Patient expectations, experiences and satisfaction with nintedanib and pirfenidone in idiopathic pulmonary fibrosis: a quantitative study

Idiopathic pulmonary fibrosis (IPF) is a rare, progressive interstitial lung disease with a poor prognosis [1]. Two antifibrotic drugs, nintedanib and pirfenidone, are available for treatment of IPF. These drugs slow down disease progression, may reduce the rate of acute exacerbations, and seem to prolong survival [2‐4]. The decision to prescribe either nintedanib or pirfenidone is usually based on the specific side-effect profiles, comorbidities, co-medication, and a patient’s preferences [5, 6]. The prevalence of adverse events has been reported in randomized controlled trials and registries with real-world data. In these studies, around 20–30% of patients permanently discontinued antifibrotic treatment due to adverse events, such as diarrhea or photosensitivity [7, 8]. Although efficacy and adverse events have been well studied, little is known about patient experiences and satisfaction with antifibrotic medication. Earlier qualitative studies suggested that experiences and satisfaction with medication were relatively positive in most patients [9‐11]. Patients with side-effects reported to have lower satisfaction levels and an impaired (health-related) quality of life ((HR)QOL) [10]. Studies in other chronic diseases showed that patient satisfaction with medication can influence health-related decisions and compliance with medication [12, 13]. Consequently, experiences and satisfaction with medication may also affect long-term treatment outcomes [12]. Moreover, expectations before start of treatment are associated with outcomes and satisfaction in other chronic conditions [14]. Gaining better insights in patient expectations before start of treatment could help to optimize expectation management and aid shared-decision making [14].

In recent years, it has been increasingly acknowledged that the patient perspective should play a central role in treatment decisions in IPF [6, 15]. Shared-decision making is only possible if patients’ needs, expectations, experiences, and preferences are regularly (re) assessed during the disease course. To allow for structured collection and evaluation of patient expectations and experiences with pharmacological treatment, the patient experiences and satisfaction with medication (PESaM) questionnaire has recently been developed and validated in IPF [11, 15].

In this study, we aimed to evaluate patient expectations, experiences, and satisfaction with antifibrotic treatment using the PESaM questionnaire. Furthermore, we compared PESaM scores between patients using nintedanib and pirfenidone, evaluated the relationship between (health-related) quality of life and satisfaction with medication, and assessed which factors were associated with overall medication satisfaction.

A total of 90 patients were included, of whom 43% used nintedanib and 57% pirfenidone. Of these patients, 83 completed the PESaM at baseline, 83 after three months, and 78 after six months. Baseline characteristics were comparable between both groups, except for FVC (Table 1). During the study, two patients died, five patients discontinued antifibrotic treatment due to side-effects, and seven patients switched medication.

In this study, we evaluated patient expectations, experiences and satisfaction with antifibrotic medication in patients with IPF, as this could aid future shared-decision making. To our knowledge, this was the first study in IPF which systematically assessed patient experiences with medication, using the validated PESaM questionnaire [15]. Patient experiences and satisfaction after three and six months of antifibrotic treatment were fairly positive, and similar in nintedanib and pirfenidone. Satisfaction with medication had a moderate positive correlation with (HR)QOL. Self-reported experiences with the effectiveness of the medication (e.g. positive impact on physical health, daily activities) was the main factor associated with overall medication satisfaction. Anxiety, depression, symptom scores, FVC change over time, experiences with side-effects, and perceived severity of side-effects were not associated with overall medication satisfaction after six months on multivariable analysis.

Interestingly, patients considered effectiveness of their medication more important than side-effects and ease of use. This is in line with findings from a recent study, which found that IPF patients were more concerned about slowing down disease progression than about side-effects. In contrast, almost a quarter of the surveyed healthcare providers in that study considered side-effects more important than the risk of disease progression [9]. Our results highlight the importance of shared-decision making, taking into account patients’ expectations, experiences and preferences in all treatment decisions, as patients’ opinions and considerations may be different than healthcare providers assume. In some settings, patients with a FVC above 80% do not receive antifibrotic treatment, either due to reimbursement restrictions or perceived barriers of doctors about early treatment [9]. In the current study, the mean FVC in the nintedanib group was 86%. Importantly, patient experiences and satisfaction with antifibrotic medication were also positive in this patient group with relatively high FVC, again underlining that from the patients’ perspective there is no rationale to delay treatment until lung function has declined below a FVC of 80%.

Overall, expectations regarding effectiveness were slightly higher than consecutive experiences, which emphasizes the need for realistic patient education and expectation management during the disease course [14]. Expectations and consecutive experiences with side-effects were comparable. There were no differences across participating centers. Expectation management may be complex in IPF, due to the heterogeneous disease course and the fact that antifibrotic medication does not halt or reverse lung function decline. Hence, it may be difficult for patients and their healthcare providers to judge the effectiveness of these drugs. This was reflected in the fact that a substantial number of patients answered that they did not know what to expect, and were uncertain whether treatment was effective. Nevertheless, the perceived effectiveness of medication was the only factor which was associated with overall medication satisfaction in a multivariable model. Patients’ beliefs and opinions regarding the effectiveness of their medication are factors known to impact medication adherence in other diseases [20]. In the present study, (self-reported) adherence with medication was very high. Thus, it could be speculated that uncertainty about effectiveness had no major influence on adherence. However, the design of the current study did not allow us to formally address this issue. Moreover, only a small minority of patient discontinued treatment (5.5%). The high adherence and low discontinuation rate could possibly be due to the relative short study duration. Longer prospective studies are needed to assess whether perceived effectiveness and satisfaction with medication affects long-term compliance and treatment outcomes [12, 15].

Previous studies have shown that nintedanib and pirfenidone have a similar effect on lung function decline. Furthermore, no significant differences in all-cause mortality and frequency of side-effects were found between the two drugs [2, 3, 5, 21]. However, these studies did not compare patient experiences and satisfaction between both antifibrotic drugs. Results of our study showed that self-reported experiences and satisfaction were similar in patients using nintedanib and pirfenidone. One could have speculated that the perceived ease of use would be different, because of the differences in dosing schedule. However, experiences and satisfaction with ease of use were very high in both groups, showing that patients considered it relatively easy to integrate the use of antifibrotic medication in their daily life. Although the side-effect profile was different for both drugs (e.g. more diarrhea in patients using nintedanib, more skin problems in patients using pirfenidone), the number and perceived severity of side-effects were similar. Use of structured tools like PESaM could facilitate insights into expectations, experiences and satisfaction in individual patients, and thereby guide decisions on treatment choices and adjustments throughout the disease course.

A strength of this study was that data were prospectively collected in a multi-center population of newly treated patients. Due to this multi-center design with multiple healthcare providers, potential differences in patient education about medication have been taken into account. This study has also limitations. The PESaM questionnaire has been developed and validated in IPF, but no minimal important difference and responsiveness has been established yet. Thus, further studies are needed to better explore clinical relevance of differences between patient expectations and experiences.

Patient experiences and satisfaction with medication after three and six months of antifibrotic treatment were relatively positive, and comparable between nintedanib and pirfenidone. Patient expectations before start of treatment were high, emphasizing the need for realistic expectation management. Perceived effectiveness of medication was associated with overall medication satisfaction. The PESaM questionnaire is a novel, simple tool to evaluate patient satisfaction and experiences with medication, and can be used both in clinical trials and in daily practice. We believe that systematic evaluation of patient experiences could enhance shared-decision making and guide treatment decisions in the future.