Users of biologics in clinical practice: would they be eligible for phase III clinical studies? Cohort Study in the French Psoriasis Registry PSOBIOTEQ

Abstract

Background Numerous inclusion and exclusion criteria are involved in phase III moderate to severe psoriasis trials investigating the safety and efficacy of biologics. This questions the generalization of results. Methods In this cohort study, we applied inclusion/exclusion criteria for phase III trials from original protocols (adalimumab – REVEAL, ustekinumab – PHOENIX, brodalumab – AMAGINE, secukinumab FIXTURE) to all patients enrolled in the PsoBioTeq prospective registry who received a biological agent for the first time between July 2012 and November 2017. We then compared the efficacy, drug survival and occurrence of adverse events between patients who satisfied/did not satisfy the eligibility criteria for these phase III trials. Results A total of 1267 patients were enrolled, of whom 993 (78.4%) were not eligible for at least one RCT (randomized controlled trial) and 251 (19.1%) did not meet the PASI/PGA severity requirements. Apart from disease severity, the most frequent criteria resulting in exclusion were as follows: non‐plaque psoriasis (12.6%), significant cardiac disease (8.4%), significant liver disease (7.3%), elevated liver enzymes (4.9–9.6%) and personal history of diabetes (9.2%). There was no difference in drug survival between the two groups. The incidence ratio of adverse events was significantly lower in eligible versus non‐eligible patients [0.78 (95% CI 0.62–0.97) (P = 0.03)]. Conclusion The majority of patients treated with biologics in the PsoBioTeq real‐life registry would not have been eligible for phase III moderate to severe psoriasis trials. Patients not eligible for psoriasis phase III clinical trials have a higher incidence of adverse events.

Effectiveness of anti‐interleukin 23 biologic drugs in psoriasis patients who failed anti‐interleukin 17 regimens. A real‐life experience

“…In particular, at baseline, they showed a relative low median PASI value but a high median DLQI and VAS itch scores (Table 1). Basically, the above subjects should not have been eligible for RCT studies since the PASI is too low for them to be enrolled 5‐9 . Also in real‐life studies, patients treated with biologic therapies show PASI values that are generally higher than those recorded in the cohort of patients reported here 10,11 …”

Real‐world efficacy and safety of interleukin‐17 inhibitors for psoriasis: A single‐center experience

“…These patients had a higher risk of severe adverse events than those eligible for randomized controlled trials (RCT). Although there was no difference in the drug survival between patients with psoriasis eligible and ineligible for RCT, the efficacy of anti‐tumor necrosis factor drugs for rheumatoid arthritis was lower in patients ineligible for RCT . Thus, we studied the efficacy, safety and drug survival of IL‐17i in patients with psoriasis treated at Kurume University Hospital.…”

Clinical selection criteria in new clinical trials of hidradenitis suppurativa: External validity and implications on the daily clinical practice

“…In clinical practice, biologic treatments can be used in patients with draining tunnels with low to null AN count 24 . Thus, participants in clinical trials might not be representative of the real‐life HS patients, as happens with psoriatic patients 25,26 . The International Hidradenitis Suppurativa Severity Score System (IHS4) is a newer validated scoring tool to assess HS severity which considers both AN and draining tunnel count 27 .…”

“…24 Thus, participants in clinical trials might not be representative of the real-life HS patients, as happens with psoriatic patients. 25,26 The International Hidradenitis Suppurativa Severity Score System (IHS4) is a newer validated scoring tool to assess HS severity which considers both AN and draining tunnel count. 27 The IHS4 has a complementary role with HiSCR, particularly in the assessment of advanced disease, where the HiSCR may suffer from decreased responsiveness in the presence of low inflammatory nodule counts which can occur in highly cicatricial disease.…”