Key study points:
1. Thalidomide treatment improved cough-specific quality of life and decreased cough severity in IPF patients compared to placebo treatment
2. Thalidomide also improved overall respiratory quality of life in IPF patients compared to placebo.
3. Patients receiving thalidomide demonstrated an increased risk of adverse events when compared to controls.
Primer: Idiopathic Pulmonary Fibrosis (IPF) is a disease that affects over 40 persons per 100000 people with no definitive treatment or cure and a median survival of 3-5 years after diagnosis.
Among patients suffering from IPF, cough is one of the most common symptoms reported. Studies have demonstrated that not only is non-productive, persistent cough incredibly distressing and disabling to patients, but it has been found to be an independent predictor of disease progression and outcomes (time to death or lung transplant). Unfortunately, typical cough-suppressing treatments such as opiods and topical airway analgesics have been largely ineffective in the treatment of IPF-related cough.
Immune dysregulation has long been considered to play a major role in disease pathogenesis and immunosuppressive medications have been a mainstay of IPF therapy. Recent studies looking at immunomodulators, such as interferon-alpha and thalidomide, for the treatment of IPF have noted that these drugs may have some effect in improving cough symptoms. In an effort to more specifically investigate the efficacy of thalidomide in the treatment of IPF-related cough, researchers at the Johns Hopkins University School of Medicine designed and conducted this clinical trial.
This [double-blinded, placebo-controlled crossover] trial: 24 patients were randomized receive thalidomide (n=12) or placebo (n=12). The first treatment period lasted for a total of 12 weeks and was then followed by a 2 week washout period before the groups were crossed over for the second 12-week treatment period. During each treatment period, patients were initially given a 50mg dose of the medication (thalidomide or placebo) and this dose was increased to 100mg if no improvement in cough occurred by week 2. Treatment efficacy was evaluated via the Cough Quality of Life Questionnaire (CQLQ), which looked at cough-related quality of life, a visual analog scale, which calculated cough severity, and the St. George’s Respiratory Questionnaire, which measured respiratory quality of life. Statistical analysis revealed several key findings:
In sum: The authors conclude that this study demonstrates “low dose thalidomide not only significantly improves cough in patients with IPF, as evidence by the improvement in CQLQ and visual analog scale scores, but also improves overall quality of life.”
However, the study does face some limitations. First, given the small number of participants and the single site studied, the results may not by representative of the whole patient population. Second, there was greater loss to follow up in the thalidomide group than in the control group, a potential source of bias, which the authors accounted for with sensitivity analysis. Third, the study duration of 3 months was relatively short and thus further study is needed to understand the long-term efficacy and adverse event profile of thalidomide treatment for IPF-related cough. Fourth, while the study was double-blinded, thalidomide’s unique side effect profile may have allowed some participants to identify the drug and thus introduce bias in their response and/or reports, a possibility that the authors did not address in their study. Finally, general health-related quality of life was not assessed and thus the effective of thalidomide side effects on overall health was not weighed against its effects on cough and respiratory quality of life. However, as all participants requested thalidomide when given the option at the end of the study, despite adverse outcomes experienced, the authors concluded that thalidomide’s benefits likely outweighed its side effects.
This study is the first clinical trial demonstrating efficacy in a treatment for IPF-related cough. The authors propose that a large-scale, multi-center trial would be the best next step in evaluating the long-term efficacy and safety of thalidomide in treating cough in IPF.