Patient preferences for the treatment of paroxysmal nocturnal hemoglobinuria: Interim results of a patient survey of ravulizumab (ALXN1210) and eculizumab

Background: Since 2007, eculizumab has transformed the management of paroxysmal nocturnal hemoglobinuria (PNH). However, it has a treatment burden associated with q2w dosing. Recently, the FDA approved ravulizumab for PNH treatment. Ravulizumab administered q8w demonstrated noninferiority to eculizumab in two phase 3 trials on all primary and key secondary efficacy measures. In view of these two treatment options, it is important to consider patient preference in determining a treatment plan for these patients (pts). Aims: To assess patient preference for ravulizumab or eculizumab treatment, in clinical trial substudy ALXN1210‐PNH‐302 s. Methods: The substudy enrolled PNH pts who participated in the extension period of the phase 3 study (ALXN1210‐PNH‐302) and provided informed consent. In the phase 3 study, adult PNH pts stable on eculizumab for at least 6 months received ravulizumab or eculizumab in accordance with protocol for 26 wks (randomized period). All pts in the extension period received ravulizumab. In the substudy, patient treatment preference was evaluated at one time point using an 11‐item PNH‐specific Patient Preference Questionnaire (PNH‐PPQ © ). Prior to the administration of the PNH‐PPQ, pts must have received at least two doses of ravulizumab during the extension period. Differences in preference between ravulizumab and eculizumab were examined with an exact binomial test (Q1), frequency distributions (Q2–3), and paired t‐tests (Q4–11), with P < 0.05 considered statistically significant. Standardized effect sizes ( d ) were calculated for differences between evaluations of ravulizumab and eculizumab on Q4‐11. Results: Of 98 pts enrolled, 95 pts from 8 countries (European Union, North America, and Australia) completed PNH‐PPQs per protocol for analysis. The mean age of responders was 50 years (range: 22–78); 56% were male and 44% female. Mean time since diagnosis was 14 years (range: 2–48) and the mean number of days between the last randomized study treatment and completion of PNH‐PPQ was 306 (range: 196–457). Overall, 93% of pts (n = 88) preferred ravulizumab vs 7% (n = 7; P < 0.001) who had no preference (n = 6) or preferred eculizumab (n = 1) (Table). With regard to specific aspects of treatment, ravulizumab was widely preferred on frequency of infusions (98%), ability to plan activities (98%), overall quality of life (88%), convenience of receiving treatment (85%), and effectiveness of medication until the next infusion (78%). Among pts who preferred eculizumab or had no preference, side effects of treatment (n = 52; 55%) and anxiety related to infusions (n = 49; 51%) were the leading factors in determining their choice. Frequency of infusions was selected by the most respondents (n = 41; 43%) as the most important factor determining treatment preference, followed by overall quality of life (n = 22; 23%). Moderate to large effect sizes were observed for factors favoring ravulizumab over eculizumab, including the frequency of infusions disrupting everyday life ( d = –1.46, P < 0.001), feeling fatigued after infusions ( d = –0.56, P < 0.001), and being able to enjoy life while receiving treatment ( d = 0.88, P < 0.001). Summary/Conclusion: In this clinical substudy of eculizumab‐experienced PNH pts, a vast majority preferred ravulizumab due to reduced infusion frequency (q8w vs q2w), ability to plan activities, overall quality of life, convenience of treatment, and effectiveness of medication compared to eculizumab. The study had a global outreach and imparts important patient perspective for treatment of PNH when there is more than one treatment option. image