Biologic therapy in severe and refractory peripheral ulcerative keratitis (PUK). Multicenter study of 34 patients.

PURPOSE: We assessed the efficacy and safety of biologic therapy in severe and refractory Peripheral Ulcerative Keratitis (PUK). DESIGN: Open-label multicenter study of biologic-treated patients with severe PUK refractory to conventional immunosuppressive drugs. SUBJECTS: We studied 34 patients (44 affected eyes) (24 women/10 men; mean age, 55.26±17.4 years). PUK was associated with a well-defined condition in 29 of them (rheumatoid arthritis [n = 20], psoriatic arthritis [n = 2], inflammatory bowel disease [n = 2], Behçet disease [n = 1], granulomatosis with polyangiitis [n = 1], microscopic polyangiitis [n = 1], systemic lupus erythematosus [n = 1] and axial spondyloarthritis [n = 1]). Besides topical and oral systemic glucocorticoids, patients had received: methylprednisolone pulses [n = 9], and conventional immunosuppressive drugs, mainly methotrexate [n = 18], and leflunomide [n = 7]. Eleven patients had required ocular surgery prior to biologic therapy. METHODS: Following biologic therapy, baseline main outcomes were compared with those found at 1st week, 1st and 6th months and 1st year. MAIN OUTCOME MEASURES: Efficacy and safety of biologic therapy. Efficacy was analyzed by the assessment of corneal inflammation (corneal thinning, central keratolysis and ocular perforation); other causes of ocular surface inflammation (scleritis, episcleritis); intraocular inflammation (uveitis); visual acuity and glucocorticoid sparing effect. RESULTS: The first biologic agents used were anti-TNFα drugs (n = 25); adalimumab (n = 16), infliximab (n = 8), etanercept (n = 1), and non-TNFα agents (n = 9); rituximab (n = 7), tocilizumab (n = 1) belimumab (n = 1) and abatacept (n = 1). During the follow-up, switching to a second biologic agent was required in 12 of the 25 (48%) patients treated with anti-TNFα drugs. However, no switching was required in those undergoing biologic therapy different from anti-TNFα agents. The main outcome variables showed a rapid and maintained improvement after a mean follow-up of 23.7 ± 20 months. Major adverse effects were tachyphylaxis, relapsing respiratory infections, supraventricular tachycardia, pulmonary tuberculosis and death, one each. CONCLUSIONS: Biologic therapy is effective and relatively safe in patients with severe and refractory PUK. Non-anti-TNFα agents appear to be effective in these patients.

Current status of multidisciplinary care in psoriatic arthritis in Spain: NEXUS 2.0 project. / Estado actual de la atención multidisciplinar para pacientes con artritis psoriásica en España: proyecto NEXUS 2.0.

OBJECTIVE: 1) To analyze the implementation of multidisciplinary care models in psoriatic arthritis (PsA) patients, 2) To define minimum and excellent standards of care. METHODS: A survey was sent to clinicians who already performed multidisciplinary care or were in the process of undertaking it, asking: 1) Type of multidisciplinary care model implemented; 2) Degree, priority and feasibility of the implementation of quality standards in the structure, process and result for care. In 6 regional meetings the results of the survey were presented and discussed, and the ultimate priority of quality standards for care was defined. At a nominal meeting group, 11 experts (rheumatologists and dermatologists) analyzed the results of the survey and the regional meetings. With this information, they defined which standards of care are currently considered as minimum and which are excellent. RESULTS: The simultaneous and parallel models of multidisciplinary care are those most widely implemented, but the implementation of quality standards is highly variable. In terms of structure it ranges from 22% to 74%, in those related to process from 17% to 54% and in the results from 2% to 28%. Of the 25 original quality standards for care, 9 were considered only minimum, 4 were excellent and 12 defined criteria for minimum level and others for excellence. CONCLUSIONS: The definition of minimum and excellent quality standards for care will help achieve the goal of multidisciplinary care for patients with PAs, which is the best healthcare possible.

Clinical, Patient-Reported, and Ultrasound Outcomes from an Open-Label, 12-week Observational Study of Certolizumab Pegol in Spanish Patients with Rheumatoid Arthritis with or without Prior Anti-TNF Exposure.

OBJECTIVES: To assess the effectiveness and safety of certolizumab pegol (CZP) in Spanish patients with RA. MATERIALS AND METHODS: SONAR (NCT01526434), a 12-week, open-label, prospective, observational, multicenter study. Patients with active RA for ≥3 months, according to ACR criteria, were treated with CZP (400mg at Weeks 0, 2 and 4, then 200mg every 2 weeks). The primary effectiveness endpoint was change from baseline (CFB) in Health Assessment Questionnaire-Disability Index (HAQ-DI) at Week 12. Other assessments included DAS28(ESR), patient's assessment of arthritis pain (PtAAP-VAS) and Short Form 36-item Health Survey (SF-36) physical component summary (PCS) and mental component summary (MCS). Joint inflammation was investigated using Power Doppler (PD) ultrasound (US), to detect effusion, synovial hypertrophy and synovial PD signal. PDUS outcomes assessed CFB to Week 12 in synovial hypertrophy, effusion and PD signal indices. RESULTS: A total of 77/80 enrolled patients received ≥1 dose of CZP. The 12-week mean reduction from baseline (SD) was -0.6 (0.6) for HAQ-DI and -2.2 (1.5) for DAS28(ESR). PtAAP-VAS was reduced from baseline (mean [SD]: -36.8 [26.8]) and improvements in SF-36 PCS and SF-36 MCS were reported. Synovial hypertrophy, effusion and PD signal indices were reduced from baseline to Week 12. One death was reported during the study. CONCLUSIONS: Spanish patients with RA demonstrated improvements in clinical, PDUS and patient-reported outcomes over 12 weeks of CZP treatment. No new safety signals were identified, and the safety profile was in line with previous CZP studies. These results support previous clinical trial findings investigating CZP treatment for active RA.

Clinical and therapeutic management of rheumatoid arthritis with biological disease-modifying antirheumatic drugs: RADAR study.

To describe the clinical and therapeutic management of rheumatoid arthritis (RA) patients with biological disease-modifying antirheumatic drugs (bDMARDs), alone or in combination with conventional synthetic DMARDs (csDMARDs), as well as analysing changes over time in bDMARD use. An observational, retrospective, multicentre study was conducted in the rheumatology departments of 10 public Spanish hospitals. Patients with RA treated with bDMARDs at baseline who had medical records available in the data collection period 2013-2016 were included. All visits to rheumatology departments recording any type of bDMARD modification (dose, etc.) were collected. Clinical characteristics, concomitant treatment, resource use, work productivity and quality of life (QoL) were recorded. 128 patients were included: 81 received first-line bDMARD treatment, 28 second-line bDMARD treatment and 19 received third or later lines. Mean study follow-up was 4.1 years. Assessment of DAS28 was available in 54.6% of visits. At baseline, 48.7% of patients had moderate-high disease activity. At final observation, 69.5% of patients continued with the first bDMARD. Tumour necrosis factor blockers were administered to 85.2% of patients in first line, 45.7% in second line and 18.1% in third or later lines. At final observation, 80.2% of patients still felt pain/discomfort. As expected, those with higher disease activity had higher loss of work productivity and lower QoL, as assessed by DAS28, than patients with lower disease activity. Drugs represented 82.6% of the total cost. In this Spanish cohort of 128 patients, most patients remained on the first prescribed bDMARD, despite remaining signs and symptoms.

Successful Optimization of Adalimumab Therapy in Refractory Uveitis Due to Behçet's Disease.

PURPOSE: To assess efficacy, safety, and cost-effectiveness of adalimumab (ADA) therapy optimization in a large series of patients with uveitis due to Behçet disease (BD) who achieved remission after the use of this biologic agent. DESIGN: Open-label multicenter study of ADA-treated patients with BD uveitis refractory to conventional immunosuppressants. SUBJECTS: Sixty-five of 74 patients with uveitis due to BD, who achieved remission after a median ADA duration of 6 (range, 3-12) months. ADA was optimized in 23 (35.4%) of them. This biologic agent was maintained at a dose of 40 mg/subcutaneously/2 weeks in the remaining 42 patients. METHODS: After remission, based on a shared decision between the patient and the treating physician, ADA was optimized. When agreement between patient and physician was reached, optimization was performed by prolonging the ADA dosing interval progressively. Comparison between optimized and nonoptimized patients was performed. MAIN OUTCOME MEASURES: Efficacy, safety, and cost-effectiveness in optimized and nonoptimized groups. To determine efficacy, intraocular inflammation (anterior chamber cells, vitritis, and retinal vasculitis), macular thickness, visual acuity, and the sparing effect of glucocorticoids were assessed. RESULTS: No demographic or ocular differences were found at the time of ADA onset between the optimized and the nonoptimized groups. Most ocular outcomes were similar after a mean ± standard deviation follow-up of 34.7±13.3 and 26±21.3 months in the optimized and nonoptimized groups, respectively. However, relevant adverse effects were only seen in the nonoptimized group (lymphoma, pneumonia, severe local reaction at the injection site, and bacteremia by Escherichia coli, 1 each). Moreover, the mean ADA treatment costs were lower in the optimized group than in the nonoptimized group (6101.25 euros/patient/year vs. 12 339.48; P < 0.01). CONCLUSION: ADA optimization in BD uveitis refractory to conventional therapy is effective, safe, and cost-effective.