Extended report A TICORA26 Intensive 1 month Routine Intensive Routine 1 month C Fransen28 ‘Opinion oftreating rheumatologist’ 3 months (≠) B CAMERA27 Response Criteria* Intensive 1 month Routine 1 month Routine Intensive I Intensive II 1 month 1 month E Edmonds31 SJC +‘opinion of treating rheumatologist’ 3 months (≠) DAS28<3.2 LDA 2 months 3 months ‘Opinion of treating rheumatologist’ 2 months 3 months (=) At least every4 months 4 months(≠) CRP normal range SJC<3 IDntensivSeymmons29 (C+RSPJCb,esylomwptotwmicse)* upper limit of normal DMARDspianrcel.nCteycralolsspteorroinid,sC(yimcl,oipvh)osphamide, symptomcontrol NSAIDs, DMARDs, steroids(≠) DAS<2.4 LDA DMARD step up to trippletherapy; SPZ, MTX, HCQ,steroids, LEF, sod. aurothiomalat if active synovitis, or„LOE“ortoxicity, DMARD switch of monotherapy, stepup; steroids (≠) MTX dose adjustments s.c. application, add of cyclosporine MTX doseadjustments, s.c. application add of cyclosporine(=) DMARDs DMARDs (=) 18 months 2 years 24 weeks 3 years 2 years van Tuyl30 DAS28<3.2 LDA F Intensive I Intensive II G Stenger32 Experimental high risk Control high risk Experimental low risk 8 weeksCartilage degradation 13(≠w)eeks 8 weeks 13 weeks(=) CRP d?ecrease 50%* 8 weeksafter MTX, SPZ, AZA 6 months after i.m. gold ‘Opinion of treating rheumatologist’ week 8: DMARDs (COBRA treatment including MTX, SPZ, HCQ prednisolone), week21: add IFX 40 weeks week8: DMARDs, week21: IFX (=) DMARDs, stepup*, aggressive 2 years NSAIDs only, DMARD monotherapy(≠) 11.4% NSAIDs only, DMARD monother. (≠) Trial (A) TICORA study; Grigor et al, 200425 Groups Targeted Routine (B) CAMERA Targeted study; Verstappen et al, 200727 Routine Intensive Routine (C) Fransen et al, 200528 (D) Symmons Targeted et al, 200529 Routine (E) Edmonds Targeted I et al, (2a0b0s7t3r1act) Targeted II (F) van Tuyl Targeted I et al, 200830 Targeted II (G) Stenger Targeted et al, 199832 Routine Target DAS<2.4 LDA ‘Opinion of treating rheumatologist’ ; synovitis, ‘lack of efficacy’ Response criteria: >20% improvement compared to previous visit of SJC and 2 out of 3: ESR, TJC, PGA ≤50% improvement compared to baseline of SJC and 2 out of 3: ESR, TJC, PGA (inadequate response) SJC + ‘opinion of treating rheumatologist’ DAS28≤3.2 LDA ‘opinion of treating rheumatologist’ suppressing clinical and laboratory evidence of joint inflammati on: SJC & TJC = 0, CRP less than twice the upper limit of the normal range. ‘symptom control’ CRP normal range SJC<3 DAS28≤3.2 LDA Cartilage degradation (CTX-II≤150in ELISA) CRP decrease≤50% ‘opinion of treating rheumatologist’ Figure 2 Design of the seven core clinical trials. (A) TICORA study (Grigor et al 2004)26; (B) CAMERA study (Verstappen et al 2007)27; (C) Fransen et al 200528; (D) Symmons et al 200529; (E) Edmonds et al 2007 (abstract)31; (F) van Tuyl et al 200830; and (G) Stenger et al 1998.32 Intensive and routine treatment arms are displayed, red arrows mark the scheduled intervals for target assessment. Table 1 speciﬁes the targets of trials A–G. AZA, Azathioprine; CAMERA, Computer Assisted Management in Early Rheumatoid Arthritis; CRP, C reactive protein; DAS, Disease Activity Score; DMARD, disease-modifying antirheumatic drug; HCQ, hydroxychloroquine; IFX, ifosfamide; LDA, low disease activity; LEF, leﬂunomide; MTX, methotrexate; NSAID, non-steroidal anti-inﬂammatory drug; sc, subcutaneous; SJC, swollen joint count; sod., sodium; SPZ, sulﬁnpyrazone; TICORA, tight control of rheumatoid arthritis. Fransen et al28 showed that both the proportion of patients reaching LDA and frequency of DMARD changes during fol- low-up favoured a DAS28-driven DMARD strategy. Symmons et al29 found signiﬁcant differences in clinical outcomes in the evaluator global assessment, while other measures, including joint counts, erythrocyte sedimentation rate and patient global visual analogue scale, were not signiﬁcantly different. Physical function was the primary outcome in the trial by Symmons et al29; the intensive group failed to show signiﬁcant differences compared to routine care regarding HAQ changes. Also CAMERA27 did not show signiﬁcant differences in func- tional outcomes. Grigor et al26 reported signiﬁcantly less progression of radio- graphic changes26 in the intensive treatment group. In contrast, no signiﬁcant differences in annual radiographic progression were described in the CAMERA study.27 Two of the studies did not report radiographic data28 29 (table 1, ﬁgure 2). Randomised strategic trials comparing two targeted strategies van Tuyl et al30 presented a study protocol randomising early RA patients to different targeted and tight monitoring schedules: one 640 03_ar123976.indd 640 group aiming at DAS28 remission, the other at suppressing car- tilage degradation as assessed by measuring urinary C-terminal cross-linking of type II collagen. Results did not differ signiﬁ- cantly between the two groups with similar overall remission rates in both arms (ﬁgure 2, table 1). However, as the authors concede, this was a very small pilot study. Similarly, Edmonds et al31 reported in abstract form on steering at normal CRP levels versus a joint count targeted approach. Their results suggested that targeting CRP provides better interference with radio- graphic damage (table 1, ﬁgure 2). Non-randomised cohort studies comparing two targeted strategies Stenger et al32 compared an aggressive treatment protocol that stipulated change of DMARD therapy if after 8 weeks CRP decrease was less than 50% in patients with a high risk of developing aggressive disease; the comparator arm on reg- ular therapy was a retrospectively assessed group of high risk patients. After 2 years, the area under the curve for CRP was signiﬁcantly lower in the intensive treatment group than in the historic control. While no functional data were provided, Ann Rheum Dis 2010;69:638–643. doi:10.1136/ard.2009.123976 3/10/2010 11:52:41 AM