Adalimumab plus Methotrexate for Uveitis in Juvenile Idiopathic Arthritis

Estándar

Athimalaipet V. Ramanan, F.R.C.P.C.H.,

BACKGROUND

Adalimumab, a fully human anti–tumor necrosis factor α monoclonal antibody, is effective in the treatment of juvenile idiopathic arthritis (JIA). We tested the efficacy of adalimumab in the treatment of JIA-associated uveitis.

METHODS

In this multicenter, double-blind, randomized, placebo-controlled trial, we assessed the efficacy and safety of adalimumab in children and adolescents 2 years of age or older who had active JIA-associated uveitis. Patients who were taking a stable dose of methotrexate were randomly assigned in a 2:1 ratio to receive either adalimumab (at a dose of 20 mg or 40 mg, according to body weight) or placebo, administered subcutaneously every 2 weeks. Patients continued the trial regimen until treatment failure or until 18 months had elapsed. They were followed for up to 2 years after randomization. The primary end point was the time to treatment failure, defined according to a multicomponent intraocular inflammation score that was based on the Standardization of Uveitis Nomenclature criteria.

RESULTS

The prespecified stopping criteria were met after the enrollment of 90 of 114 patients. We observed 16 treatment failures in 60 patients (27%) in the adalimumab group versus 18 treatment failures in 30 patients (60%) in the placebo group (hazard ratio, 0.25; 95% confidence interval [CI], 0.12 to 0.49; P<0.0001 [the prespecified stopping boundary]). Adverse events were reported more frequently in patients receiving adalimumab than in those receiving placebo (10.07 events per patient-year [95% CI, 9.26 to 10.89] vs. 6.51 events per patient-year [95% CI, 5.26 to 7.77]), as were serious adverse events (0.29 events per patient-year [95% CI, 0.15 to 0.43] vs. 0.19 events per patient-year [95% CI, 0.00 to 0.40]).

CONCLUSIONS

Adalimumab therapy controlled inflammation and was associated with a lower rate of treatment failure than placebo among children and adolescents with active JIA-associated uveitis who were taking a stable dose of methotrexate. Patients who received adalimumab had a much higher incidence of adverse events and serious adverse events than those who received placebo. (Funded by the NIHR Health Technology Assessment Programme and Arthritis Research UK; SYCAMORE EudraCT number, 2010-021141-41.)

http://www.nejm.org/doi/full/10.1056/NEJMoa1614160?query=TOC

2016 updated EULAR evidence-based recommendations for the management of gout

Estándar

P. Richette

Abstract

Background New drugs and new evidence concerning the use of established treatments have become available since the publication of the first European League Against Rheumatism (EULAR) recommendations for the management of gout, in 2006. This situation has prompted a systematic review and update of the 2006 recommendations.

Methods The EULAR task force consisted of 15 rheumatologists, 1 radiologist, 2 general practitioners, 1 research fellow, 2 patients and 3 experts in epidemiology/methodology from 12 European countries. A systematic review of the literature concerning all aspects of gout treatments was performed. Subsequently, recommendations were formulated by use of a Delphi consensus approach.

Results Three overarching principles and 11 key recommendations were generated. For the treatment of flare, colchicine, non-steroidal anti-inflammatory drugs (NSAIDs), oral or intra-articular steroids or a combination are recommended. In patients with frequent flare and contraindications to colchicine, NSAIDs and corticosteroids, an interleukin-1 blocker should be considered. In addition to education and a non-pharmacological management approach, urate-lowering therapy (ULT) should be considered from the first presentation of the disease, and serum uric acid (SUA) levels should be maintained at<6 mg/dL (360 µmol/L) and <5 mg/dL (300 µmol/L) in those with severe gout. Allopurinol is recommended as first-line ULT and its dosage should be adjusted according to renal function. If the SUA target cannot be achieved with allopurinol, then febuxostat, a uricosuric or combining a xanthine oxidase inhibitor with a uricosuric should be considered. For patients with refractory gout, pegloticase is recommended.

Conclusions These recommendations aim to inform physicians and patients about the non-pharmacological and pharmacological treatments for gout and to provide the best strategies to achieve the predefined urate target to cure the disease.

http://dx.doi.org/10.1136/annrheumdis-2016-209707

EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2016 update

Estándar

J. Smolen et al.

Abstract

Recent insights in rheumatoid arthritis (RA) necessitated updating the European League Against Rheumatism (EULAR) RA management recommendations. A large international Task Force based decisions on evidence from 3 systematic literature reviews, developing 4 overarching principles and 12 recommendations (vs 3 and 14, respectively, in 2013). The recommendations address conventional synthetic (cs) disease-modifying antirheumatic drugs (DMARDs) (methotrexate (MTX), leflunomide, sulfasalazine); glucocorticoids (GC); biological (b) DMARDs (tumour necrosis factor (TNF)-inhibitors (adalimumab, certolizumab pegol, etanercept, golimumab, infliximab), abatacept, rituximab, tocilizumab, clazakizumab, sarilumab and sirukumab and biosimilar (bs) DMARDs) and targeted synthetic (ts) DMARDs (Janus kinase (Jak) inhibitors tofacitinib, baricitinib). Monotherapy, combination therapy, treatment strategies (treat-to-target) and the targets of sustained clinical remission (as defined by the American College of Rheumatology-(ACR)-EULAR Boolean or index criteria) or low disease activity are discussed. Cost aspects were taken into consideration. As first strategy, the Task Force recommends MTX (rapid escalation to 25 mg/week) plus short-term GC, aiming at >50% improvement within 3 and target attainment within 6 months. If this fails stratification is recommended. Without unfavourable prognostic markers, switching to—or adding—another csDMARDs (plus short-term GC) is suggested. In the presence of unfavourable prognostic markers (autoantibodies, high disease activity, early erosions, failure of 2 csDMARDs), any bDMARD (current practice) or Jak-inhibitor should be added to the csDMARD. If this fails, any other bDMARD or tsDMARD is recommended. If a patient is in sustained remission, bDMARDs can be tapered. For each recommendation, levels of evidence and Task Force agreement are provided, both mostly very high. These recommendations intend informing rheumatologists, patients, national rheumatology societies, hospital officials, social security agencies and regulators about EULAR’s most recent consensus on the management of RA, aimed at attaining best outcomes with current therapies.

http://dx.doi.org/10.1136/annrheumdis-2016-210715

2016 update of the EULAR recommendations for the management of early arthritis

Estándar

B. Combe et al.

Abstract

Objectives Since the 2007 recommendations for the management of early arthritis have been presented, considerable research has been published in the field of early arthritis, mandating an update of the 2007 European League Against Rheumatism (EULAR) recommendations for management of early arthritis.

Methods In accordance with the 2014 EULAR Standardised Operating Procedures, the expert committee pursued an approach that was based on evidence in the literature and on expert opinion. The committee involved 20 rheumatologists, 2 patients and 1 healthcare professional representing 12 European countries. The group defined the focus of the expert committee and target population, formulated a definition of ‘management’ and selected the research questions. A systematic literature research (SLR) was performed by two fellows with the help of a skilled librarian. A set of draft recommendations was proposed on the basis of the research questions and the results of the SLR. For each recommendation, the categories of evidence were identified, the strength of recommendations was derived and the level of agreement was determined through a voting process.

Results The updated recommendations comprise 3 overarching principles and 12 recommendations for managing early arthritis. The selected statements involve the recognition of arthritis, referral, diagnosis, prognostication, treatment (information, education, pharmacological and non-pharmacological interventions), monitoring and strategy. Eighteen items were identified as relevant for future research.

Conclusions These recommendations provide rheumatologists, general practitioners, healthcare professionals, patients and other stakeholders with an updated EULAR consensus on the entire management of early arthritis.

http://dx.doi.org/10.1136/annrheumdis-2016-210602

Metotrexato. ¿Cuáles son los Efectos Secundarios del Metotrexato más frecuentes?

Estándar

 

Como ya hemos mencionado en diversas ocasiones, los efectos secundarios que pueden aparecer con la toma de Metotrexato (MTX) son en su mayoría leves, aunque eso no obsta para que en un determinado grupo de pacientes haya que suspenderlo. Por lo tanto, una cosa es la gravedad y otra las molestias derivadas de su uso, que algunos pacientes no pueden (o no desean) sobrellevar.

Las molestias más frecuentes con la toma de MTX son: falta de apetito, nauseas y/o vómitos, ‘dolor de estómago’ y diarrea. En absoluto tienen que aparecer todos a la vez, ya que hay pacientes que solo tienen nauseas, otros diarreas y otros, finalmente, un agrupamiento de los síntomas mencionados. En otros casos el paciente refiere mareos, dolor de cabeza o alteración del estado de ánimo

Con menor frecuencia pueden aparecer: aftas bucales o (mucho menos frecuente) úlceras en estómago o en el intestino.

Hay pacientes que notan caída fácil del cabello (pero prácticamente nunca, hasta llegar al punto de la alopecia que ocurre con la quimioterapia)

Otros pacientes cuentan que el día de la toma del MTX y el día siguiente se encuentran ‘mal’, están cansados, sin ganas de hacer nada

¿Se pueden corregir estas molestias?

La respuesta es SI. La toma de ácido fólico al día siguiente (que todos los pacientes toman) mitiga en muchos pacientes la aparición de estas molestias. En personas con los síntomas descritos arriba, muchas veces incrementar la dosis de ácido fólico suele ser suficiente para aliviar los síntomas. Otras veces es necesario añadir otros fármacos para aliviar las molestias.

Como dijimos arriba, estos efectos secundarios se consideran ‘leves’, en el sentido de que no comprometen en absoluto el futuro del paciente. Pero hay que reconocer que a veces son tan intensos que no queda más remedio que suspender el fármaco. No obstante lo comentado, solo en pocos pacientes hay que llegar a este extremo.

¿Y el hígado?…en el próximo post…hablaremos de ello…