Letter to the editor

Exacerbation of combined pulmonary fibrosis and emphysema syndrome during tocilizumab therapy for rheumatoid arthritis

Elaborar unas recomendaciones multidisciplinares para mejorar el manejo de la enfermedad pulmonar intersticial difusa asociada a la artritis reumatoide (EPID-AR).

Un panel de reumatólogos y neumólogos expertos identificó preguntas clínicas de investigación relevantes para el objetivo del documento. Se realizaron revisiones sistemáticas de la evidencia, que se graduó de acuerdo con los criterios del SIGN. Tras ello, se formularon las recomendaciones.

Se seleccionaron seis preguntas PICO, tres de las cuales específicamente evaluaron la seguridad y la eficacia de los glucocorticoides, fármacos de acción lenta moduladores de la enfermedad (FAME) sintéticos clásicos e inmunosupresores, FAME biológicos, FAME sintéticos dirigidos y antifibróticos en el tratamiento de los pacientes con EPID-AR. Se formularon un total de 12 recomendaciones específicas sobre este tema con base en la evidencia encontrada y/o consenso de expertos.

Se presenta el primer documento oficial SER-SEPAR de recomendaciones específicas para el abordaje terapéutico de la EPID-AR con el fin de ayudar en la toma de decisiones a los clínicos directamente implicados en su manejo.

To develop multidisciplinary recommendations to improve the management of rheumatoid arthritis-related interstitial lung disease (RA-ILD).

Clinical research questions relevant to the objective of the document were identified by a panel of rheumatologists and pneumologists selected based on their experience in the field. Systematic reviews of the available evidence were conducted, and evidence was graded according to the Scottish Intercollegiate Guidelines Network (SIGN) criteria. Specific recommendations were made.

Six PICO questions were selected, three of which analysed the safety and effectiveness of glucocorticoids, classical synthetic disease-modifying anti-rheumatic drugs (DMARDs) and other immunosuppressants, biological agents, targeted synthetic DMARDs, and antifibrotic therapies in the treatment of this complication. A total specific of 12 recommendations on this topic were formulated based on the evidence found and/or expert consensus.

We present the first official SER-SEPAR document with specific recommendations for RA-ILD management developed to resolve some common clinical questions, reduce clinical healthcare variability, and facilitate decision-making for patients.

The prevalence of classifiable and unclassifiable causes of lung fibrosis and its implications for survival are mostly unknown in combined pulmonary fibrosis and emphysema (CPFE).

Patients with >10% involvement of both emphysema and lung fibrosis seen over 11 years at our institution were reviewed independently by expert radiologists for fibrotic and emphysematous findings and overall fibrotic CT pattern. Underlying interstitial lung disease (ILD) diagnoses and baseline demographic and clinical characteristics were collated and assessed for predictors of comparative survival.

In this retrospective cohort, 179 CPFE patients were identified and categorized as 58 usual interstitial pneumonia/idiopathic pulmonary fibrosis (UIP/IPF) (32%), 42 secondary ILD (23%), and 79 unclassifiable ILD (44%). The most prevalent (47%) radiologic pattern was ‘unclassifiable’, followed by ‘consistent’ and ‘possible’ UIP pattern in 38%. Adjusted predictors of mortality for the cohort as a whole included age (HR 1.03[1.01–1.06], P = 0.002), percent predicted diffusing capacity for carbon monoxide (unit HR 0.97 [0.96–0.99], P = 0.001), honeycombing (HR 1.58 [1.02–2.43], P = 0.04), and right ventricular dysfunction (HR 2.28 [1.39–3.97], P = 0.002). Survival was similar between CPFE with secondary ILD and CPFE with UIP/IPF, while CPFE with unclassifiable ILD had better comparative survival (Log rank = 0.026).

Our findings suggest only about a third of CPFE patients represent suspected UIP/IPF; the majority were clinically and radiologically unclassifiable ILD whose survival was comparatively better. Identifiable or secondary causes of lung fibrosis in CPFE occurred in about a fifth of presenting patients.

Interstitial lung disease (ILD) is one of the most serious complications of rheumatoid arthritis (RA). In the present study, we aimed to assess the efficacy of abatacept (ABA) in patients with ILD associated to RA.

National multicenter, non-controlled, open-label registry study of RA patients with ILD treated with ABA.

63 patients (36 women) with RA-associated ILD undergoing ABA therapy were studied. The mean ± standard deviation age at the time of the study was 63.2 ± 9.8 years. The median duration of RA and ILD from diagnosis were 6.8 and 1 year, respectively. RA was seropositive in 55 patients (87.3%). In 15 (23.8%) of 63 patients the development of ILD was closely related to the administration of synthetic or biologic disease modifying anti-rheumatic drugs. After a follow-up of 9.4 ± 3.2 months, two-thirds of patients remained stable whereas one-quarter experienced improvement in the Modified Medical Research Council scale. At that time forced vital capacity remained stable in almost two-thirds of patents and improved in one out of five patients assessed. Also, diffusing capacity of the lung for carbon monoxide remained stable in almost two-thirds and showed improvement in a quarter of the patients assessed. At 12 months, 50% of the 22 patients in whom chest HRCT scan was performed due persistence of respiratory symptoms showed stabilization, 8 (36.4%) improvement and 3 worsening of the HRCT scan pattern. Eleven of 63 patients had to discontinue ABA, mainly due to adverse events.

ABA appears to be an effective in RA-associated ILD.

This chapter describes the involvement of the lung in systemic inflammatory joint disease (IJD) with a particular focus on rheumatoid arthritis, although the topics of pulmonary involvement in ankylosing spondylitis and psoriatic arthritis are also addressed. Interstitial lung disease is the most lethal pulmonary complication of IJD and the chapter describes recent advances in both our understanding of this complication and the therapeutic options that offer real hope for improved outcomes. Although less well recognised, airways disease is just as common and its association with IJD is described in some detail, with a section devoted to the recent surge in interest in bronchiectasis. Acute pulmonary infection is common in IJD and its management is reviewed in some detail. Although pleural disease is less common than it once was, its treatment is explored. We conclude by reviewing the relationship between the drug therapies employed in IJD and their effects on the lung.

Generar recomendaciones sobre el bloqueo de la interleucina 6 (IL-6) en pacientes con artritis reumatoide (AR), basadas en la mejor evidencia y experiencia.

Se seleccionó a 10 expertos reumatólogos en el manejo de los inhibidores de la IL-6. Los 2 coordinadores generaron 23 preguntas sobre el bloqueo de la IL-6 en la AR (perfiles de indicación, eficacia, seguridad, etc.) para ser contestadas mediante una revisión sistemática de la literatura. Con base en las preguntas se definieron los criterios de inclusión y exclusión, y las estrategias de búsqueda (para interrogar Medline, Embase y la Cochrane Library). Dos revisores seleccionaron los artículos resultantes de la búsqueda. Se generaron tablas de evidencia. Paralelamente, se evaluaron abstracts de congresos de EULAR y ACR. Con toda esta evidencia los coordinadores propusieron 8 recomendaciones preliminares que se evaluaron, discutieron y votaron en una reunión de grupo nominal con el resto de los expertos. Para cada recomendación se estableció el nivel de evidencia y grado de recomendación, y el grado de acuerdo mediante un Delphi. Se definió acuerdo si al menos el 80% de los participantes contestaban sí a la recomendación (sí o no).

Las 8 recomendaciones preliminares se aceptaron tras el Delphi. Abarcan aspectos como su uso en monoterapia, en combinación, en pacientes refractarios o intolerantes, la evaluación de su respuesta, la optimización o la gestión del riesgo.

Este documento pretende resolver algunos interrogantes clínicos habituales y facilitar la toma de decisiones con el bloqueo de la IL-6 en el manejo de la AR.

To draft recommendations on interleukin 6 (IL-6) blockade in rheumatoid arthritis (RA), based on best evidence and experience.

A group of 10 experts on IL-6 blockade in RA was selected. The 2 coordinators formulated 23 questions about IL-6 blockade (indications, efficacy, safety, etc.). A systematic review was conducted to answer the questions. Using this information, inclusion and exclusion criteria were established, as were the search strategies (Medline, EMBASE and the Cochrane Library were searched). Two different reviewers selected the articles. Evidence tables were created. At the same time, European League Against Rheumatism and American College of Rheumatology abstracts were evaluated. Based on this evidence, the coordinators proposed preliminary recommendations that the experts discussed and voted on in a nominal group meeting. The level of evidence and grade of recommendation were established using the Oxford Centre for Evidence Based Medicine and the level of agreement with the Delphi technique (2 rounds). Agreement was established if at least 80% of the experts voted yes (yes/no).

The 8 preliminary recommendations were accepted after the Delphi process. They covered aspects such as the use of these therapies in monotherapy, in combination, in patients with refractory disease or intolerant patients, response evaluation, optimization and risk management.

The manuscript aims to solve frequently asked questions and aid in decision making strategies when treating RA patients with IL-6 blockade.

La artritis reumatoide (AR) es una enfermedad sistémica que en las últimas décadas ha tenido múltiples opciones terapéuticas. Con la información disponible en la literatura no se recomienda el uso de terapia biológica en pacientes con enfermedad pulmonar difusa, dado que estos medicamentos pueden exacerbar el compromiso pulmonar. Un medicamento de más reciente aparición es el inhibidor de la enzima Janus quinasa, el cual es una opción terapéutica en monoterapia o combinado para pacientes con AR en moderada y alta actividad de la enfermedad, con contraindicación al uso de FARME sintéticos o biológicos, y en pacientes con fallo terapéutico, no obstante, su seguridad a nivel pulmonar no ha sido evaluada en ensayos clínicos y la información disponible es escasa. Describimos el tratamiento, seguimiento y resultados del uso de tofacitinib en 4 pacientes con enfermedad pulmonar secundaria a AR en una serie de casos.

Rheumatoid arthritis (RA) is a systemic disease that, in the last decades, has had multiple therapeutic options. With the information available in the literature, the use of biological therapy in patients with diffuse pulmonary disease is not recommended, given that these medications can exacerbate lung involvement. A newer drug is the inhibitor of the enzyme Janus kinase, which is an option in the single or combined therapy or combined for patients with RA of moderate and high activity of the disease with contraindication to the use of synthetic or biological DMARDs and in patients with therapeutic failure. However, its safety at the pulmonary level has not been evaluated in clinical trials and the available information is scarce. A description is presented of the treatment, follow-up, and results of the use of tofacitinib in a series of four patients with pulmonary disease secondary to RA.