C. Geli

Association Between Nailfold Capillaroscopy Findings and Pulmonary Function Tests in Patients with Systemic Sclerosis

Objective. To determine whether there is an association between different capillaroscopic findings and pulmonary function tests in systemic sclerosis (SSc). Methods. We did a retrospective observational study in a cohort of patients with SSc and early SSc. Patients with at least 1 nailfold videocapillaroscopy (NVC) magnified 120× were included. Pathological findings were giant capillaries, angiogenesis, and density loss. Findings were compared with lung function values: percent expected value of forced vital capacity (FVC), DLCO, and FVC/DLCO ratio. Other variables collected were sex and SSc type, and the presence of digital ulcers (DU), interstitial lung disease (ILD), scleroderma renal crisis, and/or pulmonary hypertension (PH). Results. Of 136 patients with SSc, 85 had undergone an NVC. The frequency of ILD, DU, and PH was 24.1%, 28.7%, and 17.2%, respectively. Data analysis showed that patients with density loss had worse FVC% (86.91 ± 19.42 vs 101.13 ± 16.06, p < 0.01) and DLCO% (71.43 ± 21.19 vs 85.9 ± 19.81, p < 0.01) compared to those without. Conclusion. Patients with loss of density present worse FVC and DLCO values. Prospective studies are warranted to determine whether NVC is useful for studying pulmonary function in SSc.

Rituximab-induced interleukin-15 reduction associated with clinical improvement in rheumatoid arthritis

Rituximab therapy alters all aspects of B‐cell participation in the disturbed immune response of rheumatoid arthritis patients. To determine the impact of B‐cell depletion on other immune compartments, we analysed levels of soluble and surface interleukin‐15 (IL‐15) along with the frequency of IL‐15‐related subsets after rituximab treatment. We then studied the correlation of observed changes with clinical activity. Heparinized blood samples from 33 rheumatoid arthritis patients were collected on days 0, 30, 90 and 180 after each of three rituximab cycles. Serum cytokine levels were determined by ELISA. Interleukin‐15 trans‐presentation was analysed by cytometry. Flow cytometry with monoclonal antibodies was performed to analyse circulating cell subsets. Interleukin‐15 was detected in the serum of 25 patients before initiating the treatment. Rituximab then progressively reduced serum IL‐15 (138 ± 21 pg/ml at baseline, 48 ± 18 pg/ml after third cycle, P = 0·03) along with IL‐17 (1197 ± 203 pg/ml at baseline, 623 ± 213 pg/ml after third cycle, P = 0·03) and tended to increase the frequency of circulating regulatory T cells (3·1 ± 1 cells/μl at baseline, 7·7 ± 2 cells/μl after third cycle). Rituximab also significantly decreased IL‐15 trans‐presentation on surface monocytes of patients negative for IL‐15 serum (mean fluorescence intensity: 4·82 ± 1·30 at baseline, 1·42 ± 0·69 after third cycle P = 0·05). Reduction of serum IL‐15 was associated with decrease in CD8+ CD45RO+/RA+ ratio (1·17 ± 0·21 at baseline, 0·36 ± 0·06 at third cycle, P = 0·02). DAS28, erythrocyte sedimentation rate and C‐reactive protein correlated significantly with CD8+ CD45RO+/RA+ ratio (R = 0·323, R = 0·357, R = 0·369 respectively, P < 0·001). Our results suggest that sustained clinical improvement after rituximab treatment is associated with IL‐15/memory T‐cell‐related mechanisms beyond circulating B cells.

Adalimumab regulates intracellular TNFα production in patients with rheumatoid arthritis.

IntroductionAdalimumab is a fully human anti–tumor necrosis factor α (anti-TNFα) monoclonal antibody that specifically blocks the interaction of TNFα with its receptors. It binds both soluble and transmembrane TNFα. We hypothesized that blocking these TNFα signals regulates the altered TNFα production in rheumatoid arthritis (RA) patients.MethodsWe compared, by flow cytometry, Toll-like receptor induction levels of membrane and intracellular TNFα in monocytes (iTNFα + CD14+ cells) from 12 patients before and after adalimumab treatment with those from 5 healthy donors.ResultsBefore starting the treatment, the percentage of iTNFα+ CD14+ cells in the RA patients was significantly lower than that in healthy donors (mean ± SEM = 33.16 ± 4.82% vs 66.51 ± 2.4%, P < 0.001). When we added in vitro TNFα to healthy donor culture cells, levels of iTNFα+ CD14+ cells decreased, suggesting that the TNFα signal was responsible for the iTNFα+ CD14+ cell downregulation observed in the RA patients. After 2, 6 and 12 adalimumab injections, we observed significant blocking of membrane and soluble TNFα and a progressive increase in iTNFα+ CD14+ cells in ten patients with a good to moderate response as defined by the European League Against Rheumatism (EULAR) criteria. Levels of iTNFα+ CD14+ cells after 12 injections in these 10 patients were comparable to levels in healthy donors. In two patients, iTNFα+ CD14+ cell upregulation was not observed, and their EULAR-defined responses had not improved. The first patient developed antiadalimumab antibodies, explaining why adalimumab was not able to block membrane and soluble TNFα. In the second patient, adalimumab was discontinued because of adverse effects, which led to a decrease in iTNFα+ CD14+ cells to levels measured before treatment.ConclusionsOur findings suggest that adalimumab treatment in RA patients can return iTNFα levels to those of healthy donors. This effect was not observed in the presence of neutralizing antiadalimumab antibodies.

Disfunción tiroidea en mujeres con sospecha de fibromialgia

Fundamento y objetivo: La fibromialgia (FM), por su prevalencia, morbilidad y tasa de frecuentacion, representa un problema de salud y genera un elevado consumo de recursos sanitarios. La medida de tirotropina (TSH) en el suero se recomienda como prueba complementaria de primera linea para descartar hipotiroidismo como anomalia simuladora de la enfermedad. El objetivo fue analizar, en mujeres con sospecha de FM, la prevalencia de disfuncion tiroidea (DT), la frecuencia de solicitud analitica de tirotropina, el efecto del tratamiento con levotiroxina y si se justifica o no el escrutinio de DT. Pacientes y metodos: Estudio descriptivo transversal. Desde enero de 2001 a octubre de 2004 se estudio a 400 mujeres consecutivas con sospecha de FM y a 384 controles. La medida de tirotropina se uso como primera prueba para detectar DT. Resultados: La prevalencia de DT en la sospecha de FM (40/400; 10%, intervalo de confianza [IC] del 95%, 7-13%) no difirio de la de controles (46/384; 12%, IC del 95%, 9-15%); tampoco al comparar distintos tipos y grados de DT. En la sospecha de FM, la DT fue mas prevalente (p = 0,001) en portadoras (12%) que en no portadoras (5%) de enfermedad del tejido conectivo. La DT mas frecuente fue el hipotiroidismo subclinico (5,5% en FM y 6,7% en controles), y en el 93% de casos nuevos la concentracion de TSH fue < 10 mUI/l. La FM persistio en todas las pacientes hipotiroideas al lograrse el eutiroidismo. En 360 pacientes eutiroideas con sospecha de FM se realizaron 870 determinaciones de TSH. Conclusiones: En mujeres con sospecha de FM, la prevalencia de DT no difiere de la descrita en la poblacion general, no parece justificarse el escrutinio de DT en no portadoras de enfermedad de riesgo y la demanda analitica es en muchos casos excesiva; el tratamiento del hipotiroidismo no influye en la FM .BACKGROUND AND OBJECTIVE Due to its prevalence, morbidity, and frequency rate, fibromyalgia (FM) represents a health problem and produces high healthcare resource utilization. Serum thyrotropin (TSH) measurement is recommended as a first-line laboratory test to exclude hypothyroidism as a cause of FM syndrome. The aim of this study was to analyze the prevalence of thyroid dysfunction (TD), the frequency of TSH measurement, the effect of levothyroxine treatment, and whether screening for TD is justified in women with suspected FM. PATIENTS AND METHODS A cross-sectional descriptive study was performed in 400 consecutive female outpatients with suspected FM and in 384 controls from January 2001 to October 2004. TSH measurement was used as the first line test to detect TD. RESULTS The prevalence of TD in patients with suspected FM (40/400; 10%; 95% CI: 7-13%) and controls was similar (46/384; 12%; 95% CI: 9-15%). No differences were found in the types and grades of TD. The prevalence of TD was higher in patients with suspected FM and connective tissue diseases (12%) than in those without these diseases (5%). The most frequent TD was subclinical hypothyroidism (5.5% in suspected FM and 6.7% in controls), and in 93% of these cases TSH concentrations were <10 mIU/L. FM persisted in all women with hypothyroidism even after euthyroidism was achieved with levothyroxine. A total of 870 TSH determinations were performed in 360 euthyroid patients with suspected FM. CONCLUSIONS The prevalence of TD in women with suspected FM does not differ from that in the general population. Screening for TD does not appear to be justified in women without diseases that increase their risk. In many cases the request for thyroid function tests is excessive. Treatment for hypothyroidism does not affect FM.

Estudio VARIAR: VAloración de la eficacia y seguridad a corto plazo en artritis reumatoide del uso de RItuximab comparado con Antagonistas del factor de necrosis tumoral alfa en segunda línea terapéutica en pacientes con artritis reumatoide Refractarios a un primer antagonista del factor de necrosis tumoral alfa

OBJECTIVE to compare the short-term efficacy and safety of rituximab (RTX) therapy versus anti-TNF in rheumatoid arthritis (RA) patients after discontinuation of a first anti-TNF agent. METHODS prospective observational multicenter study in the clinical practice setting, involving patients with severe RA refractory to a first anti-TNF agent, who received either RTX or a second anti-TNF (2TNF), comparing the efficacy endpoints, EULAR response (Good/Moderate) and safety at 6 months. RESULTS 103 patients enrolled, 82 completed 6-month follow-up, 73.7% women. Baseline data for RTX and 2TNF groups, respectively: TJC, 8.6 and 6.6; SJC, 8.8 and 7.5; DAS28 score, 5.45 (±1.28) and 5.18 (±1.21) (p=0.048), ESR, 41 and 38.7mmHg; and HAQ, 1.2 and 1.0. Improvement was observed in all parameters, with no significant differences (except for a more marked reduction in ESR with RTX). There were no serious adverse events. CONCLUSIONS RTX use as second-line therapy after anti-TNF failure led to improvements in the efficacy and functional variables at 6 months, with no serious adverse events. These results were comparable to those observed in patients who used a second anti-TNF agent in the same clinical scenario.

SAT0606 Impact of Musculoskeletal Ultrasound in Treatment Decision in Routine Daily Care of Rheumatoid Arthritis (Impulsar Study): Table 1

Background Remission or low disease activity is the therapeutic target in the ACR-EULAR recommendation for the management of rheumatoid arthritis (RA). In multiple studies, musculoskeletal ultrasound (US) has shown to be more reliable and sensitive than physical examination in both the diagnosis and the assessment of RA activity. However, the real impact of this technique on routine daily care of RA and treatment decisions has not been studied. Objectives To assess the proportion of therapeutic decisions that are modified by the results of the US examination in patients with RA. To determine which group of patients would get more benefit from a musculoskeletal US to optimize treatment. Methods Seventy eight consecutive patients diagnosed with RA by ACR 1987 criteria and visited between July and November 2014, were included. All patients were initially visited by their usual rheumatologist and a therapeutic decision was made according to physical examination and clinical and laboratory findings. Subsequently, a musculoskeletal US was performed by an expert sonographer of our center and the usual rheumatologist was asked to reassess his therapeutic decision in light of the US findings. We classified the change in the therapeutic attitude as: negative (maintenance of therapeutic attitude) and positive (increase or reduction in treatment, compared to the initial decision). Demographic, clinical and laboratory data were collected from the clinical history and activity scores were calculated. Results Clinical, demographic, laboratory, treatment and activity score data are shown in table below. In 29 patients [37.2% (95% CI 26.5 to 48.9)] the findings in the US examination conditioned a change in the therapeutic decision of the usual rheumatologist. In 18 patients (62.07%) the change was towards an intensification of treatment, while in 11 patients (37.93%) a decrease was possible. Change of treatment was more frequent in patients with intermediate disease activity (mild and moderate activity) than in those with extreme activities (remission and high activity), 41.4% vs 25%, although this difference was not statistically significant. A higher frequency of change was found in men (53.8% vs 33.8%) and erosive RA forms (43.6% vs 21.7%), but the results did not reach statistical significance.Table 1 Total (n=78) Age (years ± SD) 63,27 (±12,94) Disease duration (years ± SD) 15,49 (±10,66) Female (%) 65 (83,33%) Erosive form (%) 55 (70,51%) RF positive (%) 49 (62,82%) Anti-CCP positive (%) 59 (75,64%) DMARDs  Methotrexate 33 (42,31%)  Leflunomide 5 (6,41%)  Salazopyrin 7 (8,97%)  Hydroxychloroquine 2 (2,56%) Biologic therapies  Anti-TNF 14 (17,95%)  Others 11 (14,10%) DAS28-ESR (mean ± SD) 3,19 (±1,09) DAS28 activity  high 1 (1,28%)  moderate 36 (46,15%)  mild 22 (28,20%)  remission 19 (24,36%) Conclusions Musculoskeletal ultrasound, when added to routine rheumatologic investigation, is an important tool for treatment decisions in the routine daily care of rheumatoid arthritis. Patients with intermediate activities of the disease might get more benefit from the use of an US examination. Disclosure of Interest None declared

AB0692 Radiographic Damage in A Group of Patients with Axial Spondyloarthritis

Background Recent studies in the field of axial spondyloarthropathies (SpA-ax) have shown a group of patients with chronic lower back pain without evidence of radiographic damage (non-radiographic axial spondyloarthritis). Currently, data is lacking that would confirm whether it is an early stage of the disease or a group of SpA-ax that is different, in which time of progression and radiographic damage show no relationship. Objectives Describe our cohort of patients diagnosed with radiographic axial spondyloarthritis. Assess whether those with both sacroiliac and spinal radiographic involvement have a longer duration of the disease and the relationship between this most-affected group and the different items that constitute the ASAS criteria for SpA-ax. Methods All patients diagnosed with SpA-ax by ASAS or NY criteria, who were seen in a monographic consultation of spondyloarthritis of our center between January 2012 and December 2013, were reviewed. Only those with sacroiliitis of grade II or higher were included; patients who did not have spinal radiographs were excluded. The following clinical and laboratory variables were collected from clinical history: age, sex, duration of disease, inflammatory back pain, arthritis, enthesitis, uveitis, dactylitis, psoriasis, inflammatory bowel disease, positive response to NSAIDs, family history of SpA, HLA-B27 and elevated CRP. The presence of 3 or more syndesmophytes in the dorsal and/or lumbar region was considered as spinal involvement. For statistical analysis, students t-test, chi-square test or Fishers exact test were performed where applicable. Results Of the 72 patients diagnosed with SpA-ax, 58 met the inclusion and exclusion criteria. The mean age of the study patients was 53.69 years and 69% were men. The mean disease duration was 19.48 years and 36 patients had spinal involvement. Only the age of patients, the sex and the duration of the disease showed significant results regarding the structural damage (see table). Table 1 Total Spinal X-ray − Spinal X-ray + p (n=58) (n=22) (n=36) Age, years 53.69±13.41 47.36±13.05 57.56±13.45 *p=0.006 Disease duration, years 19.48±12.06 14.86±9.57 22.31±12.67 *p=0.021 % male 40 (69) 11 (50) 29 (80.5) *p=0.02 Inflammatory back pain (%) 48 (82.75) 20 (90.9) 28 (77.8) p=0.29 Arthritis (%) 31 (53.45) 11 (50) 20 (55.5) p=0.79 Enthesitis (%) 25 (43.1) 9 (40.9) 16 (44.4) p=1.00 Uveitis (%) 12 (20.7) 6 (27.3) 6 (16.7) p=0.50 Dactylitis (%) 6 (10.3) 3 (13.6) 3 (8.3) p=0.70 Psoriasis (%) 20 (34.5) 10 (45.4) 10 (27.8) p=0.25 Inflammatory bowel disease (%) 2 (3.45) 1 (4.5) 1 (2.8) p=1.00 Good response to NSAIDs (%) 47 (81) 20 (90.9) 27 (75) p=0.29 Family history of SpA (%) 13 (22.4) 4 (18.2) 9 (25) p=0.75 HLA-B27 positive (%) 33 (56.9) 12 (54.5) 21 (58.3) p=0.78 CRP >5mg/l (%) 45 (77.6) 15 (68.2) 30 (83.3) p=0.21 * p<0.05. Conclusions In our cohort, patients with more severe radiographic involvement were those of a longer disease duration and an older age, with a predominance of men. No significant differences for the remaining assessed variables were found, including signs of inflammation and HLA-B27, which were similar in both groups of patients. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.4483

AB0826 Hyperuricemic patients with systemic sclerosis do not present higher incidence of pulmonary hypertension but have worse echocardiographic parameters

Background Uric acid (UA) serum levels are increased in conditions that affect the oxidative metabolism. Several studies have demonstrated increased UA levels in patients with pulmonary hypertension (PH) and its relation to prognosis. There are few studies demonstrating the clinical significance of hyperuricemic in patients with PH secondary to systemic sclerosis (SSc). Objectives To determine whether patients with SSc and PH have a higher frequency of hyperuricemica and to determine if there is greater frequency of PH in hyperuricemic and SSc patients. Methods Retrospective review of cohort of patients with SSc from rheumatology unit of a tertiary university hospital. Hyperuricemia was considered if UA levels were higher than 6,8 mg/dl and PH in either the presence of echocardiographic signs of PH or pulmonary artery pressure (PAP) >40mmHg. The following variables were collected: sex, age at diagnosis, type of SSc (limited, diffuse, earlySSc or without skin involvement), presence or absence of: digital ulcers (DU), sclerodermic renal crisis (SRC), interstitial lung disease (ILD), use of hyporuricemic therapy, colchicine and NSAIDs. Uric acid levels, renal and respiratory function parameters and echocardiographic parameters were recorded. To compare groups of qualitative variables chi-square or Fisher test were used, and T-test for quantitative variables. Statistical significance level was set to p values ≤0.05. Results A total of 136 patients with SSc (93,4% female, age at diagnosis 51,02±15,51 years) were included. Ninety five out of 136 presented limited SSc, 21 diffuse SSc, 19 early SSc and 1 sine scleroderma. One third (31,6%) of the patients presented DU along their disease, 28,7% ILD, 21,3% PH and 2,2% SRC. Patients with PH presented ILD more frequently (50% vs 23,36% p =0.006), but the frequency of DU and SRC were not increased. Parameters of DLCO (Diffusing capacity for carbon monoxide)and FVC (Forced vital capacity) were significantly lower in patients with PH (56,7±19,1% vs 80,13 vs 19,13% and 77,86±23,42 vs. 95,09±18,3 p <0,01). Higher ratio FVC/DLCO and thicker than the IVT (11,52±3,16 vs 10,02±2,18 p =0.03) were observed in these patients. No differences in the levels of UA in both groups were detected. Patients with hyperuricemia did not have higher frequency of PH (35,7 vs 21,5%, p ns) than those without, but they did show a higher frequency of SRC (p <0.05). When comparing different echocardiographic parameters, patients with hyperuricemia had higher values of estimated PAP (45,5±8,081 vs 33,41±9,87 mmHg, p =0,024), lower TAPSE (1,6±0,14 vs 2,52±1,78 cm, p =0,01) and increased IVT thickness (12,44±2,78 vs 10,25±2,3 mm, p<0.05). Conclusions Patients with PH had a higher ILD frequency. There was no difference in the frequency of hyperuricemia between groups. Hyperuricemic patients did not show a higher PH frequency, nevertheless they showed worse echocardiographic parameters. The presence hyperuricemia was also associated with higher frequency of SRC. Furthers works are needed to evaluate the effects of UA in SSc. Disclosure of Interest None Declared

AB0806 Rituximab in clinical practice for the treatment of interstitial lung disease refractory to cyclophosphamide in patients with diffuse systemic sclerosis

Background Systemic sclerosis or scleroderma (SSc) is a connective tissue disease which frequently presents lung affectation, being the principal cause of death in these patients. Currently, only cyclophosphamide (CyC) has shown efficiency to treat this complication. However, this efficiency is modest and not kept through the time. Several medicines have been tested for the treatment of this complication with controversial results. Rituximab (RTX) seems to show improvement in patients with SSc and Interstitial Lung Disease (ILD) refractory to others treatments, but there are not pivotal assays in this regard and the experience is limited. Objectives To study the evolution of Pulmonary Function Test (PFT) in patients with SSc affected by ILD refractory to usual treatment and have made at least one cycle of Rituximab. Methods Multicenter observational prospective study in patients with ILD-SSc was performed. These patients had one cycle of two Rituximab infusions for ILD and previously had realized CyC, azathioprine or mycophenolic acid with treatment failure. We evaluated the following data: gender, age, onset age of Raynaud’s phenomenon, age at diagnosis of SSc, age at diagnosis of ILD, ILD type, total dose of CYC, use of concomitants steroids, and other immunosuppressive agents. PFT outcome after each therapy and after 4 months of treatment with RTX was included. Results We collected the data of four patients who realized one complete cycle of treatment with RTX. Patients were women and presented diffuse cutaneous shape with antitopoisomerase I antibodies. The radiologic affectation was Non-Specific Interstitial Pneumonia (NSIP) in all cases. Patient’s characteristics are showed in table 1. The patient who presented the best response to RTX (Patient 4) had the highest dose of CyC accumulated previously. As a whole, patients presented a worsening of the predicted value of FVC and DLCO after treatment with CyC. Four months later of RTX infusion, we did not observe any worsening in the values of FVC beside of a trend to improve the values of DLCO. The best response in concern to respiratory function parameters was not related with taking concomitant or accumulated dose of other drugs different to CYC. Age Age at diagnosis Age at ILD diagnosis FVC at ILD diagnosis (%) DLCO at ILD diagnosis (%) FVC post CyC (%) DLCO post CyC (%) FVC post RTX (%) DLCO post RTX (%) Cumulative CyC dose (g) Patient 1 51 31 39 53 80 40 28.9 51.4 31.4 21 Patient 2 35 28 28 47.8 38 38.6 16 37.5 15.7 20 Patient 3 65 58 58 49.8 40.8 37.9 30.7 15 Patient 4 52 47 47 62 55 56 45 60 61 27 Mean ± SD 50.75±12.28 39±13.49 43±12.65 53.15±6.28 53.45±19.2 44.87±9.67 29.97±14.53 44.9±13.25 36.03±23 20.43±5.23 Conclusions Rituximab could be an alternative to the treatment and stabilization for interstitial lung disease in patients with SSc, however experience remains limited. Disclosure of Interest None Declared

AB0189 Polymorphisms in genes involved in the metotrexate action mechanism. are they associated with response/toxicity of the drug?

Background Rheumatoid arthritis (RA) is a chronic, systemic, inflammatory autoimmune disease of unknown etiology. Methotrexate (MTX) is the first-line treatment option for newly diagnosed RA patients. However, only 50–70% of the patients will respond to MTX therapy and up to one third will discontinue treatment because of toxicity. Objectives Studying SNPs (single nucleotide polymorphisms) described in the literature for its possible role as biomarkers of response and / or toxicity to MTX, in Spanish patients diagnosed with rheumatoid arthritis. Methods We analyzed 27 TagSNPs in 5 candidate genes (DHFR, TYMS, MTHFR, ATIC and CCND1) involved in the action mechanism of MTX. We studied its association with the therapy-related efficacy and toxicity. One hundred and twenty-four adult patients with RA treated with MTX monotherapy were studied. TagSNPs within these genes were selected using bioinformatic tools and were genotyped using a 48.48 dynamic array on the BioMark system. Toxicity was measured as the time interval that MTX was administered. Efficacy was assessed using the DAS-28 EULAR response criteria. Results Clinical data of the patients are shown in Table 1. The univariate analyses showed significant association with toxicity in the dominant model with two TagSNPs in the ATIC gene: rs10197559 (P=0.05) and rs16853826 (P=0.04). Two TagSNPs in the MTHFR gene showed significant association with response in the dominant model: rs11121832 (P=0.02) and rs17421511 (P=0.02). Conclusions Polymorphisms in the ATIC and MTHFR genes may be considered as putative pharmacogenetic markers in RA patients treated with MTX on monotherapy. References Kinder AJ, Hassell AB, Brand J, Brownfield A, Grove M, Shadforth MF. The treatment of inflammatory arthritis with methotrexate in clinical practice: treatment duration and incidence of adverse drug reactions. Rheumatology 2005;44:61–6 Wessels JA, van der Kooij SM, le Cessie S, Kievit W, Barerra P, Allaart CF, et al. A clinical pharmacogenetic model to predict the efficacy of methotrexate monotherapy in recent-onset rheumatoidarthritis. Pharmacogenetics Collaborative Research Group. Arthritis Rheum 2007; 56: 1765–75 Acknowledgements Societat Catalana de Reumatologia. Disclosure of Interest None Declared