Discussion
itching, AD, atopic diseases, eczema
MINOR, DISEASE, RECRUITMENT, ECZEMA
The CAMATOP II trial was strongly impacted by confinements and research restrictions due to the COVID-19 pandemic. However, in the 20 included AD patients, the authors observed partly relevant beneficial changes over time in perceived itching intensity, disease severity, and disease-specific QoL for HTP, IFDP, and partly also for control. One AE with aggravation of itching and eczema with the use of a topical immunomodulator was unsurely related to HTP; other AEs by patients related to HTP or IFDP were minor and short-lived, probably by focusing the patients' attention on the skin. Reported SAEs were not related to the interventions. The HTP and IFDP “in-presence” and online meetings were feasible and can be utilized for further research. The “in-presence” EP was only applied to a single AD patient, but a group setting seemed feasible. In online meetings, special group feelings were not perceived by therapists, but patients gave positive feedback.The COVID-19 pandemic meant that substantial modifications of the study methodology were required. Participant recruitment was insufficient despite multiple advertisements. In a former trial including adult AD patients,For larger studies, the authors advise different parallel sessions for each intervention. Finally, the study project could not be performed within the foreseen two-year period and was closed facing renewed research restrictions. From an ethical point of view, results of even few participants should be published to contribute to the scientific evidence. This applies especially for this study, as patients and the study team invested multiple extra efforts.To our knowledge, this was the first study investigating group programs in hypnotherapy, intermittent fasting with diet adjustments, and exercise in AD patients compared with a nonintervention control, gathering experience and first data. Intergroup comparisons could not be performed. However, the use of hypnotherapy in atopic diseases has only been tested in few exploratory studies, and very rarely within the past 20 years.In contrast, and in addition to minor AEs, in this study there was one AE unsurely related to HTP with worsening of symptoms (using a topical immunomodulator). The authors found no other explanation for the individual worsening. However, the possibility of symptom worsening is important for patient information and shared decision-making in hypnotherapy. Delaitre et al performed a retrospective data analysis in 27 AD outpatients (mean age 34.5 years) with symptom persistence despite local AD therapy treated with 2–16 individual hypnotherapy sessions á 20 min. The authors found a reduction in disease severity by EASI (measured by the treating physician) and patients' self-assessments, but reported no AE assessment. They concluded that hypnotherapy might be useful in AD patients.The authors found no further clinical trials in adult AD patients. Although they found the medication regimens comparable between groups, they could not correlate endpoints to medication use, and therefore, they cannot exclude that medication regimens could have influenced the clinical endpoints. The authors can draw no conclusions from the one patient allocated to EP, as outcome changes might be by chance as in prospective case reports.For the first time, group interventions such as HTP, IFDP, and EP were developed for adult AD patients in a university outpatient setting “in-presence” and as online group interventions. The strengths of this study include the implementation of blinded-rated and patient-reported endpoints, and the reporting of mitigations due to the COVID-19 pandemic based on the CONSERVE statement. The main limitations were caused by the COVID-19 pandemic. The change in the trial design (closing one study arm) and the small sample size substantially impair the effectiveness evaluations. However, as this is an exploratory trial, the feasibility of the study interventions could be investigated to a certain extent and the interventions proved practicable, as “in-presence” and as online meetings.Further study limitations include the monocenter setting and the female predominance, which further limits the generalizability of the results. The study design had potential sources of bias: Patients performing HTP, IFDP, or EP received more therapist and/or peer group time and attention than control patients, and blinding of patients and therapists was impossible. Consequently, the observed indications for improvements may have been overestimated. Emerging trends should be verified by confirmatory studies. Further studies should consider to use the subjectively perceived itching intensity (VAS) as a primary endpoint, as this is to patients a meaningful and validated measurement.Even with a modified study design, the study results are meaningful as they provide data and methodology for the group interventions, in presence and online. As patients participated in studies during the COVID-19 pandemic, they think it is ethical to publish the results. They provided an example, how to report a changed study design and results according to the CONSERVE statement.The study results suggest that study interventions are feasible, acceptable, and might be effective, providing justification for the progression to confirmatory clinical studies on the interventions. For larger clinical trials, the authors advise different parallel sessions for each intervention, so that patients can choose convenient timeslots.