Abstract
IntroductionInterstitial lung disease (ILD) is a common extra-articular condition in rheumatoid arthritis (RA), but few studies have systematically investigated its incidence and risk factors in patients receiving anti-tumor necrosis factor-alpha (anti-TNFα) agents or alternate mechanisms of action (MOAs) (e.g., T-cell, B-cell, and interleukin-6 inhibitors).MethodsRA patients at least 18 years old were selected from the MarketScan databases (2010–2012) if they had at least one prescription/administration of abatacept, rituximab, tocilizumab, or anti-TNF after having discontinued a different biologic agent and meeting enrollment criteria. Cox models estimated the risk of incident ILD and ILD-related hospitalization. Sensitivity analyses used an alternate ILD case definition.ResultsWe identified 13,795 episodes of biologic exposure in 11,219 patients. Mean (standard deviation) follow-up was 0.7 (0.5) years. Patients receiving alternate MOA agents were more likely to have had recent exposure to steroids, prior exposure to a greater number of biologics, and history of ILD, anemia, chronic obstructive pulmonary disease, and other pulmonary conditions. When the sensitive definition was used, unadjusted ILD incidence rates (95 % confidence interval, or CI) ranged from 4.0 (1.6–8.2, abatacept) to 12.2 (5.6–23.2, infliximab) per 1000 person-years. Being older (hazard ratio (HR) 3.5; 95 % CI 2.1–6.0), being male (HR 3.1; 95 % CI 1.2–8.4), and having another pulmonary condition (HR 4.8; 95 % CI 1.7–13.7) were associated with increased ILD incidence in either sensitive and/or specific models. There were no significant differences by biologic class. Hospitalization rates (95 % CI) when the sensitive definition was used ranged from 55.6 (6.7–200.7, tocilizumab) to 262.5 (71.5–672.2, infliximab). In Cox models, recent methotrexate exposure was associated with reduced ILD hospitalization (HR 0.16; 95 % CI 0.06–0.46), whereas being male (HR 2.5; 95 % CI 1.3–4.8) and having had a hospitalization for asthma (HR 3.4; 95 % CI 1.2–9.8) or ILD/pneumonia (HR 2.3; 95 % CI 1.1–4.7) in the 12 months prior to index were associated with increased hospitalization risk.ConclusionsThere were no significant differences in the risk of ILD and its related complications between RA patients receiving anti-TNFα agents and those receiving alternate MOA agents. Further studies are needed that account for differences in baseline characteristics in order to fully evaluate the risk of ILD and its complications.
Highlights
Interstitial lung disease (ILD) is a common extra-articular condition in rheumatoid arthritis (RA), but few studies have systematically investigated its incidence and risk factors in patients receiving anti-tumor necrosis factor-alpha agents or alternate mechanisms of action (MOAs) (e.g., T-cell, B-cell, and interleukin-6 inhibitors)
Patient characteristics Patients without a history of ILD Despite differences in the ILD detection rate associated with each ILD definition, there was little variability in patient characteristics
Few studies have examined the risk of incident ILD among patients exposed to anti-Tumor necrosis factor (TNF), abatacept, rituximab, and tocilizumab, and even fewer studies have evaluated the risk of hospitalization in patients with preexisting ILD who are subsequently exposed to these agents
Summary
Interstitial lung disease (ILD) is a common extra-articular condition in rheumatoid arthritis (RA), but few studies have systematically investigated its incidence and risk factors in patients receiving anti-tumor necrosis factor-alpha (anti-TNFα) agents or alternate mechanisms of action (MOAs) (e.g., T-cell, B-cell, and interleukin-6 inhibitors). Half of patients with rheumatoid arthritis (RA) will have some form of extra-articular involvement, such as interstitial lung disease (ILD) [1,2,3]. Depending on the specific disease in question, the alveoli, airways, blood vessels, and pleura may be affected. Manifestations of ILD include respiratory symptoms (e.g., dyspnea and nonproductive cough), specific chest radiographic abnormalities, decreased lung volume, and microscopic patterns of inflammation and fibrosis [4]. Symptoms may be subtle or non-existent at onset, despite patients having radiographic features consistent with ILD
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