ObjectivesTo compare 1-year clinical efficacy of (1) initial triple disease-modifying antirheumatic drug therapy (iTDT) with initial methotrexate (MTX) monotherapy (iMM) and (2) different glucocorticoid (GC) bridging therapies: oral versus a single intramuscular injection in early rheumatoid arthritis.MethodsIn a single-blinded randomised clinical trial patients were randomised into three arms: (A) iTDT (methotrexate+sulfasalazine+hydroxychloroquine) with GCs intramuscularly; (B) iTDT with an oral GC tapering scheme and (C) MTX with oral GCs similar to B. Primary outcomes were (1) area under the curve (AUC) of Health Assessment Questionnaire (HAQ) and Disease Activity Score (DAS) and (2) the proportion of patients with radiographic progression.Results281 patients were randomly assigned to arms A (n=91), B (n=93) or C (n=97). The AUC DAS and HAQ were respectively −2.39 (95% CI −4.77 to −0.00) and −1.67 (95% CI −3.35 to 0.02) lower in patients receiving iTDT than in those receiving iMM. After 3 months, treatment failure occurred less often in the iTDT group, resulting in 40% fewer treatment intensifications. The difference in treatment intensifications between the arms required to maintain the predefined treatment goal remained over time. No differences were seen between the two GC bridging therapies. Respectively 21%, 24% and 23% of patients in arms A, B and C had radiographic progression after 1 year. Patients receiving iTDT had more adjustments of their medication owing to adverse events than those receiving iMM.ConclusionsTreatment goals are attained more quickly and maintained with fewer treatment intensifications with iTDT than with iMM. However, no difference in radiographic progression is seen. Both GC bridging therapies are equally effective and, therefore, both can be used.Trial registration numberISRCTN26791028.

Objective. To identify axial spondyloarthritis (SpA) in Dutch primary care patients with chronic low back pain (CLBP), and to design a simple referral model for general practitioners (GPs) that would identify patients at risk for axial SpA. Methods. Patients (ages 20 -45 years) with CLBP were identified from GP records. Assessments included inflammatory back pain questionnaires, medical interviews, physical examinations, HLA-B27, C-reactive protein level, conventional radiography, and magnetic resonance imaging. The outcome measure was axial SpA defined by the Assessment of SpondyloArthritis international Society (ASAS) criteria. Multivariable regression analysis with bootstrapping was used to develop the referral model. Results. A total of 364 patients (mean ؎ SD age 36.3 ؎ 6.8 years) was recruited with a median symptom duration of 9.0 years. Eighty-six patients (24%) fulfilled the ASAS criteria for axial SpA. Of all potential determinants, the ASAS inflammatory back pain questionnaire, good response to nonsteroidal antiinflammatory drugs, family history of SpA, and symptom duration were identified as most relevant for diagnosing axial SpA by multivariable regression analysis related to axial SpA. The shrunken regression coefficients were, respectively, 1.04, 0.83, 0.73, and 0.23. The combination of these 4 items proved a useful area under the receiver operating characteristic curve of 0.75 (SE 0.03). In a simplified score model, at the suggested cutoff value of 1.5, the sensitivity was 83% and specificity was 59%. Conclusion. This study shows that 1 of 4 primary care patients with CLBP was classified as having axial SpA. A preselection in primary care based on a combination of clinical items may be useful to facilitate the identification of patients at risk of axial SpA.

BackgroundVarious cytokines and inflammatory mediators are known to be involved in the pathogenesis of rheumatoid arthritis (RA). We hypothesized that polymorphisms in selected inflammatory response and tissue repair genes contribute to the susceptibility to and severity of RA.MethodsPolymorphisms in TNFA, IL1B, IL4, IL6, IL8, IL10, PAI1, NOS2a, C1INH, PARP, TLR2 and TLR4 were genotyped in 376 Caucasian RA patients and 463 healthy Caucasian controls using single base extension. Genotype distributions in patients were compared with those in controls. In addition, the association of polymorphisms with the need for anti-TNF-α treatment as a marker of RA severity was assessed.ResultsThe IL8 781 CC genotype was associated with early onset of disease. The TNFA -238 G/A polymorphism was differentially distributed between RA patients and controls, but only when not corrected for age and gender. None of the polymorphisms was associated with disease severity.ConclusionsWe here report an association between IL8 781 C/T polymorphism and age of onset of RA. Our findings indicate that there might be a role for variations in genes involved in the immune response and in tissue repair in RA pathogenesis. Nevertheless, additional larger genomic and functional studies are required to further define their role in RA.

After 11 years, initial COBRA combination therapy resulted in numerically lower mortality and similar prevalence of comorbidity compared with initial SSZ monotherapy. In addition, lower progression of joint damage suggests long-term disease modification.

Background Long term studies with treat-to-target therapy are essential to guide treatment strategies. Objectives To compare clinical and radiographic outcomes of 4 treatment strategies in early rheumatoid arthritis (RA) patients after 10 years. Methods The BeSt study enrolled 508 patients with early RA. Patients were randomized to: 1 sequential monotherapy, 2 step-up therapy, 3 initial combination with prednisone, 4 initial combination with infliximab. Treatment adjustments were based on 3-monthly disease activity score (DAS) measurements (DAS>2.4: next step; DAS≤2.4 for ≥6 months: taper to maintenance dose, next if DAS<1.6 for ≥6 months: stop last drug). Functional ability (Health Assessment Questionnaire, HAQ) over time was analyzed with a linear mixed model (LMM). Annual X-rays were scored ine one session by 2 blinded readers with the Sharp van der Heijde Score (SHS). SHS progression was categorized per year into “no” (<0.5), “little” (≥0.5 - ≤5) and “much” (>5) and analyzed over time with a generalized LMM. Results 10 year follow-up was completed by 313 patients (62%). Drop-out rates were lowest in arm 4. Mean age of completers was 61 years and 67% were female. Mean (SD) DAS was 1.6 (0.8) and mean (SD) HAQ was 0.6 (0.6). 82% had a DAS≤2.4, 53% had a DAS<1.6, 15% were in drug-free remission (DFR) with a mean (median) duration of 52 (58) months. After 10 years, 38% were still on the initial treatment step, others had changed medication at least once. Toxicity was similar in all arms. Table 1 shows outcomes per treatment arm. The initial functional improvement achieved during year 1 was maintained during 10 years. Over time HAQ was significantly lower in arm 4 than in arm 2 (0.52 vs 0.70, p=0.03, other differences non-significant). Ten year progression rates were low in all arms. Over time, patients in arm 3 less often developed progression compared to arm 1 (p=0.03, other comparisons non-significant). If progression was present, estimates were 8, 11, 8 and 5 SHS progression in 10 years in arm 1 to 4, respectively. At t=10 years Arm 1 Arm 2 Arm 3 Arm 4 p N=126 N=121 N=133 N=128 DAS, mean ± SD* 1.7±0.7 1.7±0.8 1.5±0.8 1.6±0.8 0.333 HAQ, mean ± SD* 0.6±0.6 0.7±0.6 0.5±0.5 0.5±0.6 0.121 DAS≤2.4, n (%)* 61 (85) 43 (71) 59 (84) 75 (84) 0.102 DAS<1.6, n (%)* 36 (50) 28 (46) 40 (57) 50 (56) 0.507 DFR, n (%)* 11 (14) 11 (15) 12 (15) 13 (13) 0.604 On initial treatment, n (%)* 21 (28) 13 (19) 33 (42) 52 (58) <0.001 Current infliximab use, n (%)* 14 (18) 8 (12) 9 (12) 23 (25) 0.075 Drop out, n (%) 50 (40) 54 (45) 55 (41) 36 (28) 0.041 Patients with SAE, n (%) 62 (49) 51 (42) 61 (46) 66 (52) 0.473 ΔSHS, median (IQR)* 2.0 (0.0–11.0) 2.5 (0.0–13.5) 3.0 (0.3–11.3) 1.5 (0.0–6.0) 0.390 ΔSHS >5, n (%)* 24 (38) 23 (42) 27 (42) 21 (27) 0.190 ΔSHS >10, n (%)* 16 (25) 16 (29) 18 (28) 12 (15) 0.196 *Completers analysis. Conclusions 10 year follow-up in the BeSt study shows the benefit of continued treat-to-target therapy, steering at low disease activity. After initial improvement...