Kyrgidis, Athanassios

AbstractIntroductionThe International Hidradenitis Suppurativa Severity Score System (IHS4) is a validated tool that measures inflammatory lesions, including draining tunnels, in hidradenitis suppurativa (HS).ObjectiveTo evaluate secukinumab efficacy using IHS4 in patients with moderate to severe HS.MethodsData from the SUNSHINE and SUNRISE trials, which assessed subcutaneous secukinumab 300 mg every 2 (SECQ2W) and 4 (SECQ4W) weeks in adults with moderate to severe HS, were analyzed. Assessments included changes from baseline in IHS4 and severity classification up to Week 52; IHS4‐55, IHS4‐75, IHS4‐90 responses (55%, 75% and 90% reduction in IHS4) and concordance between IHS4‐55 and HS clinical response (HiSCR), at Weeks 16 and 52.ResultsIn total, 1084 patients (SECQ2W = 361; SECQ4W = 360; placebo = 363) were analyzed. At Week 16, SECQ2W and SECQ4W demonstrated a numerically higher reduction in IHS4 from baseline versus placebo (adjusted mean [95% CI]: −10.80 [−12.30 to −9.30] and −9.46 [−10.96 to −7.96] vs. −4.92 [−6.43 to −3.41]); the reduction was maintained until Week 52 in both dose regimens. A greater proportion of patients achieved IHS4‐55 with SECQ2W (43.4%) and SECQ4W (39.5%) versus placebo (31.5%) at Week 16, with further improvement at Week 52. Similar trends were observed for IHS4‐75 and IHS4‐90 responses. While no patients had mild disease based on IHS4 (80.7% had severe and 19.3% had moderate HS) at baseline, a greater proportion of patients were categorized as having mild disease at Week 16 in the SECQ2W (25.9%) and SECQ4W (24.0%) groups versus placebo (16.4%); this trend continued up to Week 52 in both dose regimens. Strong concordance (>85%) was observed between IHS4‐55 and HiSCR.ConclusionsBoth SECQ2W and SECQ4W demonstrated efficacy in improving treatment response as measured by IHS4 and reducing disease severity versus placebo at Week 16 and these improvements were sustained through Week 52. These findings support that the dynamic and dichotomous IHS4 can efficiently detect treatment response changes in clinical trial settings.Clinical Trials RegistrationSUNSHINE (NCT03713619); SUNRISE (NCT03713632).

Abstract Background Validated, inclusive and easy‐to‐use outcomes for hidradenitis suppurativa are essential both in the clinical trial setting and clinical practice. The continuous IHS4 is a validated tool that dynamically assesses nodules/abscesses/draining tunnels and classifies disease severity as mild/moderate/severe. However, dichotomous outcomes are often required for clinical trials reporting. Objective To develop and validate a dichotomous outcome based on IHS4 that can be used in clinical trial settings and day‐to‐day clinical practice. Methods De‐identified data from the PIONEER‐I and ‐II studies were accessed through Vivli. Potential IHS4 thresholds were analysed using baseline to Week 12 data from adalimumab‐ and placebo‐treated hidradenitis suppurativa patients in the PIONEER‐I trial. The final threshold was chosen based on its ability to discriminate between patients treated with adalimumab or placebo and its association with reduction in inflammatory lesions. The final threshold was validated using data from baseline to Week 12 from adalimumab‐ and placebo‐treated hidradenitis suppurativa patients in both the PIONEER‐II and the combined PIONEER‐I and ‐II studies. Results The best performing cut‐off for the IHS4 was a 55% reduction of the IHS4 score (IHS4‐55). Patients who achieved the IHS4‐55 had an odd's ratio of 2.00 [95%‐CI 1.26–3.18, p = 0.003], 2.79 (95%‐CI 1.76–4.43, p < 0.001) and 2.16 (95%‐CI 1.43–3.29, p < 0.001) for being treated with adalimumab rather than placebo in PIONEER‐I, PIONEER‐II and the combined dataset, respectively. Additionally, the achievement of the IHS4‐55 was associated with a significant reduction in inflammatory nodules, abscesses and draining tunnels in all analysed datasets. Conclusions IHS4‐55, a novel dichotomous IHS4 version, based on a 55% reduction of the total score was developed. The IHS4‐55 performs similarly to the HiSCR in discriminating between adalimumab‐ and placebo‐treated hidradenitis suppurativa patients and shows significant associations with reductions in lesion counts. Moreover, the IHS4‐55 addresses some of the HiSCR drawbacks by dynamically including draining tunnels in a validated manner. By allowing the analysis of hidradenitis suppurativa patients with an abscess and nodule count below 3 but many draining tunnels, this outcome measure will improve inclusivity in clinical trials.

Abstract Objective Behçet's disease ( BD ) is a chronic, relapsing, inflammatory vascular disease with no pathognomonic test. Low sensitivity of the currently applied International Study Group ( ISG ) clinical diagnostic criteria led to their reassessment. Methods An International Team for the Revision of the International Criteria for BD (from 27 countries) submitted data from 2556 clinically diagnosed BD patients and 1163 controls with BD ‐mimicking diseases or presenting at least one major BD sign. These were randomly divided into training and validation sets. Logistic regression, ‘leave‐one‐country‐out’ cross‐validation and clinical judgement were employed to develop new International Criteria for BD ( ICBD ) with the training data. Existing and new criteria were tested for their performance in the validation set. Results For the ICBD , ocular lesions, oral aphthosis and genital aphthosis are each assigned 2 points, while skin lesions, central nervous system involvement and vascular manifestations 1 point each. The pathergy test, when used, was assigned 1 point. A patient scoring ≥4 points is classified as having BD . In the training set, 93.9% sensitivity and 92.1% specificity were assessed compared with 81.2% sensitivity and 95.9% specificity for the ISG criteria. In the validation set, ICBD demonstrated an unbiased estimate of sensitivity of 94.8% (95% CI : 93.4–95.9%), considerably higher than that of the ISG criteria (85.0%). Specificity (90.5%, 95% CI : 87.9–92.8%) was lower than that of the ISG ‐criteria (96.0%), yet still reasonably high. For countries with at least 90%‐of‐cases and controls having a pathergy test, adding 1 point for pathergy test increased the estimate of sensitivity from 95.5% to 98.5%, while barely reducing specificity from 92.1% to 91.6%. Conclusion The new proposed criteria derived from multinational data exhibits much improved sensitivity over the ISG criteria while maintaining reasonable specificity. It is proposed that the ICBD criteria to be adopted both as a guide for diagnosis and classification of BD .