Chronic obstructive pulmonary disease (COPD) is a smoking related inflammatory lung disease. Tumor necrosis factor-alpha is thought to play an important role in the induction and maintenance of this inflammation. No effective anti-inflammatory agents are currently available to reduce airway inflammation in COPD. Aim: To evaluate the anti-inflammatory effect of the anti-TNF drug infliximab in patients with mild COPD.
22 current smokers with COPD (GOLD stage I/II) participated: 18 males, mean (SD) age 56 (6) years, packyears 58 (38), postbronchodilator FEV1 86 (12) % predicted. Baseline characteristics were similar in both groups. Design: an exploratory double-blind, placebo-controlled randomised trial. 14 patients received three infusions of infliximab (5 mg/kg) at week 0, 2 and 6. Sputum samples, Control of COPD Questionnaire (CCQ), exhaled Nitric Oxide and FEV1 were evaluated at day 1 (baseline) and 2, week 2, 6 and 8. Bronchial hyperresponsiveness to Adenosine 5’-Monophosphate (AMP) was measured at baseline and week 9.
Outcome variables (table 1)Table 1.
Values are presented as medians (ranges)infliximabCCQFEV1 % predictedSputum neutrophils (%)LOG2 PC20 AMPBaselineWeek 8BaselineWeek 8BaselineWeek 8BaselineWeek 9No1.2 (0.7–2.2)1.1 (0.7–2.3)77 (53–101)79 (57–101)68 (57–77)57 (50–82)2.6 (1.3–6.5)2.7 (–1.4–4.4)Yes1.1 (0.4–2.1)1.1 (0.3–1.7)78 (54–96)77 (46–93)67 (49–80)66 (18–92)2.4 (0.1–6.5)2.2 (–0.2–6.5)did not change significantly after treatment with infliximab compared to placebo. Exhaled Nitric Oxide increased significantly at day 2, week 6 and 8 in patients receiving infliximab versus controls. Sputum neutrophils decreased significantly after infliximab in patients with > 44 (median) packyears on day 2 from baseline [median (ranges) 71 (56–78) % to 53 (31–72) %], whereas in the placebo group no significant changes were observed [63 (57–71) to 61 (58–66) %]. No serious adverse events were reported within 9 weeks.
Our exploratory study, which was not powered, did not show a short-term effect of infliximab on respiratory symptoms as assessed by CCQ, FEV1 and sputum cell count in patients with mild COPD.
Before definite conclusions can be drawn as to the effectiveness of anti-TNF treatment in COPD, additional studies are needed with more severe COPD patients, larger groups and a longer follow-up.
H. van der Vaart, None.