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Background With the expanding use of Biological Agents (BA), in particular TNF inhibitors, opportunistic infections (OI) are a major concern in Rheumatology. Objectives a) To describe the incidence of OI global and by periods in Rheumatoid Arthritis (RA). b) To compare the risk of OI by BA. Methods We performed a retrospective longitudinal observational study from 1/1/2000 to 23/11/2013. We included subjects followed up in our outpatient clinic, diagnosed with RA according to ACR criteria 87, whom started treatment with a BA [etanercept (ETN), golimumab (GOLI), certolizumab (CTZ), infliximab (IFX), adalimumab (ADA), rituximab (RTX), abatacept (ABA), or tozilizumab (TZL)]. Our primary end point was OI that involved the suspension of the BA. We consider OI when there was a positive culture (for Candida, Aspergillus or Herpes) or compatible symptoms that responded to specific treatment. We also collected secondary variables: sociodemographic (age, sex); clinical (disease duration, types of BA, hospital admission, previous BA). Statistical analysis: We used survival techniques to estimate the incidence of global OI and OI by periods (1st: 98-2002, 2nd:2002-2007, 3rd: 2007-2013), expressed per 1000 patient-year [CI 95%]. The exposure time was defined from the start date of each BA to suspension, loss of follow up or end of study (23/11/2013). We performed Cox regression models (adjusted by age, duration of RA, sex, calendar time and prior BA) to compare the risk of OI between each BA. Results 405 RA patients were included in the study, they started 744 different courses of BA treatment, with a total follow-up of 1,612 patient-years. Of these, 81% were women with a mean age at diagnosis of 52.5±13 years. The most frequently used drug was ADA (32%), followed by ETN (25%), IFX (21%) and RTX (14%). There were 16 OI (6 Candidas, 2 Aspergillus and 8 Herpes Zoster), 40% required hospitalization and two died of disseminated candidiasis. The incidence of OI was 9.9 [6.1-16.2], and tended to increase over time (1st: 5.9 [1.5 to 23.9]; 2nd: 7.7 [2.9 to 20, 6]; and 3rd: 13.1 [7.1 to 24.3]). We only registered OI cases in anti-TNF and RTX, which is the drug with higher incidence (n=3, I: 20.1 [6.4 to 62.4]). We found no statistically significant association between RTX compared with other BA and the development of OI Conclusions The incidence of OI and its evolution over time in real life conditions is described. It seems that OI tend to increase over time and we had two cases with fatal outcome. Doctors using BA should be concerned about this problem and be aware of the optimal methods for the detection and management of OI. We did not find statistical differences in the rate of OI between BA. Disclosure of Interest : None declared DOI 10.1136/annrheumdis-2014-eular.4509

Background:There is a well-known risk of developing adverse drug reactions (ADR) in rheumatology due, mainly, to the Disease Modifying Antirheumatic Drugs (DMARD) used. There is no doubt about their efficacy in Rheumatoid Arthritis (RA), but it is necessary to increase our knowledge of their ADR, especially those that lead to discontinuationObjectives:To describe the incidence and characteristics of ADR related with DMARD in patients with incident RA as well as the factors involved in their developmentMethods:Observational retrospective longitudinal study between April 15th 2007 and December 31st 2016. Inclusion criteria: patients diagnosed with RA between April 15th 2007 and June 31st 2011 followed until December 31st 2016 whom started any DMARD. Primary endpoint: development of an ADR that required discontinuation of the DMARD (moderate: discontinuation; severe: discontinuation with hospitalization or death). Co-variables: sociodemographic; clinical and therapy. Statistical analysis: incidence rates of discontinuation (IR) per 100 patient-years were estimated using survival techniques with their respective 95% confidence interval [CI]. Comparisons between associated factors were run by Cox bivariate and multivariate regression models. Results were expressed by hazard ratio (HR) and [CI]Results:We included 1054 courses of DMARD treatment in 405 patients (2277.9 patient-years). 78.3% were women with a mean age at diagnosis of 57±15 years. During follow-up, 16.3% of patients were taking biological DMARD, 73.3% were using monotherapy and 89% were taking corticoids. There were 369 ADR in 212 patients, 88.9% moderate. Gastrointestinal was the most frequent cause of ADR (26.3%), followed by infections (12.2%). IR are shown in table 1 and the multivariate analysis in table 2. Regarding type of DMARD, Abatacept had the highest risk of ADR development (HR:4.9[2.1–11.2]) compared to the other drugs followed by Gold (HR:1.6[1–2.6]) and Leflunomide (HR:1.4[1.1–1.9]). Methotrexate was the safest drug compared with the others (0.6[0.5–0.8])Table 1GlobalWomenMen2277.91835.4442.53692967316.216.116.514.6–17.914.4–18.113.1–20.7 By therapy regimenMonotherapyDouble therapyTriple therapy 1609.5568.999.4 20013237 12.423.237.2 10.8–14.319.6–27.526.9–51.4By type of DMARDSyntheticBiological 2048.3229.5 32643 15.918.7 14.3–17.713.9–25.3By drugAbataceptAdalimumabAntimalarialsAzathioprineCertolizumabEtanerceptGolimumabInfliximabLeflunomideMethotrexateGoldRituximabSulfasalazine 8.381.5749.7191665.29.118.4340.41463.583.626.3154 5101573412568520633145 60.612.320.915.724.818.454.932.72514.139.53.829.2 25.2–145.56.6–22.817.9–24.55.1–48.89.3–66.210.5–32.422.9–131.914.7–72.720.2–30.912.3–16.128–55.50.5–2721.8–39.1Table 2MonotherapyDouble therapyTriple therapy12 4.2-1.5–2.52.6–6.8-0 0 Congestive heart failure1.81.2–2.70.002Liver disease21.2–3.30.012Conclusions:The IR of ADRwas 16.2%, being similar in all age categories. Gastrointestinal was the main cause of ADR followed by infections. We have found differences in discontinuation rates among DMARD ...

BackgroundHaving demonstrated the safety and efficacy of Methotrexate (MTX) in the treatment of Giant Cell Arteritis (GCA), it is important to know the long-term survival of the drug in these patients.ObjectivesTo describe the incidence of discontinuation of MTX and its causes in a cohort of patients with GCA.MethodsRetrospective longitudinal observational study of 22 years of follow-up. Subjects: Patients treated in the Department of Rheumatology of the Hospital Clínico San Carlos, Madrid, from January 1991 until September 2014, diagnosed (according to ICD 10) ACG and treated with MTX. Primary endpoint: discontinuation of MTX due to: inefficiency; adverse event (AE) (moderate: discontinuation of the drug regardless the impact; severe: discontinuation and hospitalization or death); patient choice; improvement or remission; and other decisions of the physician. Secondary endpoints: a) sociodemographic (age, sex); b) clinical: baseline comorbidity; c) erythrocyte sedimentation rate; d) characteristics of the arteritis outbreak; e) cumulative dose of corticosteroids during the first 3 months. Statistical analysis: Description of sociodemographic and clinical characteristics of patients included and of discontinuation causes, through frequency distribution, and mean and standard deviation or median and percentiles. To estimate MTX discontinuation rates, survival techniques were used, incidence is expressed per 100 patients * year with their respective 95% confidence interval (95% CI).ResultsEighty two GCA patients were included in the study, the same received 96 courses of treatment, with a total follow-up of 168.3 patient * year. From these patients, 75.61% were women with a mean age at diagnosis of 76.7±7.3 years. At diagnosis, 58.5% of patients were hypertensive, and 22% diabetics. Temporal artery biopsy was performed in 92% of patients and it was positive in 72%. The mean sedimentation rate was 84.6±28.1 mm/h and the cumulative dose of corticosteroids in the first 3 months was 32.3±11.8 mgr. The most common clinical was headache (87%), abnormal temporal artery (46%), jaw claudication (44%), associated polymyalgia rheumatica (PMR) (42%), and asthenia (40%). Sixty three discontinuations (65%) were recorded: 57% by AE (infections were the most common cause (58%); 32% due to improvement or remission; 5% due to inefficiency; 3% due to patient decision and 3% due to decision of the physician. In 9.3% of patients, follow-up was lost and 3 patients died (one related to taking MTX). MTX survival in the first year was 70%, 50% in the second year and it was 18% at year 5. The incidence of suspension of MTX was 37.4 (95% CI 29.2 to 47.9), with an incidence of 34.9 (95% CI 26.3 to 46.3) in women and 48.5 (IC 95% CI 29.2 to 80.4) in men. If we stratify patients into three categories (<75 years, 75-85 years and>85 years), the incidence of discontinuation increases with age. In the table, MTX discontinuation rates are shown by cause.ConclusionsDiscontinuation rate estimated in our cohort is of 37% patients * year, being the most ...

BackgroundClinical trials show the efficacy of Methotrexate (MTX) in giant cell arteritis (GCA). It is necessary to corroborate these results in real life.ObjectivesTo assess the incidence and the risk of ischaemic relapses in GCA patients treated with and without Methotrexate (MTX) in clinical practice.MethodsRetrospective longitudinal observational study. Subjects: patients treated at the Rheumatology Service of the Hospital Clínico San Carlos with the diagnosis of GCA. They were included from the date of diagnosis (January 1991 to September 2013) and followed-up until lost of follow up or Sept-2014. Main outcome: relapses by isquemic event (RIE): Presence of mandibular claudication, visual manifestations (blurred vision, diplopia, transient or permanent loss of vision), cerebrovascular accident, ischaemic heart disease or claudication of limbs, after having achieved an objective improvement, associated with an increase in the erythrocyte sedimentation rate (ESR) and the need to increase corticosteroids (at least 10 mg over the previous dose). Independent variable: exposure to MTX over time. Secondary variables: sociodemographic, clinical and treatment. Statistical analysis: RIE rates were assessed by survival techniques, expressing the incidence per 100 patients*year with their 95% confidence interval [CI]. The influence of MTX on the REI was analysed by multivariate Cox regression models. Results were expressed as Hazard ratios (HR) with their respective CI.Results168 patients were included with a follow-up of 675.59 patients*year. 80.36% were women (mean age: 76.77±7 years). The most prevalent comorbidities were arterial hypertension (64%), dyslipidemia (34%), cardiovascular pathology (30%) and polymyalgia rheumatica (13.77%). The most common clinical symptom at diagnosis was headache (87.43%), systemic involvement (55%) and polymyalgia rheumatica (49.70%). The ESR was 78±30.85 mmHg and Hb of 12.06±1.58 mg/dL. 46.39% had a positive biopsy. 64% were on MTX (mean dose: 10 mg) at any time during the follow-up, from those 68% started MTX in the first 4 weeks after diagnosis. The mean dose of corticosteroids was 50.72±15.46 mg. There were 21 relapses by ischaemic events (12.5%), with an incidence of 3.1 [2.02–4.77]. The median time to first RIE was 0.4 [p25–75: 0.4–5.1] years. The incidence of RIE in patients exposed to MTX was 1.92 [0.8–4.62], whereas in those without MTX was 3.84 [2.36–6.28]. The incidence of REI in women was 3.44 [2.17–5.46] and in men was 1.97 [0.6–6]. In the multivariate analysis after adjusting for age, sex, disease activity and calendar time, exposure to MTX had less risk of relapse by ischaemic event compared to those without MTX (HR 0.3 [0.096–0.99]; p=0.048).ConclusionsThe frequency of REI was 12.5%. The incidence of REI was 3% patients-year. With the results observed in this study, the use of MTX seems to decrease the risk of relapses by ischaemic event.Disclosure of InterestNone declared