Potential risk of TNF inhibitors on the progression of interstitial lung disease in patients with rheumatoid arthritis

Abstract

ObjectivesBiological therapy represents important advances in alleviating rheumatoid arthritis (RA), but the effect on interstitial lung disease (ILD) has been controversial. The objective of this study was to assess the risk of such treatment for patients with ILD.DesignCase–control cohorts.SettingSingle centre in Japan.ParticipantsThis study included 163 patients with RA who underwent biological therapy.Outcome measuredWe assessed chest CT before initiation of biological therapy and grouped 163 patients according to the presence of ILD (with (n=58) and without pre-existing ILD (n=105)). Next, we evaluated serial changes of chest CT after treatment and visually assessed the emergence of ILD or its progression, which was referred to as an ‘ILD event’. Then, we also classified the patients according to the presence of ILD events and analysed their characteristics.ResultsTumour necrosis factor (TNF) inhibitors were administered to more patients with ILD events than those without ILD events (88% vs 60%, p<0.05), but recipients of tocilizumab or abatacept did not differ in this respect. Of 58 patients with pre-existing ILD, 14 had ILD events, and that proportion was greater than for those without pre-existing ILD (24% vs 3%, p<0.001). Of these 14 patients, all were treated with TNF inhibitors. Four patients developed generalised lung disease and two died from ILD progression. Baseline levels of KL-6 were similar in both groups, but increased in patients with ILD events.ConclusionsTNF inhibitors have the potential risk of ILD events, particularly for patients with pre-existing ILD, and KL-6 is a valuable surrogate marker for detecting ILD events. Our data suggest that non-TNF inhibitors are a better treatment option for these patients.

Biological Drug Use in Patients with Psoriasis: Our Clinical Experiences

“…It is known that TNFα inhibitors promote subclinical interstitial lung disease. 12 In this study, the treatment in two patients using adalimumab and infliximab was terminated because of interstitial AC disease. Studies have shown that psoriasis is an independent risk factor in diseases such as diabetes, atherosclerosis, myocardial infarction and stroke.…”

Severe Acute Respiratory Distress Syndrome during Infliximab Therapy in a Patient with Crohn Disease

“…The study of Curtis et al [19] found that older patients, men, and patients with a history of other pulmonary disorders or recent exposure to glucocorticoids using tocolizumab, rituximab, abatacept, or anti-TNF-α agents were at increased risk for developing interstitial lung disease. The mechanisms of interstitial lung disease exacerbation after initiation of TNF-α-inhibitors are considered to be caused by the interaction of cytokine release upon these agents [20]. …”

Management of Connective Tissue Disease–associated Interstitial Lung Disease

“…4,5 There has been some evidence based on case reports, retrospective studies, and postmarketing surveillance that biologic DMARDs, particularly the anti-tumor necrosis factor (TNF) class, may be associated with an increased risk of pneumonitis. 1,[6][7][8] However, because no prospective controlled data exist and there is an appreciation that multiple variables, including the underlying CTD, are associated with ILD development, progression, or exacerbation, we suggest that these agents be used with caution in patients with CTD-ILD 1,[9][10][11] and other treatment options prioritized when possible. We frequently use the spectrum of biologic DMARDs in our patients with CTD-ILD to manage the extrathoracic manifestations and find that these agents often have minimal, if any, impact on the ILD.…”