E. Martín Mola

Finalisation and validation of the rheumatoid arthritis impact of disease score, a patient-derived composite measure of impact of rheumatoid arthritis: a EULAR initiative

Objective A patient-derived composite measure of the impact of rheumatoid arthritis (RA), the rheumatoid arthritis impact of disease (RAID) score, takes into account pain, functional capacity, fatigue, physical and emotional wellbeing, quality of sleep and coping. The objectives were to finalise the RAID and examine its psychometric properties. Methods An international multicentre cross-sectional and longitudinal study of consecutive RA patients from 12 European countries was conducted to examine the psychometric properties of the different combinations of instruments that might be included within the RAID combinations scale (numeric rating scales (NRS) or various questionnaires). Construct validity was assessed cross-sectionally by Spearman correlation, reliability by intraclass correlation coefficient (ICC) in 50 stable patients, and sensitivity to change by standardised response means (SRM) in 88 patients whose treatment was intensified. Results 570 patients (79% women, mean±SD age 56±13 years, disease duration 12.5±10.3 years, disease activity score (DAS28) 4.1±1.6) participated in the validation study. NRS questions performed as well as longer combinations of questionnaires: the final RAID score is composed of seven NRS questions. The final RAID correlated strongly with patient global (R=0.76) and significantly also with other outcomes (DAS28 R=0.69, short form 36 physical −0.59 and mental −0.55, p<0.0001 for all). Reliability was high (ICC 0.90; 95% CI 0.84 to 0.94) and sensitivity to change was good (SRM 0.98 (0.96 to 1.00) compared with DAS28 SRM 1.06 (1.01 to 1.11)). Conclusion The RAID score is a patient-derived composite score assessing the seven most important domains of impact of RA. This score is now validated; sensitivity to change should be further examined in larger studies.

III Actualización del Consenso de la Sociedad Española de Reumatología sobre terapia biológica en la artritis reumatoide

como en el caso de los antagonistas del factor de necrosis tumoral (TNF), en los pacientes con AR de inicio reciente. Es evidente que la disponibilidad cada vez mayor de agentes biológicos ha mejorado sensiblemente nuestra capacidad de inducir remisión en muchos pacientes con AR y de modificar significativamente su evolución en otros. No obstante, por su alto coste y la todavía limitada información sobre sus posibles efectos secundarios a largo plazo, es necesario evitar su uso indiscriminado. Por ello es aconsejable integrar su uso dentro de una estrategia terapéutica de la enfermedad en general. El presente Documento de Consenso de la Sociedad Española de Reumatología (SER) es una actualización del último documento elaborado con los mismos fines en 20044. Estas recomendaciones deben servir de referencia tanto para los reumatólogos como para todos quienes, desde otras posiciones, tengan interés en el tratamiento de la AR.

Osteoarticular infection in intravenous drug abusers: influence of HIV infection and differences with non drug abusers.

OBJECTIVES--To determine (a) the influence of HIV in developing osteoarticular infections in intravenous drug abusers (IVDAs) and (b) the differences between the clinical features of osteoarticular infections in IVDAs and a control group of non-IVDAs. METHODS--A comparative study of the clinical features of osteoarticular infections in all HIV positive and HIV negative IVDAs admitted to the departments of rheumatology and internal medicine during a 10 year period was carried out. The joint infections of all IVDAs, irrespective of HIV status, were compared with those of a control group of non-IVDAs lacking risk factors for HIV infection. RESULTS--A total of 482 HIV positive and 85 HIV negative IVDAs was studied, in whom 25 (5%) and six (7%) osteoarticular infections were found respectively. There were no differences in age, sex, joints affected, and causative agents between these two groups. A comparison of the 31 (5.5%) osteoarticular infections in all IVDAs with 21 infections in 616 (3.4%) non-IVDAs showed significant differences in the mean age (27.5 v 54), the frequency of affection of the axial joints (hip, sacroiliac, and sternocostal joints) (64.5% v 16.6%), and in the incidence of Candida albicans (19% v 0%). CONCLUSIONS--(1) HIV may not predispose to osteoarticular infections in IVDAs. (2) The hip, sacroiliac, and sternocostal joints (axial joints) were most commonly affected in IVDAs. (3) In Spain, unlike other countries, Gram positive bacteria and C albicans seem to be predominant agents in osteoarticular infections in IVDAs, with a low incidence of Gram negative bacteria.

Abnormalities in the bone mineral metabolism in HIV-infected patients

ObjectiveTo evaluate bone mineral metabolism in HIV infected and asymptomatic patients receiving highly active antiretroviral therapy (HAART) containing protease inhibitors (PI) and naïve patients.MethodsWe studied 30 asymptomatic HIV infected male patients, 13 in the naive group and 17 in the IP group, both without differences in demographics characteristics. We excluded women and patients with any known factor associated to osteopenia. We did a nutritional questionnaire, a DEXA scan in lumbar spine and femur, a study of CD4 lymphocytes, viral load and an analysis of bone formation and resorption markers in all patients. We compared vitamin D and PTH levels with a control group of healthy male volunteers age-pareated. For the statistical analysis we used the SPSS program.ResultsOsteopenia was present in 17/30 (57%), 8/13 (61.5%) in the naïve group and 9/17 (53%) in the PI group (not significant differences). We found a vitamin D deficiency in 86% of patients, with mean serum levels that was found to be significantly lower than those from a healthy control group (p=0.04). Testosterone level was significantly related to bone mineral density in lumbar spine (p≤0.05).ConclusionsHIV may be an individual risk factor in bone disorders, requiring calcium and vitamin D supplementation.

The safety and efficacy of adding etanercept to methotrexate or methotrexate to etanercept in moderately active rheumatoid arthritis patients previously treated with monotherapy

Objective: To determine if adding etanercept (ETN) to methotrexate (MTX) or MTX to ETN for 52 weeks in rheumatoid arthritis (RA) patients with moderate disease activity provides higher efficacy. Methods: All patients (n = 227) received open-label ETN 25 mg subcutaneously twice-weekly and MTX orally up to 20 mg weekly for 52 weeks and had completed a 3-year study in which patients received MTX, ETN or combination therapy. Endpoints were based on Disease Activity Score (DAS) and European League Against Rheumatism (EULAR) responses. Results: Patients previously receiving combination therapy (Combination group; n = 96) had a lower disease activity at baseline. The mean DAS for those previously receiving MTX (ETN-added group; n = 55) and previously receiving ETN (MTX-added group; n = 76) were in the moderate disease activity range at baseline; Combination patients had a low disease activity. The greatest increase in DAS remission rates from baseline to week 52 was in the ETN-added group (23.6% to 41.8%, p<0.01), although Combination (37.6% to 50.0%, p<0.01) and MTX-added (26.7% to 36.8%, p = NS) also demonstrated improvements. DAS low disease activity and EULAR responses showed similar results. No new safety issues were identified. Conclusion: RA patients who were partial responders to long-term MTX or etanercept monotherapy obtained a higher efficacy with combination therapy. Responses achieved by patients with combination therapy after 3 years in the previous study were sustained or improved during the fourth year of treatment. This trial supports the higher therapeutic effect of combination treatment with etanercept and MTX in RA patients with moderate disease activity despite monotherapy with one of the two agents.

Multi-language translation and cross-cultural adaptation of the OARSI/OMERACT measure of intermittent and constant osteoarthritis pain (ICOAP)

AIM To conduct a multi-language translation and cross-cultural adaptation of the Intermittent and Constant OsteoArthritis Pain (ICOAP) questionnaire for hip and knee osteoarthritis (OA). METHODS The questionnaires were translated and cross-culturally adapted in parallel, using a common protocol, into the following languages: Czech, Dutch, French (France), German, Italian, Norwegian, Spanish (Castillan), North and Central American Spanish, Swedish. The process was conducted following five steps: (1)--independent translation into the target language by two or three persons; (2)--consensus meeting to obtain a single preliminary translated version; (3)--backward translation by an independent bilingual native English speaker, blinded to the English original version; (4)--final version produced by a multidisciplinary consensus committee; (5)--pre-testing of the final version with 10-20 target-language-native hip and knee OA patients. RESULTS The process could be followed and completed in all countries. Only slight differences were identified in the structure of the sentences between the original and the translated versions. A large majority of the patients felt that the questionnaire was easy to understand and complete. Only a few minor criticisms were expressed. Moreover, a majority of patients found the concepts of constant pain and pain that comes and goes to be of a great pertinence and were very happy with the distinction. CONCLUSION The ICOAP questionnaire is now available for multi-center international studies.

FRI0089 Assessing maintenance of remission with reduced dose etanercept plus methotrexate, methotrexate alone, or placebo in patients with early rheumatoid arthritis who achieved remission with etanercept and methotrextate: the prize study

Background During Phase 1 of the 52 wk open-label PRIZE study treatment of patients (pts) with early (mean 6 mos.) moderate-severe rheumatoid arthritis (RA), who were methotrexate (MTX)/biologic naïve, with 50 mg etanercept (ETN) + 10-25 mg MTX yielded a 70% remission rate with no significant radiographic progression.1 Pts achieving remission in Phase I were randomized to a double-blind 39-wk period of reduced (25mg) ETN + MTX or withdrawn (MTX alone or placebo, PBO) therapy (PRIZE Phase 2). Objectives To assess sustained remission (DAS28 and ACR/EULAR Boolean [AEB]), other clinical, radiographic, and safety outcomes in pts subsequently treated with reduced dose ETN or PBO after remission induction during PRIZE Phase 1. Methods Pts achieving DAS28 remission by wk 52 (≤3.2 at wk 39, <2.6 at wk 52) in Phase 1 (n=193) were randomized 1:1:1 to ETN25/MTX: MTX + PBO injection: PBO capsules + PBO injection at wk 52. Pts with DAS28>3.2 (> low disease activity, LDA) received corticosteroid boosts at wks 56 or 64; pts not achieving LDA at the next visit withdrew. Remission and other standard clinical outcomes were assessed. Odds ratios and significance were determined by logistic regression models. Results ETN/MTX resulted in a significantly higher proportion of pts in sustained and AEB remission than MTX alone or PBO. More ETN/MTX treated pts achieved DAS28 LDA than PBO. Over Phase 2 radiographic progression (mTSS >0.5) occurred in <12% of pts, with no significant difference between treatment arms; at Phase 1 baseline the mTSS scores were 8.06, 8.46 and 7.59 for ETN25/MTX, MTX and PBO, with changes of 0.44, -0.5 and 1.41 by last observations in Phase 2 (LOCF), indicating no clinically relevant radiographic progression in any of these treatment groups ETN/MTX treatment resulted in more pts achieving ACR50 and 70 than PBO. There were no unexpected safety findings. Conclusions Of the moderate-severe early RA pts achieving DAS28 remission during a 52 wk induction (50 mg ETN/MTX in PRIZE Phase 1), 63.5% maintained remission (DAS28<2.6 at wk 76 & 91 visits) with ETN25/MTX, 38.5% with MTX and 23% with PBO over 39 subsequent wks. There was no significant radiographic progression in any treatment group. There were no unexpected safety findings. References Emery P et al. American College of Rheumatology/ARHP Annual Scientific Meeting – 2012;64(10):S160; Abstract 368. Acknowledgements The PRIZE study was funded by Pfizer Inc. Disclosure of Interest P. Emery Consultant for: Abbott, Bristol-Myers Squibb, Merck, Novartis, Pfizer Inc, Roche-Chugai, UCB Pharma Ltd, M. Hammoudeh Consultant for: Pfizer Inc, Roche, Abbott Laboratories, O. FitzGerald Consultant for: Bristol-Myers Squibb, Roche, Abbott Laboratories, Pfizer Inc, UCB Pharma Ltd, B. Combe Consultant for: Bristol-Myers Squibb, Merck, Pfizer Inc, Roche-Chugai, UCB Pharma Ltd, E. Martin Mola Consultant for: Pfizer Inc, Roche, Celgene Ltd, UCB Pharma Ltd, Speakers bureau: Pfizer Inc, Roche, UCB Pharma Ltd, J. Bukowski Employee of: Pfizer Inc, R. Pedersen Employee of: Pfizer Inc, T. Williams Employee of: Pfizer Inc, S. Gaylord Employee of: Pfizer Inc, B. Vlahos: None Declared

Inhibition of radiographic progression with combination etanercept and methotrexate in patients with moderately active rheumatoid arthritis previously treated with monotherapy

OBJECTIVE To determine the effect of changing from etanercept or methotrexate monotherapy to etanercept plus methotrexate combination therapy on radiographic progression in rheumatoid arthritis (RA) patients. METHODS Patients enrolled in this 1-year open-label study previously completed a 3-year blinded study in which they received methotrexate or etanercept monotherapy or the combination of both. All patients received the combination of etanercept 25 mg subcutaneously twice weekly plus oral methotrexate up to 20 mg/week. The primary radiographic endpoint was a change in modified total Sharp score (TSS), as assessed by blinded readers. RESULTS At baseline, patients previously receiving methotrexate monotherapy (etanercept-added, n = 52) or etanercept monotherapy (methotrexate-added, n = 68) had moderate disease activity levels (mean disease activity score (DAS) of 2.6 and 2.5, respectively), whereas patients previously receiving combination therapy (n = 90) had a low disease activity level (mean DAS of 2.0). The addition of etanercept to methotrexate monotherapy resulted in a significant reduction in radiographic progression (p<0.05). Mean TSS changes in the previous year versus the current year were +1.79 versus +0.25 for the etanercept-added group (p<0.05); +0.51 versus -0.18 for the methotrexate-added group (NS) and +0.42 versus +0.24 for the combination group (NS). CONCLUSION In these RA patients with on average moderate disease activity despite previous methotrexate monotherapy, combination treatment with etanercept and methotrexate inhibited radiographic progression and improved radiographic outcomes. These data, in conjunction with the previously published clinical data, support the use of combination therapy in RA patients with moderate disease activity.

Evaluación del dolor musculoesquelético crónico en la población adulta española y su manejo en Atención Primaria: actitudes, percepción del estado de salud y uso de recursos sanitarios

Introduccion El presente estudio procede de una encuesta europea promovida por el Arthritis Action Group en 8 paises con el objetivo de conocer la prevalencia e impacto en la calidad de vida del dolor musculoesqueletico cronico (DMC). Se muestran los resultados en Espana. Metodos Estudio transversal realizado en Espana mediante encuesta telefonica a 200 medicos de Atencion Primaria y 816 sujetos con DMC. Resultados Un 21% de los sujetos contactados aleatorizados cumplieron criterios de DMC (edad media: 56 anos, 69% mujeres). La artrosis fue la causa mas frecuente de diagnostico de DMC. El 75% de los sujetos con DMC habia consultado a un medico, mayoritariamente de Atencion Primaria, y un 39% habia tomado tratamiento farmacologico en las 4 semanas anteriores a la encuesta. Un 38% considero que no debia molestar al medico con sus dolencias y el 29% que no se podia hacer nada para mejorar su estado de salud. El 49% obtenia informacion sobre su patologia/opciones terapeuticas a traves de fuentes no medicas, y solo el 24% la obtenia de su medico. El 91% de los medicos utilizaban antiinflamatorios no esteroideos (AINE) como farmacos de eleccion. El 42% de los pacientes en tratamiento tomaban un AINE de prescripcion (solo el 19% conocian sus efectos adversos). Conclusiones Aunque el presente estudio muestra una alta prevalencia del DMC en la poblacion espanola, el 25% de los sujetos nunca ha consultado a un medico. Ciertas actitudes y creencias de los sujetos que la padecen, asi como la falta de informacion y comunicacion entre medico y paciente pueden constituir no solo una barrera al diagnostico, sino tambien a la participacion activa del paciente en el manejo de su patologia.

SAT0331 Effect of Methotrexate on the Immnunogenicity of TNF Inhibitors in Spondyloartrhitis Patients

Background The spondyloarthritis (SpA) patients treated under TNF inhibitors (TNFi) with detectable antidrug antibodies (ADA) often develop loss of efficacy. Concomitant therapy with methotrexate (MTX) appears to reduce the the immunogenicity of biological drugs. Objectives To analyze if the use of combined therapy with MTX and TNFi can reduce the incidence of ADA and whether its effect is MTX dose dependent in SpA patients. Methods In this retrospective observational study, 162 SpA patients (including ankylosing spondylitis, Psoriatic SpA, SpA associated with inflammatory bowel disease and undifferentiated SpA) were included. The patients are treated with infliximab (Ifx) or adalimumab (Ada). The presence of ADA were measured at baseline and before each administration by ELISA to complete a follow up of 3 years. The patients were divided in two groups [MTX-15 (dose <15 mg/week) and MTX+15 (≥15 mg/week)] to study the influence of baseline MTX dose on immunogenicity. The statistical analysis was performed using SPSS 11.0. Results Eighty nine out of 162 (54,9%) patients were male. Eighty five out of 162 (52,5%) patients received Ifx and 77 out of 162 (47,5%) Ada. The mean duration of treatment was 13.38±9.19 years to Ifx and 12.71±10.46 years for Ada. Forty five patients received MTX weekly at baseline [25/85 (29.4%)in Ifx and 20/77 (26%)in Ada]. The mean dose of MTX was 15,9±4.76 mg/week. Twenty nine out of 162 (17,9%) patients developed ADA, and ADA presence was significantly higher in SpA patients on Ifx therapy [21/85 (24.7%) in Ifx vs 8/77 (10.4%) in Ada, p=0.018)]. The presence of ADA was less frequent in SpA patients taking MTX [3/162 (1.8%) with MTX vs 26/162 (16%) without MTX, p=0.021]. No statistically differences were observed in the influence of baseline MTX dose on the ADA appearance (in Ifx: 2/18 (11,1%) in MTX+15 vs 1/9 (11,1%)in MTX-15, p=1,0; in Ada: 1/17 (5,9%) in MTX+15 vs 0/4 (0,0%)in MTX-15, p=1,0). Conclusions In this cohort of SpA patients treated with Ifx and Ada, the use of MTX has a preventive effect on the ADA development. However, the baseline MTX dose is not a determinant factor to get this effect. Further prospective studies are needed to confirm these data. Disclosure of Interest A. Villalba Yllan: None declared, C. Plasencia Grant/research support: Pfizer, D. Pascual-Salcedo Grant/research support: Pfizer, Speakers bureau: Pfizer, D. Peiteado: None declared, L. Nuño: None declared, G. Bonilla: None declared, R. del Moral: None declared, A. Balsa Grant/research support: Pfizer, Speakers bureau: Pfizer, Roche, Abbvie, E. Martin Mola Speakers bureau: Pfizer, Roche, Abbvie, Amgen DOI 10.1136/annrheumdis-2014-eular.5819