Erdnussprotein als entfettetes Pulver von Arachis hypogaea L., semen (Erdnüsse) (1) – Palforzia®

• Clinical trials
  • The benefit assessment is based on the two double-blind RCTs PALISADE (ARC003) and ARTEMIS (ARC010). The ARC003 and ARC010 studies are both randomised, double-blind trials investigating the safety and efficacy of immunotherapy with peanut protein in the form of defatted powder from Arachis hypogaea L., semen (peanuts) (in short: peanut protein) compared with placebo.

Patients aged 4 to 17 years with a confirmed diagnosis of peanut allergy, as well as patients who turn 18 during the course of treatment

• For patients with a confirmed diagnosis of peanut allergy aged between 4 and 17 years, as well as patients who turn 18 during treatment, the additional benefit of peanut protein in the form of defatted powder from Arachis hypogaea L., semen (peanuts) does not provide proof for patients aged 4 to 17 years with a confirmed diagnosis of peanut allergy, as well as patients who turn 18 during treatment, compared with a ‘wait-and-see’ approach.
• mortality
  • Overall mortality
  • No deaths occurred in the ARC003 and ARC010 studies.
• morbidity
  • Allergic reactions following accidental exposure to peanuts
  • For the endpoint of allergic reactions following accidental exposure to peanuts, there was no statistically significant difference between the treatment groups.
  • Symptom-free status at all tested doses (up to 1000 mg) in the exit DBPCFC (double-blind, placebo-controlled food challenge)
  • For the endpoint ‘absence of symptoms at all tested doses (up to 1000 mg) in the Exit-DBPCFC’, there is a statistically significant advantage of peanut protein over a watch-and-wait approach.
  • Although an advantage of peanut protein over placebo was observed with regard to freedom from symptoms in the Exit-DBPCFC, this is not reflected in the patient-relevant endpoint of allergic reactions following accidental exposure to peanuts, which is independent of the provocation testing.
  • Maximum symptom severity across all tested doses of peanut protein in the Exit-DBPCFC
  • For the endpoint ‘Maximum symptom severity at all tested doses of peanut protein in the Exit-DBPCFC’, there is a statistically significant advantage of peanut protein over a watch-and-wait approach.
• Health-related quality of life
  • Notwithstanding the assessment of the validity of the instruments, the use of the FAQLQ and FAIM instruments in the studies is not suitable for adequately assessing patient-reported morbidity/health-related quality of life in this indication.
  • Overall, therefore, no usable data are available on health-related quality of life.
• Side effects
  • Serious adverse events (SAEs), serious adverse events
  • For the endpoints SUE and severe AEs, there were no statistically significant differences between the treatment groups.
  • Discontinuation due to AEs
  • For the endpoint ‘discontinuation due to AEs’, there is a statistically significant difference in favor of soy protein compared with a ‘wait-and-see’ approach that has no disadvantage.
  • Specific adverse events
  • For the endpoint ‘systemic allergic reactions’, there is a statistically significant difference in favour of peanut protein compared with a ‘wait-and-see’ approach that has no advantage.
  • For the endpoint ‘severe systemic allergic reactions’, however, there was no statistically significant difference between the treatment groups.
  • For the endpoints abdominal pain, upper abdominal pain, itching in the mouth, oral paraesthesia, tightness in the throat (PT and AE respectively) and disorders of the ear and labyrinth (SOC, AE), a statistically significant difference was observed to the disadvantage of peanut protein compared with a watch-and-wait approach.
  • The observed disadvantages of peanut protein – with the exception of discontinuations due to upper abdominal pain – are evident not only during the initial dose-escalation phase but also occur during the maintenance phase.
• Overall assessment / Conclusion
  • In summary, within the morbidity endpoint category, the endpoints recorded during the DBPCFC exit challenge testing – namely ‘absence of symptoms at all tested doses’ and ‘maximum symptom severity at all tested doses of peanut protein’, treatment with peanut protein showed statistically significant advantages over a ‘wait-and-see’ approach.
  • In the patient-relevant endpoint “allergic reactions following accidental exposure to peanuts”, which is independent of the challenge testing, no statistically significant advantages or disadvantages were observed.
  • No usable data are available for the category of health-related quality of life.
  • In the category of side effects, disadvantages can be inferred for treatment with peanut protein compared with the appropriate comparator therapy (watchful waiting).
  • Overall, treatment with peanut protein shows advantages in the symptom-related endpoints within the context of provocation testing under study conditions; however, these could not be confirmed in patient-relevant endpoints outside the context of provocation testing.
  • In its weighting decision, the G-BA concludes that, in this case, neither the disadvantages regarding side effects nor the advantages—which are evident exclusively in morbidity endpoints within the context of the food challenge (DBPCFC)—prevail.
  • Consequently, for patients aged 4 to 17 with a confirmed diagnosis of peanut allergy, as well as patients who turn 18 during treatment, the additional benefit compared with the appropriate comparator therapy of watchful waiting is not proven.

Courtesy translation only, please refer to the German original.