Thalidomide for the Treatment of Cough in Idiopathic Pulmonary Fibrosis

Mr, Horton; Santopietro,; Mathew, Lazar; Km, Horton; Aj, Polito; Liu, MC; Danoff, Sonye K.; Lechtzin, Noah

doi:10.7326/0003-4819-157-6-201209180-00003

Cited by 185 publications

(147 citation statements)

References 37 publications

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“…HORTON et al [15] found that thalidomide improved cough-specific QoL in IPF patients, although no objective cough measurements were assessed. Furthermore, thalidomide is known to have a toxic side-effect profile.…”

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confidence: 99%

Effect of Pirfenidone on cough in patients with Idiopathic Pulmonary Fibrosis

et al. 2017

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Idiopathic pulmonary fibrosis (IPF) is a progressive, fatal lung disease. In patients with IPF, cough is one of the most disabling symptoms and is an independent predictor of disease progression [1][2][3]. Cough in IPF is often non-responsive to antitussive therapy [4], and studies on cough are scarce and have unfortunately not yet resulted in effective treatments. Several observations suggest that pirfenidone, an anti-fibrotic drug, might decrease cough [5, 6]. We aimed to measure objectively the effect of pirfenidone on cough in patients with IPF and substantial cough. In addition, we assessed the effect of pirfenidone on subjective cough and quality of life (QoL) measures.This international, multicentre, prospective, observational study at four sites (The Netherlands, Italy, France and UK) recruited patients between 2013 and 2016. Treatment-naïve IPF patients aged 40-85 years with a forced vital capacity (FVC) ⩾50% and corrected transfer factor of the lung for carbon monoxide (TLCOc) ⩾30%, in whom pirfenidone therapy was about to be initiated according to regular practice, who had daily IPF-related cough for ⩾8 weeks with a cough score of ⩾40 mm on a 0-100 mm visual analogue scale (VAS), were eligible for the present study.Patients underwent baseline 24-h cough recording with the Leicester Cough Monitor (LCM) prior to starting pirfenidone, and after 4 and 12 weeks of treatment. The LCM is a validated ambulatory cough monitoring system [7]. Recordings were centrally analysed with automated cough software as previously described [7]. On the days of cough recording, participants completed the Leicester Cough Questionnaire (LCQ, a cough-specific health status questionnaire), the VAS cough severity, VAS urge-to-cough, King's Brief Interstitial Lung Disease health status questionnaire (K-BILD), the Hospital Anxiety and Depression Scale (HADS) and the seven-item Generalised Anxiety Disorder screener (GAD-7) [8,9].Analyses were performed on the intention-to-treat population. Objective cough frequency data were log transformed. To assess the effect of pirfenidone on cough over time we used a linear mixed model, which accounts for missing data [10]. Sensitivity analyses were performed on the per protocol population with a linear mixed model and paired t-tests. SPSS Statistics version 21.0 and R version 3.2.2 software packages were used for statistical analysis. The study was approved by the ethics committees of all participating centres (clinical trials.gov, NCT02009293). All patients provided written informed consent.Of the 46 patients screened for the study, 43 patients were included. Reasons for exclusion were low TLCOc and/or VAS scores. 38 patients completed 4 weeks of the study, and 31 completed 12 weeks. Reasons for dropout included: cessation of pirfenidone because of adverse events (8), logistic reasons (2), change of proton pomp inhibitor (1) and death (1). The age of the patients was 72±7 (mean±SD); most were men (33, 77%) and former smokers (34, 79%). Baseline cough counts, questionnaire scores and pulmonar...

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confidence: 99%

Effect of Pirfenidone on cough in patients with Idiopathic Pulmonary Fibrosis

et al. 2017

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“…Of the 24 randomized participants, 23 were treated (one left the study because of lack of interest), and 20 completed both treatment periods (three dropped out because of worsening health). The demographic characteristics of participants are shown in Table 1 , and further details about the study population can be found in Horton et al 10 Table 2 shows the baseline values of CQLQ, CQLQ subscales, cough VAS, and SGRQ. The CQLQ values are similar to those reported by French et al 9 in their original evaluation of the CQLQ in patients with acute and chronic cough.…”

Section: Resultsmentioning

confidence: 99%

“…Compared with placebo, the mean CQLQ score was 11.4 points lower in the treatment phase and, thus, exceeded this MID. 10 …”

Section: Randomization and Interventionsmentioning

confidence: 99%

Validation of the Cough Quality-of-Life Questionnaire in Patients With Idiopathic Pulmonary Fibrosis

Lechtzin

Hilliard

Horton

2013

Chest

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“…Knobloch et al (55) reported that the underlying mechanisms of this effect included downregulation of bone morphogenetic protein signaling, an increase in the activity of Wnt and Akt and enhanced apoptosis resistance. In a clinical trial conducted by Horton et al (56), thalidomide treatment was demonstrated to improve coughing and respiratory symptoms, as well as quality of life, in patients with IPF.…”

Section: Role Of Imids In Fibrosis Disease and Ophthalmopathymentioning

confidence: 99%

Thalidomide and its analogues: A review of the potential for immunomodulation of fibrosis diseases and opthalmopathy (Review)

et al. 2017

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Abstract. The US Food and Drug Administration approved thalidomide and its analogues for the treatment of erythema nodosum leprosum, in spite of the notoriety of reports of severe birth defects in the middle of the last century. As immunomodulatory drugs, thalidomide and its analogues have been used to effectively treat various diseases. In the present review, preclinical data about the effects of thalidomide and its analogues on the immune system are integrated, including the effects of cytokines on transdifferentiation, the anti-inflammatory effect, immune cell function regulation and angiogenesis. The present review also investigates the latest developments of thalidomide as a therapeutic option for the treatment of idiopathic pulmonary fibrosis, skin fibrosis, and ophthalmopathies.

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Thalidomide for the Treatment of Cough in Idiopathic Pulmonary Fibrosis

Abstract: Celgene Corporation.

Cited by 185 publications

References 37 publications

Effect of Pirfenidone on cough in patients with Idiopathic Pulmonary Fibrosis

Effect of Pirfenidone on cough in patients with Idiopathic Pulmonary Fibrosis

Validation of the Cough Quality-of-Life Questionnaire in Patients With Idiopathic Pulmonary Fibrosis

Thalidomide and its analogues: A review of the potential for immunomodulation of fibrosis diseases and opthalmopathy (Review)

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