Real-world results from the largest analyses of Vertex Pharmaceutical’s cystic fibrosis’ treatment Kalydeco (ivacaftor) done in CF patients to date confirm the therapy’s ability to significantly lower the risks of mortality, transplants, hospitalization, and pulmonary exacerbations compared to untreated patients.
These results were presented today at the 41st European Cystic Fibrosis Society (ECFS) Conference, taking place through June 9 in Belgrade, Serbia, in a presentation titled, “Disease progression in patients with cystic fibrosis treated with ivacaftor: analyses of real-world data from the US and UK cystic fibrosis Registries.”
Researchers used real-world data from two CF registries — one in the U.S. and one in the U.K. — to evaluate the long-term impact of Kalydeco on disease progression.
They analyzed data from a subset of patients, none with a lung transplant, undergoing treatment with Kalydeco for five (U.S. group) and four years (U.K.) — dating to when the treatment became available in each country. Data from these patients were compared to that of age-, sex-, and disease severity-matched CF patients not using Kalydeco.
Researchers evaluated several parameters in each group, namely: lung function (measured by the percent predicted forced expiratory volume in 1 second, ppFEV1), the rate of pulmonary exacerbations and hospitalizations, and infection with the bacteria Pseudomonas aeruginosa, the most important pathogen in progressive and severe CF lung disease.
Additional measures included body mass index (a measure of body fat), and the number of CF-related complications (such as CF-related diabetes).
The U.S. cohort included 635 patients treated with Kalydeco and 1,874 controls; U.K. data covered 247 treated patients and 1,230 controls.
In the U.S., patients treated with Kalydeco for five years show a better performance on lung function tests — their mean change in ppFEV1 was -0.7 percentage points compared to -8.3 in the control group. Lung function improvement was seen in U.K. patients after four years of treatment — a mean change in ppFEV1 of +4.9 percentage points compared to -4.3 in the control group.
The rate of pulmonary exacerbations was also lower in Kalydeco-treated U.S. patients after 5 years — dropping from 37.5% to 25.7%. At four years of treatment, the U.K. patients showed a decrease from 53.8% to 32.8%. In contrast, patients in both countries not using Kalydeco showed increasing rates of pulmonary flares: from 33.1% to 44.0% over five years in the U.S., and from 45.2% to 57.5% over four years in the U.K.
In terms of body mass, the mean change was +2.4 kg/m2 in Kalydeco-treated patients in the U.S. compared to +1.6 in controls. A similar trend was also observed in the U.K. registry, with a mean change of +1.9 kg/m2 in the Kalydeco group versus +0.9 in other CF patients.
Treatment with Kalydeco also led to a fewer hospitalizations, and a less prevalence of Pseudomonas aeruginosa and CF-related diabetes in patients in both countries compared to controls.
The rate of hospitalizations decreased by 11.5% (U.S.) and by 20.7% (U.K.) in the Kalydeco groups, while it increased in both control groups.
A lower prevalence of P. aeruginosa was especially noticeable in the U.K. registry, where the bacterial burden dropped in treated patients from 63.2% to 38.9% over the four years. Among patients treated for five years in the U.S., prevalence fell from 56.5% to 45.1%.
In a more comprehensive analysis of patients in each registry, researchers also found that Kalydeco-treated patients had a significantly smaller mortality risk compared to controls in both the U.S. (0.4% vs 1%, respectively), and the U.K. (0.4% vs 0.9%).
The same significant trend was observed for transplant rates, with controls undergoing more transplants than Kalydeco-treated patients — 1.1% vs 0.3% in the U.S., respectively, and 0.9% vs 0.2% in the U.K.
Regarding safety, no new safety concerns were identified.
The results were shared in a presentation titled “Real-world outcomes in patients with cystic fibrosis treated with ivacaftor: 2016 US and UK cystic fibrosis Registry analyses.”
Taken together, “analysis of data from 2 large, independent registries showed better preserved lung function, improved nutritional measures, decreased risk of PEx [pulmonary exacerbations] and hospitalizations, and favorable trends in prevalence of CF complications and P. aeruginosa prevalence in patients treated with Kalydeco” the researchers wrote.
These real-world results support the long-term benefits of Kalydeco as a disease-modifying treatment, they concluded.