scholarly journals Long‐term treatment with nintedanib in Asian patients with idiopathic pulmonary fibrosis: Results from INPULSIS®‐ON

Respirology ◽  
2019 ◽  
Vol 25 (4) ◽  
pp. 410-416 ◽  
Author(s):  
Jin Woo Song ◽  
Takashi Ogura ◽  
Yoshikazu Inoue ◽  
Zuojun Xu ◽  
Manuel Quaresma ◽  
...  
Keyword(s):  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Term Treatment ◽  
Asian Patients ◽  
Long Term Treatment

scholarly journals Long-term treatment of patients with idiopathic pulmonary fibrosis with nintedanib: results from the TOMORROW trial and its open-label extension

Thorax ◽  
2017 ◽  
Vol 73 (6) ◽  
pp. 581-583 ◽  
Author(s):  
Luca Richeldi ◽  
Michael Kreuter ◽  
Moisés Selman ◽  
Bruno Crestani ◽  
Anne-Marie Kirsten ◽  
...  
Keyword(s):  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Term Treatment ◽  
Adverse Event Profile ◽  
Open Label ◽  
Comparator Group ◽  
Long Term Treatment ◽  
Open Label Extension ◽  
Rate Of Decline

The TOMORROW trial of nintedanib comprised a randomised, placebo-controlled, 52-week period followed by a further blinded treatment period and an open-label extension. We assessed outcomes across these periods in patients randomised to nintedanib 150 mg twice daily or placebo at the start of TOMORROW. The annual rate of decline in FVC was −125.4 mL/year (95% CI −168.1 to −82.7) in the nintedanib group and −189.7 mL/year (95% CI −229.8 to −149.6) in the comparator group. The adverse event profile of nintedanib remained consistent throughout the studies. These results support a benefit of nintedanib on slowing progression of idiopathic pulmonary fibrosis beyond 52 weeks.

JAK1-dependent transphosphorylation of JAK2 limits the antifibrotic effects of selective JAK2 inhibitors on long-term treatment

2017 ◽  
Vol 76 (8) ◽  
pp. 1467-1475 ◽  
Author(s):  
Yun Zhang ◽  
Ruifang Liang ◽  
Chih-Wei Chen ◽  
Tatjana Mallano ◽  
Clara Dees ◽  
...  
Keyword(s):  
Pulmonary Fibrosis ◽  
Chronic Treatment ◽  
Term Treatment ◽  
Janus Kinase ◽  
Prolonged Treatment ◽  
Therapeutic Effects ◽  
Long Term Treatment ◽  
Jak2 Inhibition ◽  
Jak2 Inhibitors

ObjectivesJanus kinase 2 (JAK2) has recently been described as a novel downstream mediator of the pro-fibrotic effects of transforming growth factor-β. Although JAK2 inhibitors are in clinical use for myelodysplastic syndromes, patients often rapidly develop resistance. Tumour cells can escape the therapeutic effects of selective JAK2 inhibitors by mutation-independent transactivation of JAK2 by JAK1. Here, we used selective JAK2 inhibition as a model to test the hypothesis that chronic treatment may provoke resistance by facilitating non-physiological signalling pathways in fibroblasts.MethodsThe antifibrotic effects of long-term treatment with selective JAK2 inhibitors and reactivation of JAK2 signalling by JAK1-dependent transphosphorylation was analysed in cultured fibroblasts and experimental dermal and pulmonary fibrosis. Combined JAK1/JAK2 inhibition and co-treatment with an HSP90 inhibitor were evaluated as strategies to overcome resistance.ResultsThe antifibrotic effects of selective JAK2 inhibitors on fibroblasts decreased with prolonged treatment as JAK2 signalling was reactivated by JAK1-dependent transphosphorylation of JAK2. This reactivation could be prevented by HSP90 inhibition, which destabilised JAK2 protein, or with combined JAK1/JAK2 inhibitors. Treatment with combined JAK1/JAK2 inhibitors or with JAK2 inhibitors in combination with HSP90 inhibitors was more effective than monotherapy with JAK2 inhibitors in bleomycin-induced pulmonary fibrosis and in adTBR-induced dermal fibrosis.ConclusionFibroblasts can develop resistance to chronic treatment with JAK2 inhibitors by induction of non-physiological JAK1-dependent transactivation of JAK2 and that inhibition of this compensatory signalling pathway, for example, by co-inhibition of JAK1 or HSP90 is important to maintain the antifibrotic effects of JAK2 inhibition with long-term treatment.

scholarly journals Long-term clinical and real-world experience with pirfenidone in the treatment of idiopathic pulmonary fibrosis

2015 ◽  
Vol 24 (135) ◽  
pp. 58-64 ◽  
Author(s):  
Vincent Cottin ◽  
Toby Maher
Keyword(s):  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Adverse Events ◽  
Real World ◽  
Sun Exposure ◽  
Progression Free Survival ◽  
Primary Treatment ◽  
Lung Function Decline ◽  
Long Term Treatment

Idiopathic pulmonary fibrosis (IPF) is a chronic, irreversible, progressively destructive lung disease that culminates in respiratory failure and death. Randomised controlled trials have demonstrated that treatment of IPF patients with pirfenidone reduces lung function decline, improves progression-free survival and significantly reduces the risk of all-cause mortality at 1 year. Pirfenidone has been shown to have a favourable safety profile and was generally well tolerated over the long term in clinical trials and real-world experience. However, side-effect management is critical to help some patients remain on treatment over the long term. The primary treatment-related adverse events associated with pirfenidone therapy are gastrointestinal upset, rash and photosensitivity. Gastrointestinal events may be mitigated by ensuring that pirfenidone is taken with food, while skin symptoms may be reduced by avoiding sun exposure and frequent use of sunblock. Educating patients about the potential for these adverse events to occur and providing instructions prior to treatment to avoid adverse drug reactions are an important means of ensuring patients may derive the important benefits provided by long-term treatment with pirfenidone.

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