Background: Guselkumab is an interleukin (IL)‐23 inhibitor with demonstrated efficacy in patients with psoriasis.Objectives: Evaluate the impact of early disease intervention on clinical responses following 28 weeks of guselkumab treatment in patients with moderate‐to‐severe plaque psoriasis. Correlate clinical response and disease duration data with serum biomarker data.Methods: GUIDE is a phase IIIb randomized, double‐blind, parallel‐group, multicentre study of adults with moderate‐to‐severe plaque psoriasis. In study part 1, patients with a short disease duration (SDD [≤2 years]) or a long disease duration (LDD [>2 years]) received guselkumab 100 mg at Week (W) 0, 4, 12, and 20. Those achieving complete skin clearance at W20 and W28 were defined as a super responder (SRe). A multivariable logistic regression analysed the association between baseline factors and the likelihood of becoming an SRe. The relationship between clinical response, disease duration and serum biomarker data was assessed at W0 and 4.Results: In total, 880 patients were enrolled (SDD/LDD = 40.6%/59.4% of patients). More SDD than LDD patients achieved absolute Psoriasis Area and Severity Index (PASI) = 0 at W28 (51.8% vs. 39.4%) and were SRes (43.7% vs. 28.1% [overall 34.4%]). SDD patients also achieved PASI = 0 quicker than LDD patients (median 141 vs. 200 days). Disease duration and prior biologic use had the greatest impact on becoming an SRe, with no strong association among these independent variables. At baseline, there were no significant differences in the serum biomarker levels of IL‐17A, IL‐17F, IL‐22 and β‐defensin 2 between SDD and LDD patients, or between SRe and non‐SRe patients. Guselkumab rapidly decreased these markers of systemic inflammation across all patient groups analysed at W4. Guselkumab was well tolerated.Conclusions: Guselkumab efficacy was consistent across subpopulations, on the skin and systemically. The proportion of SRes was higher in SDD than LDD patients, indicating early treatment intervention may improve clinical outcomes.

Background Significantly more patients with moderate‐to‐severe plaque psoriasis treated with the interleukin (IL)‐17A inhibitor ixekizumab vs. the IL‐23p19 inhibitor guselkumab in the IXORA‐R head‐to‐head trial achieved 100% improvement in Psoriasis Area and Severity Index (PASI 100) at Week 12. Objectives To compare skin and nail clearance and patient‐reported outcomes for ixekizumab vs. guselkumab, up to Week 24. Methods IXORA‐R enrolled adults with moderate‐to‐severe plaque psoriasis (static Physician’s Global Assessment [sPGA] ≥3, PASI ≥12, and BSA ≥10%). Statistical comparisons were performed using the Cochran‐Mantel‐Haenszel test stratified by pooled site. Time‐to‐first‐event comparisons were performed using Kaplan‐Meier analysis, and p values were generated using adjusted log‐rank test stratified by treatment group. Cumulative days at clinical and patient‐reported responses (percentage of the maximum area‐under‐the‐curve times study duration) were compared by ANCOVA. Results Of the 1027 patients randomly assigned, 90% completed the trial (465/520 ixekizumab and 459/507 guselkumab). As early as Week 2 and through Week 16, more patients on ixekizumab achieved PASI 100 (p<0·01). At Week 24, ixekizumab was non‐inferior to guselkumab (50% vs. 52%, difference: ‐2·3%), with no statistically significant difference in PASI 100 (p=0·414). More patients receiving ixekizumab showed completely clear nails at Week 24 (52% vs. 31%; p=0·007). The median time‐to‐first PASI 50/75/90 and PASI 100 were 2 and 7.5 weeks shorter, respectively, for patients on ixekizumab versus guselkumab (p<0·001). Patients on ixekizumab also had a greater cumulative benefit, with more days at PASI 90 and 100, Dermatology Life Quality Index of 0 or 1, and itch‐free (p<0·05). Serious adverse event frequency was 3% for each group with no new safety signals. Conclusions Ixekizumab was non‐inferior to guselkumab in complete skin clearance and superior in clearing nails at Week 24. Ixekizumab cleared skin more rapidly in patients with moderate‐to‐severe plaque psoriasis, with a greater cumulative benefit, than guselkumab. Overall, safety findings were consistent with the known safety profile for ixekizumab.

Background Plaque psoriasis affects children and adults, but treatment options for paediatric psoriasis are limited. Objectives Evaluate the efficacy and safety of ixekizumab (IXE), a high‐affinity monoclonal antibody that selectively targets interleukin‐17A, for moderate‐to‐severe paediatric psoriasis. Methods In a randomised, double‐blind, placebo‐controlled, Phase 3 study (IXORA‐PEDS), patients (age 6 to <18 years) with moderate‐to‐severe plaque psoriasis were randomised 2:1 to weight‐based dosing of IXE every four weeks (IXE Q4W, N=115) or placebo (N=56) through Week 12, followed by open‐label IXE Q4W. Co‐primary endpoints were the proportion of patients at Week 12 achieving ≥75% improvement in the Psoriasis Area and Severity Index (PASI 75) and a static Physician’s Global Assessment score of 0 or 1 (sPGA 0,1). Results IXE was superior (p<0·001) to placebo for both co‐primary endpoints (PASI 75: IXE Q4W, 89%; placebo, 25% and sPGA [0,1]: IXE Q4W, 81%; placebo, 11%) and all gated secondary endpoints, including PASI 75 and sPGA (0,1) at Week 4, improvement in itch, and complete skin clearance. IXE Q4W provided significant (p<0·001) improvements versus placebo in quality of life and clearance of scalp and genital psoriasis. Responses at Week 12 were sustained or further improved through Week 48. Through Week 12, 45% (placebo) and 56% (IXE) of patients reported treatment‐emergent adverse events. One serious adverse event was reported (IXE), one patient discontinued due to an adverse event (placebo), and no deaths were reported. Conclusions IXE was superior to placebo in the treatment of moderate‐to‐severe paediatric psoriasis and the safety profile was generally consistent with that observed in adults.

Background: Nemolizumab is a humanized anti‐IL‐31 receptor blocker in phase 3 for atopic dermatitis (AD).Objective: Analyse onset of action of nemolizumab 30 mg and compare efficacy and safety vs placebo (SC q4wk plus loading dose) in moderate‐to‐severe AD.Methods: Post hoc analysis of patients with Eczema Area and Severity Index (EASI) scores ≥ 16 from a phase 2b trial of moderate‐to‐severe AD. Endpoints were change in EASI score at week 16, peak pruritus numeric rating scale (PP‐NRS), Investigator’s Global Assessment (IGA), changes in sleep and responders with ≥ 4‐point improvement on PP‐NRS.Results: There was a significantly greater itch relief apparent by Day 2 (−22.8% vs –12.3% PP‐NRS; P = 0.005) which continued to improve through week 16 (−68.5% vs −30.9% PP‐NRS; P < 0.001). At week 16, PP‐NRS ≥ 4‐point response of itch was observed in 68.0% nemolizumab vs 15.9% placebo patients (P ≤ 0.001). There was also a rapid improvement of sleep disturbance with nemolizumab 30 mg, with a significant separation from placebo by Day 3 (−26.6% vs –9.0%; P < 0.001) which further improved till week 16 (−76.0% vs −36.5%; P < 0.001). Also for the EASI score a separation between groups in favour of nemolizumab was observed by week 1 (P ≤ 0.001), which increased through week 16 (−68.6% vs. −42.6%; P = 0.002). Finally, the degree of response was greater in nemolizumab‐treated patients; clinically relevant reductions of 75% EASI were observed in 50.0% of nemolizumab patients versus 15.9% of placebo patients, while 90% reductions were reported for 36.0% and 6.8% of patients, respectively (P < 0.001 for both). IGA success (score of 0/1) was 32.0% for nemolizumab vs 6.8% for placebo (P = 0.002).Nemolizumab was safe and well‐tolerated in this population; nasopharyngitis and upper respiratory tract infection were the most common adverse events.Conclusions: Nemolizumab resulted in very rapid, sustained improvements of inflammation, pruritus and sleep in patients with EASI ≥ 16 at baseline.

Background Obesity is a common comorbidity of psoriasis and can attenuate response to biologic treatment. Objectives To investigate the efficacy, safety and tolerability of secukinumab 300 mg every 2 weeks (Q2W) vs. secukinumab 300 mg every 4 weeks (Q4W) in patients with a higher body weight. Methods In this multicentre, double-blind, parallel-group trial, 331 patients with moderate-to-severe chronic plaque psoriasis weighing ≥90 kg were randomised to receive secukinumab 300 mg Q2W or secukinumab 300 mg Q4W. Patients who did not achieve PASI90 at Week 16 on the Q4W regimen were reallocated to remain on the Q4W regimen or up-titrate to Q2W. Results At Week 16, Q2W dosing (N=165) led to significantly higher PASI90 responses vs. Q4W [N=166; 73.2% vs. 55.5%, one-sided p-value=0.0003, odds ratio estimate (95% confidence intervals): 2.3 (1.4, 3.8). At Week 52, higher efficacy responses were maintained in the Q2W arm (N=165) vs. Q4W (N=83); PASI75: 88.9% vs. 74.8%; PASI90: 76.4% vs. 52.4%, PASI100: 46.7% vs. 27.3%; IGA 0/1: 75.9% vs. 55.6% and DLQI 0/1: 66.1% vs. 48.8%. PASI90 non-responders at Week 16 who up-titrated to Q2W (N=31) showed higher efficacy responses at Week 32 (16 weeks post-up-titration, PASI90: 38.7% vs. 16.5%) vs. those who remained on Q4W (N=40). Safety results were comparable across treatment arms and consistent with the established secukinumab safety profile. Conclusions Secukinumab 300 mg Q2W demonstrated superior and sustained efficacy compared with Q4W in moderate-to-severe plaque psoriasis patients weighing ≥90 kg. PASI90 non-responders derived additional benefits from up-titration to a Q2W regimen. (NCT03504852)

Background The efficacy and safety of tralokinumab, a fully human monoclonal antibody that specifically neutralizes interleukin-13, plus topical corticosteroids (TCS) as needed were evaluated over 32 weeks in the phase III ECZTRA 3 trial. Significantly more tralokinumab- versus placebo-treated patients achieved the primary endpoints of Investigator’s Global Assessment (IGA) score of 0/1 and 75% improvement in Eczema Area and Severity Index (EASI-75) and all confirmatory endpoints at Week 16. Objective This post hoc analysis investigated the impact of tralokinumab plus TCS on atopic dermatitis (AD) severity, symptoms, and health-related quality of life (QoL) over the entire 32-week treatment period of ECZTRA 3, including all patients initiated on tralokinumab irrespective of the response achieved at Week 16. Methods Patients were randomized 2:1 to receive subcutaneous tralokinumab 300 mg or placebo every 2 weeks (q2w) with TCS as needed for an initial 16 weeks. At Week 16, patients who achieved the clinical response criteria (IGA 0/1 and/or EASI-75) with tralokinumab were re-randomized 1:1 to tralokinumab q2w or every 4 weeks (q4w), with TCS as needed, for another 16 weeks. Patients not achieving the clinical response criteria with tralokinumab received tralokinumab q2w plus TCS from Week 16. All patients randomized to tralokinumab in the initial treatment period were pooled for this analysis, irrespective of response at Week 16 or dosing regimen beyond Week 16. Results Continued tralokinumab (q2w, N = 164; q4w, N = 69) plus TCS treatment provided progressive improvements from Week 16 onwards in AD signs, with 70.2% (177/252) of patients achieving EASI-75 and 50.4% (127/252) achieving EASI-90 at Week 32. Improvements in patient-reported outcomes were observed within the first few weeks of tralokinumab q2w plus TCS treatment and were sustained throughout the 32-week period. At Week 32, patients initiated on tralokinumab q2w plus TCS achieved a relative improvement versus baseline of 70.8% (standard error (SE), 2.4) in eczema-related sleep interference numeric rating scale (NRS) and 66.8% (SE, 3.1) in Dermatology Life Quality Index (DLQI). Mean TCS use during Weeks 16–32 ranged from 9.2 to 13.6 g (SE, 1.2–2.0) q2w. Most patients (89.9% (222/247)) initiated on tralokinumab q2w plus TCS achieved a meaningful improvement in at least one of the three disease domains, including AD signs (EASI-50), symptoms (pruritus NRS improvement ≥ 3), and QoL (DLQI improvement ≥ 4) at Week 16. Of patients initiated on tralokinumab q2w plus TCS, 53.4% (132/247) achieved a clinically meaningful improvement in all three domains at Week 16 (vs. placebo, 28.5% (35/123); p < 0.001). Conclusions Continued tralokinumab treatment plus TCS as needed provides progressive and sustained improvements in AD signs, symptoms, and health-related QoL over 32 weeks. Clinical trial registration NCT03363854; study start date: 22 February 2018; primary completion date: 8 March 2019; study completion date: 26 September 2019. Infographic Video What is the impact of tralokinumab plus topical corticosteroids in adults with moderate-to-severe atopic dermatitis over 32 weeks? (MP4 216,988 KB)