Infliximab Therapy in Pulmonary Sarcoidosis

Abstract

In their article, Baughman and colleagues (1) reported that infliximab therapy in patients with chronic sarcoidosis was associated with a significant improvement in percent predicted FVC after 24 weeks of therapy in a cohort of 138 patients. However, no benefit was demonstrated on the endpoints of the six-minutewalk test (6MWT), St. George’s Respiratory Questionnaire (SGRQ), or Borg’s CR10 dyspnea score. Post hoc analyses further suggested a greater benefit in patients with more severe disease. The authors conclude that the clinical relevance of the observedFVC improvement remains unclear. Nevertheless, they suggest that their data support further evaluation of anti–TNFtherapy in severe chronic sarcoidosis. In our opinion, the conclusions are too optimistic. This may lead to an uncontrolled use of infliximab in patients with chronic pulmonary sarcoidosis outside new study protocols. First, there is a clear limitation of the study in using FVC percent predicted as primary endpoint. Pulmonary function tests characteristically reveal a restrictive pattern with a reduction in DlCO, although it is not unusual for lung function to be normal (2). Endobronchial sarcoidosis may lead to impairment of airflow and obstructive respiratory physiology. There might be several reasons for a decrease in FVC—for example, bad performance or obesity. Measurement of TLC, RV, and DlCO might be more powerful in reflecting improvement of lung function. In our opinion, measurement of dynamic lung volumes is insufficient to reflect the changes occurring in sarcoidosis with pulmonary involvement. An improvement of 2.8% FVC percent predicted corresponds to an absolute increase of only about 0.080 L. Furthermore, endobronchial disease exists in approximately 70% of patients with stage II or III disease. Thus, changes in FEV1 would also be of interest (not mentioned in the article). Even the improvement in radiological findings remains questionable. There is no indication of the severity of sarcoidosis in the study population investigated.A radiological classification of patients into stages II to IVmight be helpful. Furthermore, a computed tomography scan would be more helpful to observe changes in radiological findings concerning both pulmonary involvement and the status of hilar and mediastinal lymphadenopathy. The study protocol has shown that the use of infliximab in these patients seems to be safe. On the other hand, O’Shea and colleagues reported the development of pulmonary sarcoidosis occurring in the context of infliximab treatment for ankylosing spondylitis (3). Since the study design shows several limitations, the investigators cannot suggest a potential beneficial effect of this expensive drug or propose further evaluation.