F. Raeman

Methotrexate in combination with other DMARDs is not superior to methotrexate alone for remission induction with moderate-to-high-dose glucocorticoid bridging in early rheumatoid arthritis after 16 weeks of treatment: the CareRA trial

Objectives To compare the efficacy and safety of intensive combination strategies with glucocorticoids (GCs) in the first 16 weeks (W) of early rheumatoid arthritis (eRA) treatment, focusing on high-risk patients, in the Care in early RA trial. Methods 400 disease-modifying antirheumatic drugs (DMARD)-naive patients with eRA were recruited and stratified into high risk or low risk according to classical prognostic markers. High-risk patients (n=290) were randomised to 1/3 treatment strategies: combination therapy for early rheumatoid arthritis (COBRA) Classic (methotrexate (MTX)+ sulfasalazine+60 mg prednisone tapered to 7.5 mg daily from W7), COBRA Slim (MTX+30 mg prednisone tapered to 5 mg from W6) and COBRA Avant-Garde (MTX+leflunomide+30 mg prednisone tapered to 5 mg from W6). Treatment modifications to target low-disease activity were mandatory from W8, if desirable and feasible according to the rheumatologist. The primary outcome was remission (28 joint disease activity score calculated with C-reactive protein <2.6) at W16 (intention-to-treat analysis). Secondary endpoints were good European League Against Rheumatism response, clinically meaningful health assessment questionnaire (HAQ) response and HAQ equal to zero. Adverse events (AEs) were registered. Results Data from 98 Classic, 98 Slim and 94 Avant-Garde patients were analysed. At W16, remission was reached in 70.4% Classic, 73.6% Slim and 68.1% Avant-Garde patients (p=0.713). Likewise, no significant differences were shown in other secondary endpoints. However, therapy-related AEs were reported in 61.2% of Classic, in 46.9% of Slim and in 69.1% of Avant-Garde patients (p=0.006). Conclusions For high-risk eRA, MTX associated with a moderate step-down dose of GCs was as effective in inducing remission at W16 as DMARD combination therapies with moderate or high step-down GC doses and it showed a more favourable short-term safety profile. EudraCT number: 2008-007225-39.

Effectiveness of methotrexate with step-down glucocorticoid remission induction (COBRA Slim) versus other intensive treatment strategies for early rheumatoid arthritis in a treat-to-target approach: 1-year results of CareRA, a randomised pragmatic open-label superiority trial

Objectives Combining disease-modifying antirheumatic drugs (DMARDs) with glucocorticoids (GCs) is an effective treatment strategy for early rheumatoid arthritis (ERA), yet the ideal schedule and feasibility in daily practice are debated. We evaluated different DMARD combinations and GC remission induction schemes in poor prognosis patients; and methotrexate (MTX) with or without GC remission induction in good prognosis patients, during the first treatment year. Methods The Care in ERA (CareRA) trial is a 2-year investigator-initiated randomised pragmatic open-label superiority trial comparing remission induction regimens in a treat-to-target approach. DMARD-inexperienced patients with ERA were stratified into a high-risk or low-risk group based upon presence of erosions, disease activity, rheumatoid factor and anticitrullinated protein antibodies. High-risk patients were randomised to a COBRA Classic (MTX + sulfasalazine + prednisone step-down from 60 mg), COBRA Slim (MTX + prednisone step-down from 30 mg) or COBRA Avant Garde (MTX + leflunomide + prednisone step-down from 30 mg) scheme. Low-risk patients were randomised to MTX tight step-up (MTX-TSU) or COBRA Slim. Primary outcome was the proportion of patients in 28 joint disease activity score calculated with C-reactive protein remission at week 52 in an intention-to-treat analysis. Secondary outcomes were safety and effectiveness (ClinicalTrial.gov identifier NCT01172639). Results 98 COBRA Classic, 98 COBRA Slim (high risk), 93 COBRA Avant Garde, 47 MTX-TSU and 43 COBRA Slim (low risk) patients were evaluated. Remission was achieved in 64.3% (63/98) COBRA Classic, 60.2% (59/98) COBRA Slim (high risk) and 62.4% (58/93) COBRA Avant Garde patients at W52 (p=0.840); and in 57.4% (27/47) MTX-TSU and 67.4% (29/43) COBRA Slim (low risk) patients (p=0.329). Less adverse events occurred per patient with COBRA Slim (high risk) compared with COBRA Classic or COBRA Avant Garde (p=0.038). Adverse events were similar in MTX-TSU and COBRA Slim (low risk) patients (p=0.871). At W52, 76.0% patients were on DMARD monotherapy, 5.2% used GCs and 7.5% biologicals. Conclusions MTX with a moderate-dose GC remission induction scheme (COBRA Slim) seems an effective, safe, low-cost and feasible initial treatment strategy for patients with ERA regardless of their prognostic profile, provided a treat-to-target approach is followed. Trial registration numbers EudraCT-number 2008-007225-39 and NCT01172639; Results.

OP0180 Remission Induction with Dmard Combinations and Glucocorticoids is not Superior to Remission Induction with MTX Monotherapy and Glucocorticoids: Week 52 Results of the High-Risk Group from the Carera Trial

Background To date, intensive DMARD combination therapy with glucocorticoids (GCs) is the most effective treatment approach for the management of early Rheumatoid Arthritis (eRA). The ideal content of the combination and the dose of GCs are however not yet known. Objectives To compare different intensive combination treatment strategies associated with GCs in eRA patients with a poor prognosis at week (W)52 in the CareRA trial. Methods CareRA is a two year prospective investigator-initiated multicenter RCT rooted in daily practice. DMARD naïve eRA patients were stratified into a high or low-risk group based on classical prognostic markers (presence of erosions, rheumatoid factor, anti-cyclic citrullinated protein and DAS28(CRP). High-risk patients (n=290) were randomized to 1 of 3 treatment strategies. 1) Cobra Classic (n=98): Methotrexate (MTX)+Sulphasalazine+60mg prednisone tapered weekly to 7.5mg daily from W7 2) Cobra Slim (n=98): MTX+30mg prednisone tapered to 5 mg daily from W6 3) Cobra Avant-Garde (n=94):MTX+Leflunomide +30mg prednisone tapered to 5 mg daily from W6 From W28, GCs were tapered in all patients and stopped at W34. A predefined treat to target approach was applied. From W40, we aimed for DMARD monotherapy. Efficacy measures were proportions of DAS28(CRP) remission, good EULAR response, clinically meaningful HAQ response, HAQ=0 (ITT analysis). Radiographic progression was measured via the Sharp Van der Heijde score. Adverse events related to therapy (AEs) were registered. Missing data were imputed by last observation carried forward. Results Remission rates were 64.3%, 60.2% and 62.8% in the Classic, Slim and Avant-Garde group respectively (p=0.837). Also no other efficacy outcomes did not differ between groups. 82% of X-ray images were available at baseline. Radiographic progression was minimal. SvH scores were 1.3±2.1, 1.3±2.5 and 1.0±1.4 at baseline and changed over 52 weeks 0.3±0.5, 0.4±1.1 and 0.3±0.6 in the Classic, Slim and Avant-Garde group respectively (p=0.581). The total numbers of AEs were 182 in 65 Classic patients, 125 in 64 Slim patients and 174 in 72 Avant-Garde patients (p=0.026). Serious AEs were reported in 3 Classic, 2 Slim and 3 Avant-Garde patients. Conclusions High rates of remission were achieved at week 52 with csDMARDs and GCs in all remission induction schemes. Cobra Slim showed comparable efficacy with less adverse events compared to DMARD combinations with moderate or high GC dosages. Disclosure of Interest None declared

THU0117 Low-Risk Patients Also Benefit from Remission Induction Treatment in Early Rheumatoid Arthritis: Week 52 Results from the Carera Trial

Background Early intensive treatment to target is recommended in severe early Rheumatoid Arthritis (eRA). However, data are lacking in patients presenting without markers of poor prognosis. Objectives To compare Methotrexate (MTX) with or without Glucocorticoid (GC) remission induction in a tight control setting over 52 weeks in low-risk patients with eRA. Methods CareRA is a two year prospective investigator-initiated multicenter RCT rooted in daily practice. DMARD naïve eRA patients were stratified into a high or low-risk group according to classical prognostic markers (presence of erosions, rheumatoid factor, anti-cyclic citrullinated protein and disease activity). In the low-risk arm, 43 patients were randomized to 15mg MTX monotherapy following a Tight Step Up (MTX-TSU) approach and 47 patients to a Cobra Slim schedule (MTX+30mg prednisone tapered to 5mg daily from W6). GCs were tapered from W28 and stopped at W34. A predefined treat to target approach was applied. Efficacy measures were proportions of DAS28(CRP) remission, good EULAR response, clinically meaningful HAQ response, HAQ=0 and Area Under the Curve (AUC) for DAS28(CRP) (ITT analysis). Radiographic progression was measured via the Sharp Van der Heijde (SvH) method. Adverse events related to therapy (AEs) were registered. No power was calculated in this explorative study. Missing data were imputed via last observation carried forward. Results Remission rates at week 52 were 57.4% and 67.4% in the MTX-TSU and Cobra Slim group respectively (p=0.329). MTX-TSU patients had a higher AUC for DAS28(CRP) than Cobra Slim patients over 52 weeks of treatment (p=0.017). No other efficacy scores differed between groups. 76% of X-ray images were available at baseline. Radiographic progression was minimal. SvH scores were 0.7±1.1 and 0.9±1.5 at baseline and changed over 52 weeks 0.2±0.3 and 0.3±0.4 in the MTX-TSU and Cobra Slim group respectively (p=0.184). The numbers of AEs were 48 in 27 MTX-TSU patients and 49 in 20 Cobra Slim patients (p=0.871). Two serious AEs (pulmonary infection and anemia) were registered in the Cobra Slim group. We observed numerically more treatment adaptations and IM/IA GC injections in MTX-TSU patients. Conclusions Both RA therapies achieved high remission rates in a tight control setting at week 52. However, remission induction with Cobra Slim resulted in a more rapid and sustained disease control. MTX with or without GC remission induction showed a comparable safety profile. Disclosure of Interest None declared

THU0137 Associated with A Glucocorticoid Bridging Scheme, Methotrexate is as Effective Alone as in Combination with Other DMARDS for Early Rheumatoid Arthritis, with Fewer Reported Side Effects: 16 Weeks Remission Induction Data from the Carera Trial

Background In line with the window of opportunity theory, intensive DMARD combination therapy with glucocorticoids (GCs) is probably the most effective treatment approach for early Rheumatoid Arthritis (eRA), but the ideal content of the combination and the dose of GCs is not yet known. Objectives To compare the efficacy and safety of intensive treatment strategies associated with GCs at week (W)16, focusing on high risk patients. Methods CareRA is a prospective two-year investigator-initiated multicenter RCT rooted in daily practice. In this trial, 400 DMARD naïve eRA patients were stratified into high or low risk according to classical prognostic markers such as the presence of erosions, RF/ACPA and disease activity. High risk patients were randomized to 1/3 treatment strategies: COBRA Classic (MTX+ Sulphasalazine + 60mg GCs tapered to 7.5mg daily from W7), COBRA Slim (MTX + 30mg GCs tapered to 5 mg from W6) and COBRA Avant-Garde (MTX + Leflunomide + 30mg GCs tapered to 5 mg from W6). Treatment modifications to target low disease activity were mandatory from W8 onwards, if desirable and feasible according to the rheumatologist. The primary outcome was remission (DAS28(CRP) <2.6) at W16 (ITT analysis). Secondary endpoints were good EULAR response, clinically meaningful HAQ response and HAQ=0. Area under the curve (AUC) for DAS28(CRP) and proportion of treatment adaptations and GC injections were calculated. Adverse events (AEs) were registered. Missing data were imputed by the maximum likelihood method. Results 290 patients were stratified as high risk: 98 Classic, 98 Slim and 94 Avant-Garde patients. Remission was achieved in 70.4% COBRA CLASSIC patients, 73.5% COBRA SLIM patients, 68.1% COBRA AVANT-GARDE patients (p=0.713) at W16. No significant differences between groups were shown in the proportion with a good EULAR response, clinically meaningful HAQ response and HAQ=0 (all p>0.05). The AUC for DAS28(CRP) in the 3 treatment arms was equal (p=0.521). No difference in treatment adaptions or GCs injections was found at W16.Until W16, therapy related AEs were reported in 61.2% of Classic, in 46.9% of Slim and in 69.1% of Avant-Garde patients (p=0.006). Conclusions At W16, MTX associated with a moderate step-down dose of GCs was as effective as DMARD combination therapies with moderate or even high step down GC doses in high-risk eRA. The short-term safety profile of MTX with GCs alone was more favorable. Disclosure of Interest : None declared DOI 10.1136/annrheumdis-2014-eular.2137

Association of Inflammatory Bowel Disease and Acute Anterior Uveitis, but Not Psoriasis, With Disease Duration in Patients With Axial Spondyloarthritis: Results From Two Belgian Nationwide Axial Spondyloarthritis Cohorts

To determine the link between extraarticular manifestations (EAMs) and baseline characteristics in patients with axial spondyloarthritis (SpA), and to define their potentially differential prognostic value in 2 large, independent Belgian axial SpA cohorts with distinct recruitment periods.

OP0263 First Results from “Be-Giant”: Baseline Characteristics of an Early Spondyloarthritis Cohort

Background The underlying idea for the development of the ASAS classification criteria for Spondyloarthritis (SpA) was to allow earlier recognition and diagnosis of patients with axial and/or peripheral SpA, given the known long delay between symptom onset and definitive diagnosis when modified New York (mNY) criteria for ankylosing spondylitis are used [1]. However, diagnosis at an early disease stage automatically leads to a more heterogeneous population, including patients with less severe disease manifestations. One of the major current challenges in the field of SpA is the study of the natural evolution of these early patients, including the identification of prognostic factors and biomarkers of disease activity. Methods The BelGian Inflammatory Arthritis and spoNdylitis cohorT (Be-Giant) is a multicentre, observational cohort that includes consecutive patients, diagnosed with SpA by their treating rheumatologist. Patients that fulfill the ASAS classification criteria, are prospectively followed every 6 months: this includes patient-reported outcomes, a standardized clinical examination (peripheral joints, entheses, axial metrology), laboratory variables and imaging. Patients already fulfilling the mNY criteria at baseline are excluded. Results We report the baseline characteristics of the first 122 newly diagnosed SpA patients (Table 1). In the non-radiographic axial SpA (nr-axSpA) patients, a high prevalence of HLA B27 as well as a positive MRI of the sacroiliac joints, as defined by the ASAS criteria was noted. Consistent with other early cohorts, we found a slightly higher prevalence of female patients. Considering extra-articular manifestations, psoriasis was more prevalent in peripheral SpA, whereas uveitis was more prevalent in nr-axSpA. Inflammatory bowel disease was similar in both groups. Nr-axSpA and peripheral SpA patients have a similar burden of disease as reported by BASDAI, BASFI, HAQ. SF36 was significantly higher in nr- axSpA (P=0.032). Table 1. Baseline characteristics of Be-Giant cohort Nr-axial SpA (n=79) Peripheral SpA (n=43) median [range] median [range] Age, years 32.53 [16.27–56.08] 42.39 [18.13–66.86] Symptom duration, years 2.41 [0–22.71] 0.22 [0.02–18.71] HLA-B27(+) (%) 72.2 48.80 Positive MRI SIJ (%) 84.3 21.1 Male (%) 44.30 62.80 CRP (mg/dl) 0.30 [0–15.60] 0.70 [0–20.20] ESR (mm/h) 7.00 [1.00–71.00] 18.00 [1.00–99.00] Conclusions Be-Giant is a new cohort in which patients that are diagnosed by rheumatologists as early SpA are prospectively followed. To our knowledge, this is a unique population, which will allow to study the natural evolution of patients classified according to the ASAS criteria. Baseline characteristics are completely in line with other early SpA cohorts. An indisputable asset is the high prevalence of classification through the imaging arm of the ASAS criteria in up to 85%. References Sieper J, Rudwaleit M, Baraliakos X, et al. The Assessment of SpondyloArthritis international Society (ASAS) handbook: a guide to assess spondyloarthritis. Ann Rheum Dis 2009;68(Suppl 2):ii1-ii44. Acknowledgements The Be-Giant cohort is funded by an unrestricted grant by AbbVie. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.4951

THU0079 The Association between Patient Reported Outcomes and Clinical Examination in Newly Diagnosed Spondyloarthritis Patients: Results from the Be-Giant Cohort

Background The Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) is a well-known surrogate for the patients perception of disease activity, and is frequently used as an inclusion criteria for clinical trials. The BelGian Inflammatory Arthritis and spoNdylitis cohorT (Be-Giant) is a new multicentre, observational cohort in which patients with non-radiographic-axial Spondyloarthritis (nr-axSpA) and peripheral SpA, classified according to the ASAS criteria, are prospectively followed every six months. Objectives To assess the association between patient reported outcomes and clinical examination. Methods Currently 123 newly diagnosed early SpA patients have been included. The present study describes the link between the three BASDAI questions covering physical discomfort of SpA patients and their relationship with the clinical examination as defined by swollen joint count (SJC) and modified Maastricht Ankylosing Spondylitis Enthesitis Score (MASES), including evaluation of the plantar fascia. These questions include the overall level of AS neck, back or hip pain (question 2 (Q2)); the overall level of pain/swelling in joints other than neck, back or hips (Q3) and the overall level of discomfort from any areas tender to touch/pressure (Q4). Concerning peripheral joint involvement, we defined the following groups: no swollen joints, oligoarticular (1-3 SJC) and polyarticular disease (>3 SJC). Concerning enthesitis-scores, we distinguished between involvement of the heel entheses and the more axial located entheses of the MASES. Results In our cohort we found that patients presenting with swollen joints scored significantly higher with regard to BASDAI Q3, than patients without swollen joints (P<0.0001). Patients with oligo- or polyarticular disease also showed significantly higher ASDAS values compared to patients without synovitis (respectively P=0.001 and P=0.015). There was no significant difference between oligo- and polyarticular joint disease concerning global BASDAI, ASDAS or the individual BASDAI Q3. BASDAI Q4 was not influenced by the presence of axial enthesitis; nor was the global BASDAI or ASDAS. However, presence of heel enthesitis did result in significant higher values for BASDAI Q4 (P<0.0001), global BASDAI (P=0.002), but not ASDAS. When evaluating BASDAI Q2 we found significantly higher values in the presence of axial enthesitis. Conclusions In our early SpA cohort we found an association between patient reported outcomes and clinical examination. We found that BASDAI question 3 regarding pain or swelling of the joints does capture the presence of synovitis, but could not differentiate between oligo- and polyarticular disease. BASDAI question 4 about tender points seems to signal heel enthesitis rather than axial enthesitis. Axial enthesitis, in its turn, seems to be reported as neck, back or hip pain (BASDAI question 2). In conclusion, the different components of the BASDAI are a good reflection of the clinical examination. To our knowledge this is the first study to validate the link between patient-reported outcomes and the evaluation of the physician. Acknowledgements The Be-Giant cohort is funded by an unrestricted grant by AbbVie. Disclosure of Interest : None declared DOI 10.1136/annrheumdis-2014-eular.4995