Nintedanib slows loss of lung function in limited cutaneous systemic sclerosis, ILD
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Key takeaways:
- Patients receiving nintedanib demonstrated slowed function deterioration compared with those receiving placebo.
- The researchers said the findings assert the value of prompt diagnoses.
Nintedanib slows the deterioration of lung functionality in patients with limited cutaneous systemic sclerosis and interstitial lung disease, according to data published in Rheumatology.
“Patients with [limited cutaneous SSc (lcSSc)] have been underrepresented in clinical trials, limiting the data available on the clinical course and treatment of these patients,” Yannick Allanore, MD, PhD, of Cochin Hospital, in Paris, and colleagues wrote. “Nintedanib has been licensed for the treatment of SSc-ILD, idiopathic pulmonary fibrosis (IPF) and other chronic fibrosing ILDs with a progressive phenotype.
“In the SENSCIS trial in patients with SSc-ILD, nintedanib reduced the rate of decline in forced vital capacity (FVC) (ml/year) over 52weeks by 44% vs placebo,” they added. “The SENSCIS trial enrolled a broad population of patients with SSc-ILD, including patients with lcSSc. Thus, the SENSCIS trial and its open-label extension, SENSCIS-ON, provide an opportunity to investigate the course of ILD and the effects of treatment specifically among patients with lcSSc.”
To analyze ILD course as well as the impacts of nintedanib (Ofev, Boehringer Ingelheim) in patients with limited cutaneous SSc, Allanore and colleagues conducted the SENCIS and SENCIS-ON trials. In the former trial, patients with SSc who experienced their first non-Raynaud symptom within the prior 7years — and also receiving prednisone 10mg per day or less and/or on stable therapy with mycophenolate or methotrexate for at least 6months — were randomized to receive either nintedanib 150mg twice daily or placebo. These patients remained on blinded treatment for at least 52 weeks but no more than 100 weeks.
Patients who completed SENCIS and completed a follow-up visit 28days later, or who completed a drug-drug interaction study of nintedanib plus oral contraceptive — in female patients with SSc-ILD — in which the drug provided for approximately 14 to 28days, were eligible to enter SENSCIS-ON. In this trial, all patients received open-lable nintedanib. Patients were categorized as having limited cutaneous SSc or diffuse cutaneous SSc prior to participating in one of the precursor trials.
For this analysis, main outcomes included change from baseline in forced vital capacity (FVC) as measured at 52 weeks in all patients with limited cutaneous SSc. In addition, the researchers analyzed the proportion of participants who registered a relative decline of FVC of more than 5% and 10%, as well as which patients were predicted to reach an absolute reduction of more than 5% or 10% by week 52.
A total of 183 patients with limited cutaneous SSc participated in SENCIS-ON and were eligible for analysis due to the availability of their week 52 data. The change in baseline of FVC through week 52 was –41.5 ml in patients who transitioned from placebo to nintedanib at the introduction of SENCIS-ON, and –45.1 ml in those who received nintedanib throughout the original SENCIS and SENCIS-ON trials, according to the researchers.
“These analyses of data from the SENSCIS trial indicate that patients with lcSSc may develop progressive pulmonary fibrosis within a few years of diagnosis of SSc,” Allanore and colleagues wrote. “Over 52 weeks, the rate of decline in FVC in patients with lcSSc and ILD was lower in patients treated with nintedanib than placebo, with adverse events that could be managed by most patients. These findings support the screening of patients with lcSSc for ILD and the importance of prompt initiation of treatment in patients with lcSSc-ILD to preserve lung function.”
Perspective
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David A. McLain, MD, MACR, FACP, FRCP
Interstitial lung disease is the leading cause of disease-related death in scleroderma. Prior to the advent of angiotensin-converting enzyme inhibitors, renal disease was the most dreaded manifestation of systemic sclerosis. The mortality rate for patients with SSc and lung fibrosis is nearly three times greater than those with SSc without lung fibrosis.
Studies of patients with SSc over the course of their disease estimate the range with ILD to be 30% to 90%, with autopsy studies showing up to 100% with some degree of lung fibrosis. This has been confirmed with high-resolution computed tomography, where up to 90% have interstitial changes. Pulmonary function test (PFT) abnormalities are seen in 40% to 75%. PFT trends at 1 and 2 years have been found to predict intermediate and long-term mortality. Onset is often rapid, with significant ILD found to develop in 25% of patients within 3 years of SSc diagnosis.
Risk factors for the development of ILD include African American race, male sex and cardiac involvement. Predictors of mortality from ILD are similar and have included male sex, a DLCO of less than 70%, cardiac involvement, C-reactive protein greater than 5 mg/L, severe skin involvement, forced vital capacity of less than 55%, and lung involvement — ILD or pulmonary arterial hypertension.
This paper illustrates the effectiveness of nintedanib (Ofev, Boehringer Ingelheim) in patients with SSc and ILD. This is the first medication approved by the FDA for this indication. It has been needed and is welcome. As the first drug in this class, adverse effects are higher than would be desired. Diarrhea, occurring in 76% of patients with SSc-ILD, has been a particularly challenging problem for my patients. We celebrate the success of a new medication and look for further development in this class.
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