B. Vander Cruyssen

Anti-citrullinated peptide antibodies may occur in patients with psoriatic arthritis

Background: Anti-cyclic citrullinated peptide (anti-CCP) antibodies are considered highly specific markers of rheumatoid arthritis. Despite the high specificity of the test, anti-CCP antibodies have also been observed in psoriatic arthritis. Objective: To determine the frequency of anti-CCP antibodies in psoriatic arthritis and to describe the clinical characteristics of such patients. Methods: Serum samples from 192 patients with psoriatic arthritis were analysed for anti-CCP antibodies. A previously defined cut off point was applied at a specificity level of ⩾98.5% (42 U/ml). Antibodies against pepA and pepB (two synthetic citrullinated peptides) were determined on samples containing anti-CCP antibodies by line immune assay. The swollen joint count and the numbers of affected joints (present or past) were recorded. Clinical features were noted and if available radiographs of hands and feet were scored for erosions. Rheumatoid factor was determined in all samples. Results: Anti-CCP antibodies were found in 15 patients (7.8%); 13 of 15 anti-CCP2 positive samples were also positive for anti-pepA or pepB antibodies. The prevalence of anti-CCP antibodies was higher than expected in view of the highly specific cut off applied in the test. Detailed analysis of the clinical and radiological features makes it improbable that the high prevalence of anti-CCP antibodies resulted solely from concomitant psoriasis and rheumatoid arthritis or from misclassification. Conclusions: Anti-CCP antibodies may be present in patients with psoriatic arthritis. Although some of the present cohort could have had psoriasis with concomitant rheumatoid arthritis, a proportion at least had the typical characteristics of psoriatic arthritis as the primary diagnosis.

Fast and sharp decrease in calprotectin predicts remission by infliximab in anti-TNF naïve patients with ulcerative colitis.

AIM To evaluate the effect of infliximab induction therapy on calprotectin levels in patients with ulcerative colitis (UC). PATIENTS AND METHODS In this prospective study 53 patients with active UC from 17 centers were treated with infliximab therapy (5 mg/kg) at baseline, week 2, and week 6. Faecal calprotectin was measured every week. Sigmoidoscopies were performed at baseline, week 6 and week 10. RESULTS Median calprotectin levels decreased from 1260 (IQR 278.5- 3418) at baseline to 72.5 (IQR 18.5 - 463) at week 10 (p<0.001). After 10 weeks, infliximab therapy induced endoscopic remission and a decrease in calprotectin to<50 mg/kg or at least a 80% decrease from baseline level in 58% of patients. A significant and steep decrease of calprotectin levels was seen at week 2 for patients with an endoscopic remission at week 10 as compared to patients who did not show a remission. (p<0.001). At week 10 an excellent correlation was found between endoscopic remission and clinical Mayo score reflected by an AUC of ROC analyses of 0.94 (0.87-1) and with calprotectin measurements (AUC 0.91 (0.81-1)) : all patients with calprotectin levels <50 mg/kg, and a normal clinical Mayo score (=0) were in endoscopic remission. CONCLUSIONS Infliximab induces a fast and significant decrease of faecal calprotectin levels in anti-TNF naïve patients with ulcerative colitis predictive for remission of disease.

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.

CARD15 polymorphisms are associated with anti-Saccharomyces cerevisiae antibodies in caucasian Crohn's disease patients

Carriage of CARD15 gene polymorphisms and the serological marker anti‐Saccharomyces cerevisiae antibodies (ASCA) are two markers for Crohns disease (CD). Similar phenotypes have been associated with both markers. In the present study we analysed whether both markers were associated with each other and, if so, whether this association could be explained by a direct link or by an indirect association with those phenotypes. Therefore, we included 156 consecutive Caucasian CD patients and assessed the prevalence of the three common single nucleotide polymorphisms in the CARD15 gene. Serum samples were analysed for IgA and IgG ASCA by ELISA. CD patients with CARD15 polymorphisms were more frequently ASCA positive (OR 2·7 (1.4–5.2); P = 0·002) and had higher titres for ASCA IgA (P = 0·005) and ASCA IgG (P < 0·001) compared to patients carrying the wild type polymorphisms. Multivariate analysis demonstrated that this association was independent from ileal disease, penetrating disease and stricturing disease, the need for resective bowel surgery, familial cases, smoking habits and early age at onset. Homozygotes or compound heterozygotes for CARD15 polymorphisms had significantly more frequent ASCA positivity compared to single heterozygotes (OR 9·1 (1.1–74.2), Pc (corrected P‐value) = 0·030). These data indicate that there is a significant association between the carriage of CARD15 polymorphisms and ASCA, independent of the described phenotypes. Moreover, ASCA positivity is more frequent in CD patients carrying 2 CARD15 polymorphisms compared to single heterozygotes.

Reversible changes in serum immunoglobulin galactosylation during the immune response and treatment of inflammatory autoimmune arthritis

Objectives: Improved DNA sequencer-aided fluorophore-assisted carbohydrate electrophoresis (DSA-FACE) technology was used to monitor the changes in the galactosylation status of serum immunoglobulins during the immune response and therapy of autoimmune arthritis. Methods: Collagen-induced arthritis (CIA) was induced in susceptible DBA/1 mice and the undergalactosylation status (UGS) of serum immunoglobulins was determined using the improved DSA-FACE technology. Prophylactic intravenous tolerisation with type II collagen as well as semitherapeutic treatment with dexamethasone (DEX) were performed and UGS was analysed. Next, the serum immunoglobulin glycosylation profiles of patients with rheumatoid arthritis (RA) and spondyloarthropathy (SpA) were studied and changes in the UGS scores during anti-tumour necrosis factor (TNF)α therapy followed. Results: In the longitudinal CIA study, the undergalactosylation state of immunoglobulins was found to be significantly correlated with the clinical arthritis scores. Upon collagen-specific tolerisation as well as glucocorticoid semitherapeutic treatment, improvement of the clinical arthritis scores correlated with decreased levels of UGS. It was also demonstrated that withdrawal of DEX was associated with an increased UGS score. Interestingly, reversibility in the UGS was also shown during treatment of patients with RA and SpA with anti-TNFα. Conclusions: These findings demonstrate that the UGS of serum immunoglobulins changes during the disease course of CIA and that this UGS is inhibited by antigen-specific and antigen-independent treatment procedures. The observation that Ig galactosylation is a reversible process is also documented during treatment of patients with RA and SpA with anti-TNFα.

Do all anti-citrullinated protein/peptide antibody tests measure the same? Evaluation of discrepancy between anti-citrullinated protein/peptide antibody tests in patients with and without rheumatoid arthritis

Background: Different methods exist to demonstrate anti-citrullinated protein/peptide antibodies (ACPA). Aims: To evaluate discrepancy between four ACPA tests. Patients and methods: Population 1 consisted of patients with a new diagnostic problem, including 86 patients with rheumatoid arthritis (RA) and 450 patients without RA. Population 2 consisted of 155 patients with RA who had long-standing disease. Population 3 consisted of 188 patients with psoriatic arthritis and in population 4 there were 192 patients with systemic lupus erythematosus. Populations 1 and 2 were tested with the anti-human fibrinogen antibody (AhfibA) test, anti-CCP2 from Eurodiagnostica (CCP2-euro), anti-CCP2 from Pharmacia (CCP2-phar) and anti-CCP3 test by Inova (CCP3). Samples were annotated as discrepant if positive in one and negative in at least one other test. Each discrepant sample was re-analysed in a different run. Populations 3 and 4 were analysed in the CCP2-euro and AhFibA test. Results: In population 1, ACPA positivity was found in 17 of 450 (3.8%) patients without RA; 14 (82%) of these 17 samples were discrepant. In contrast, 61 of 86 (70.9%) patients with RA were ACPA positive of whom 18 of 61 (29.5%) were discrepant (70.9% vs. 29.5%, p<0.001). The discrepancies between tests could be partly attributed to borderline results, inter-assay discrepancy and inter-test variability. They were more prevalent in patients with systemic lupus erythematosus who were ACPA positive than in those with psoriatic arthritis who were ACPA positive. Conclusions: Discrepancy between different ACPA tests was observed attributable to the occurrence of borderline results, inter-assay variability and mainly to inter-test variability. The lowest inter-test discrepancy is observed between tests that use the same substrate.

Over-representation of construction-related occupations in male patients with systemic sclerosis

Aims: Based on preliminary observations, we tested the hypothesis that construction-related occupations are associated with systemic sclerosis (SSc). Methods: The professional occupation of 91 patients with SSc (71 females and 20 males) was recorded. Categorisation into construction-related and other professions was performed. A double definition was used for construction-related occupations. The first (limited) definition was based upon categories of the Belgian National Institute of Statistics (NIS) occupational list. The following occupations were considered construction-related: electricians, joiners, masons and tilers, plumbers and pipefitters. The use of this list also allows us to compare the distribution of professions in these patients with that in the general population. As the NIS occupational list is limitative and leaves out some “real-life” construction-related occupations, a second and broader interpretation was given to the concept of construction-related occupations. Results: The prevalence of construction-related professions in males with SSc, according to the limited definition, was 10-fold higher than in the general working population (50% vs 5%; p<0.001). Interestingly, most of the patients with construction-related occupations were electricians. In the broader interpretation, 75% of the men with SSc fell into the category of construction-related occupations. Conclusions: The data show an association between SSc and professional occupation.

OP0095 Randomized, Placebo-Controlled Trial To Evaluate Clinical Efficacy and Structure Modifying Properties of Subcutaneous Etanercept (ETN) in Patients with Erosive Inflammatory Hand Osteoarthritis (OA)

Background Erosive OA involves interphalangeal joints (IPJs), resulting in a high disease burden, for which treatment options are limited. Although it is characterized by joint inflammation, earlier treatment with TNF blockers was equivocal. Objectives To investigate the 1-year efficacy of ETN in erosive OA. Methods In a European multicentre study (NTR 1192) patients were equally randomized to subcutaneous ETN (24 weeks 50 mg weekly, thereafter 25 mg weekly) or placebo. Patients with erosive (≥1 IPJ with radiographic pre(erosive) anatomical phase (“J”/“E”) according to Verbruggen-Veys system) inflammatory (≥1 IPJ with soft swelling/erythema and with positive power Doppler at US) symptomatic (VAS pain >30/100 on NSAID use, flare after NSAID washout) OA were included. VAS pain, hand function (FIHOA), quality of life (SF-36), no. of tender joints and grip strength were assessed after 4, 8, 12, 24, 36 weeks and 1 year. Radiographic progression of IPJs was scored blindly in paired order (baseline, 24 weeks and 1 year) following the quantitative Ghent University Scoring System (GUSS, 0–300 per IPJ). With linear mixed models VAS pain was compared between treatment groups at 24 weeks (primary outcome), and 1 year in intention-to-treat (ITT) analyses. With general estimated equations secondary outcomes were analysed. Adjustments were made for centre, baseline values and patient effects were appropriate. Completers fulfilling the extensive inclusion criteria were included in per-protocol (PP) analyses. Results Of 284 screened patients, 90 (mean age 60 years, 81% women, 96% fulfilled ACR hand OA criteria) were randomized; 22 discontinued the study prematurely. At baseline patient characteristics did not differ between the groups. VAS pain in all patients decreased -24.8 mm (95%CI -29.2;-20.5 (P<0.001)) at 24 weeks. In ITT differences in pain between the groups were in favour of ETN, but did not reach statistical significance. However, in PP the difference reached statistical significance (table). No differences were seen on secondary clinical outcomes. The PP analysis of GUSS showed a mean difference in favour of ETN (table), indicating more remodelling in the ETN group. Additional analyses showed an interaction between soft swelling/erythema and ETN treatment on GUSS, resulting in a statistical significant (P<0.05) mean difference between ETN and placebo groups. More patients dropped out on placebo than on ETN (6 vs. 3) due to inefficacy, whereas more on ETN than on placebo (6 vs. 1) due to adverse effects. Conclusions In erosive OA ETN was not superior over placebo on VAS pain at 24 weeks. However in the symptomatic and inflammatory patients completing the study ETN was superior over placebo both on pain and structural damage assessed by GUSS; ETN was especially effective in joints with signs of inflammation. Acknowledgement Pfizer for supply of study medication and research grant. Disclosure of Interest None declared

Cyclodextrin polysulphate protects articular cartilage in experimental lapine knee osteoarthritis

OBJECTIVE To evaluate the in vivo chondroprotective effect of cyclodextrin polysulphate (CDPS) in a rabbit model of experimental osteoarthritis (OA). DESIGN Experimental OA was induced in rabbits by anterior cruciate ligament transection (ACLT). Forty-eight hours post-surgery, the rabbits were randomised into three treatment groups (n=15 in each group) and a sham-operated control group. The rabbits were either injected subcutaneously with saline, 0.25 mg/kg CDPS or 1 mg/kg CDPS once a week for a period of 12 weeks, and their weight was monitored as a parameter for their general status. The animals were then sacrificed for macroscopic and histological assessment of the knee joints. RESULTS At the lowest dose, CDPS treatment was unable to induce a significant improvement of cartilage degradation vs the saline control in the experimentally induced knee OA. However, subcutaneous injections of 1 mg/kg CDPS induced a marked inhibition (P<0.05) of osteophyte formation. Additionally, a significant reduction of cartilage degradation revealed an overall chondroprotective effect of CDPS at a concentration of 1 mg/kg. No significant effects on weight gain were noted. CONCLUSIONS Systemic administration of CDPS is able to protect cartilage in vivo and can therefore be considered as a chondroprotective agent with structure modifying capacities.

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