br J Rheumatol. 1994 Aug;33(8):735-9
references.pmid: 8055200
references.citation: Epidemiology. 2000 Sep;11(5):561-70
references.pmid: 10955409