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cons in psoriasis therapy evaluation Dear Editor, Safety and efficacy data rely on two ancillary sources, namely clinical trials and real-world experience. The two sources differ and complement one another in many aspects: for example, the study populations might vary, as the exclusion criteria of clinical trials might not be required in clinical practice. Combining the two might widen the knowledge of safety and efficacy profile from the clinical setting to the everyday practice. In recent years, the therapeutic horizons of psoriasis therapy have been considerably widened by numerous new drugs; the major role has been played by targeted therapies and small molecules. The process of drug approval includes a first phase of clinical trials, where the agent is administered in patients and control groups, and secondly the analysis of trial data by regulatory entities. After the marketing authorization, adverse events related to the drug should be reported to the pharmacovigilance system. However, this postapproval phase only concerns the safety profile, not including efficacy data from real-world experience (RWE). The latest are part of the scientific literature such as case reports, case series, or prospective and retrospective studies implemented by the physicians themselves. Hence both safety and efficacy data rely on two ancillary sources, namely clinical trials and RWE. The two represent a joint resource, as they differ and complement one another in many aspects. First, RWE study population includes a wider range of patients not only in the quantity aspect but also in individuals’ characteristics. Indeed, clinical trials select patients and control groups with specific inclusion and exclusion criteria that restrict the interindividual clinical variability. However, these criteria are mandatory in drugs’ clinical trials in order to avoid possible bias and risks in fragile categories. Thus, RWE extends data in the everyday setting, as physicians deal with more complicated patients (multiple comorbidities, polypharmacy, multifailure subjects) who do not correspond strictly to the patients of clinical trials. In fact, trials inclusion criteria often exclude patients due to their age (e.g., elderly people or children) or comorbidities (e.g., tuberculosis infection, hepatitis B or C). However, in RWE, these conditions do not impede the use of the therapy under discussion, as these do not represent absolute or relative contraindications. RWE can also give additional information on multifailure patients; in fact, the need for a prompt and new available therapy in case of clinical failure is not always compatible with the timing for a complete wash out. Moreover, according to epidemiological data, the RWE population can differ compared to the one of clinical trial, as different subcategories of patients might be more or less represented. For example, although in clinical trials of anti-psoriatic biologic agents elderly patients are not excluded, in RWE they might be more than expected, as population aging is now a global phenomenon. Besides, RWE might include patients with multiple disease and comorbidities, some of which might not have been considered during clinical trials such as other skin or extracutaneous inflammatory or immune diseases. As shown by Kirsten et al., this selection impacts the external validity of benefit–risk ratio; in fact, in clinical trials, exclusion criteria aim to lower the number of patients more prone to adverse events from phase III studies, but on the other hand, they do not ensure a real-life picture. In 2018, Sbidian et al. confirmed this phenomenon in a real-life study; in the 16,545 psoriatic patient cohort, RWE long-term persistence rates of biologic showed lower values compared to the literature data. In clinical practice, biologic-na€ıve subjects had a 3-year persistence rate of 25–30% for anti-tumor necrosis factor alpha (TNF) and 55% for ustekinumab, whereas a rate of 40–60% and 75–80%, respectively, was reported in literature. Nonetheless, data collection in RWE faces other bias; first, it is more difficult to assemble data from RWE in a homogenous manner. Different authors and groups report their experience with different follow-up frequencies, clinical scores, and data shown. Moreover, reports have a fewer number of patients, and not all the investigations taken during the clinical trials are routinely done in clinical practice. In conclusion, it is advisable that RWE and clinical trial data might be joined nowadays, as year by year new drugs are continuously developed and approved for psoriasis. Combining the two sources might widen the knowledge of safety and efficacy profile from the clinical setting to the everyday practice. In fact, since many agents are now available for psoriasis treatment and more patients begin or change biologic every year, RWE represents a valuable tool to integrate clinical data and to develop clinical algorithms for personalized therapeutic approach. Attempts should be taken by both sides of the process to enhance the external validity of safety and efficacy profile; clinical trials should include further details on the patients and reports of single cases with particular clinical conditions, and physicians are encouraged to align data quality and assessment methods for a harmonized scientific literature.