Gastrointestinal involvement in systemic sclerosis

Savarino, Edoardo; Furnari, Manuele; Bortoli, Nicola de; Martinucci, Irene; Bodini, Giorgia; Ghio, Massimo; Savarino, Vincenzo

doi:10.1016/j.lpm.2014.03.029

Cited by 71 publications

(117 citation statements)

References 140 publications

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“…The known adverse effects of pirfenidone on the GI system, skin, and liver 17,18 were of interest in SSc-ILD because these organ systems are also affected in patients with SSc 1,24,25 . Although GI AE were common, this was not unexpected because of the high frequency of such events observed in clinical trials of pirfenidone in patients with IPF, although patients with moderate to severe gastroesophageal reflux disease (UCLA GIT reflux subscale score > 1.0) were excluded from our study.…”

Section: Discussionmentioning

confidence: 99%

“…Pirfenidone also significantly reduces the risk of mortality in patients with IPF compared with placebo and can benefit patient outcomes including the 6-min walking distance and dyspnea 17,23 . However, pirfenidone is known to be associated with adverse events (AE) of the liver, gastrointestinal (GI) system, and skin 17,18 , which may overlap with the organ systems frequently affected in patients with SSc 1,24,25 . Therefore, in the setting of SSc-ILD, it is important to investigate the tolerability of pirfenidone before assessing its efficacy.…”

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confidence: 99%

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An Open-label, Phase II Study of the Safety and Tolerability of Pirfenidone in Patients with Scleroderma-associated Interstitial Lung Disease: the LOTUSS Trial

Khanna

Albera²,

Fischer³

et al. 2016

J Rheumatol

227

126

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Objective.Systemic sclerosis-associated interstitial lung disease (SSc-ILD) shares a number of clinical features and pathogenic mechanisms with idiopathic pulmonary fibrosis (IPF). This study was designed to evaluate the tolerability of the IPF treatment pirfenidone in SSc-ILD. The known gastrointestinal, skin, and liver adverse events (AE) of pirfenidone are of importance given the involvement of these organs in SSc.Methods.All patients received pirfenidone and were randomized 1:1 to either a 2- or 4-week titration starting at 801 mg/day and finishing at a maintenance dose of 2403 mg/day. Patients received pirfenidone for 16 weeks in total. Assessments included treatment-emergent AE (TEAE) and exploratory disease outcomes.Results.Sixty-three patients were randomized; 96.8% experienced a TEAE and more patients reported TEAE during the titration versus the maintenance period. The most commonly reported TEAE were consistent with those observed for pirfenidone in IPF (nausea, headache, fatigue) and were similar regardless of titration schedule. More patients discontinued treatment because of TEAE in the 2- versus 4-week titration group (5 vs 1, respectively); all discontinuation events occurred > 3 weeks after reaching the full dose of pirfenidone. Mycophenolate mofetil (MMF), taken by 63.5% of patients in addition to pirfenidone, did not appear to affect tolerability. Exploratory disease outcomes remained largely unchanged.Conclusion.Pirfenidone showed an acceptable tolerability profile in SSc-ILD, although a longer titration may be associated with better tolerability. Tolerability was not affected by concomitant MMF. The present findings support further investigation of pirfenidone in future clinical trials in patients with SSc-ILD. Trial registration: ClinicalTrials.gov; www.clinicaltrials.govNCT01933334.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

An Open-label, Phase II Study of the Safety and Tolerability of Pirfenidone in Patients with Scleroderma-associated Interstitial Lung Disease: the LOTUSS Trial

Khanna

Albera²,

Fischer³

et al. 2016

J Rheumatol

227

126

View full text Add to dashboard Cite

show abstract

“…In LOTUSS, a longer titration schedule (4 weeks versus 2 weeks) was associated with better pirfenidone tolerability (table 2) [26]. The 4-week titration schedule was tested with pirfenidone in this specific population because patients with SSc-ILD may be more susceptible to GI-, skin-and liver-related AEs due to the nature of their disease [27,28]. Patients in the 2-week titration group had more dose modifications overall compared with the 4-week titration group during the titration period (dose reductions: 21.9% versus 3.2%, difference 18.7%, p=0.0534; dose interruptions: 12.5% versus 0%, difference 12.5%, p=0.1132) as well as more discontinuations due to a TEAE (15.6% versus 3.2%).…”

Section: Dose Titrationsmentioning

confidence: 99%

“…The SSc-ILD population is of particular interest for understanding how to manage pirfenidone-related AEs, because this group may be more susceptible to certain AEs and tolerability issues, particularly GI, skin and liver, due to the involvement of these organs in their disease [27,28].…”

Section: Introductionmentioning

confidence: 99%

Pirfenidone safety and adverse event management in idiopathic pulmonary fibrosis

et al. 2017

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Pirfenidone is one of two approved therapies for the treatment of idiopathic pulmonary fibrosis (IPF). Randomised controlled clinical trials and subsequent post hoc analyses have demonstrated that pirfenidone reduces lung function decline, decreases mortality and improves progression-free survival. Long-term extension trials, registries and real-world studies have also shown similar treatment effects with pirfenidone. However, for patients with IPF to obtain the maximum benefits of pirfenidone treatment, the potential adverse events (AEs) associated with pirfenidone need to be managed. This review highlights the well-known and established safety profile of pirfenidone based on randomised controlled clinical trials and real-world data. Key strategies for preventing and managing the most common pirfenidone-related AEs are described, with the goal of maximising adherence to pirfenidone with minimal AEs.

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“…In LOTUSS (NCT01933334), a phase II trial that investigated pirfenidone in systemic sclerosis ILD (SSc-ILD), a longer titration schedule (4 vs. 2 weeks) was associated with better tolerability of pirfenidone [18]. The 4-week titration schedule was tested with pirfenidone in this specific population because patients with SSc-ILD may be more susceptible to GI, skin, and liver-related AEs due to the nature of their disease [19,20]. Patients in the 2-week titration group had more dose modifications overall than those in the 4-week titration group during the titration period [18].…”

Section: Often or Always Effective (N = 44)mentioning

confidence: 99%

Real-World Practice Patterns for Prevention and Management of Potential Adverse Events with Pirfenidone in Patients with Idiopathic Pulmonary Fibrosis

Wencel

Limb²,

Stauffer³

et al. 2018

Pulm Ther

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Gastrointestinal involvement in systemic sclerosis

Cited by 71 publications

References 140 publications

An Open-label, Phase II Study of the Safety and Tolerability of Pirfenidone in Patients with Scleroderma-associated Interstitial Lung Disease: the LOTUSS Trial

An Open-label, Phase II Study of the Safety and Tolerability of Pirfenidone in Patients with Scleroderma-associated Interstitial Lung Disease: the LOTUSS Trial

Pirfenidone safety and adverse event management in idiopathic pulmonary fibrosis

Real-World Practice Patterns for Prevention and Management of Potential Adverse Events with Pirfenidone in Patients with Idiopathic Pulmonary Fibrosis

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