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Summary: Background: Long‐term efficacy and safety of ixekizumab [160 mg at week 0, then 80 mg every 2 weeks (Q2W) for 12 weeks, followed by every 4 weeks (Q4W) thereafter (i.e. Q2W/Q4W), which is the labelled psoriasis dosing where approved, except in Japan] have been established for the treatment of adults with moderate‐to‐severe plaque psoriasis. However, some patients may benefit from remaining on Q2W dosing beyond 12 weeks. Methods: Among patients who had static Physician's Global Assessment (sPGA) > 1 at week 12, efficacy through week 52 of continuous Q2W dosing in the IXORA‐P study was compared indirectly with Q2W/Q4W in the integrated data from the UNCOVER‐1, UNCOVER‐2 and UNCOVER‐3 studies. The continuous Q4W dose group, which had comparable results across studies, was used as the common comparator. Results: In the IXORA‐P study, among patients with sPGA > 1 at week 12, 64% of patients in the continuous Q2W group achieved sPGA ≤ 1 at week 52, which was statistically significantly higher than the 36% of patients with sPGA > 1 in the Q2W/Q4W group based on the integrated data from the UNCOVER studies (P = 0·0007). There were no clinically meaningful differences in frequencies of safety events between patients with sPGA ≤ 1 and patients with sPGA > 1 at week 12 in the IXORA‐P study. Conclusions: Among patients who did not have clear or almost clear skin at week 12, nearly 30% more patients who were treated continuously with ixekizumab Q2W in IXORA‐P had clear or almost clear skin at week 52 when compared indirectly with those who were treated using the labelled psoriasis dosing in integrated UNCOVER studies. What's already known about this topic? Most patients with moderate‐to‐severe psoriasis who were given the labelled psoriasis dosing of ixekizumab [160‐mg loading dose at week 0, 80 mg every 2 weeks (Q2W) through week 12, and 80 mg every 4 weeks (QW4) thereafter] respond quickly with a high percentage of skin clearance.Additionally, patients who achieve static Physician's Global Assessment (sPGA) ≤ 1 by week 12 tend to maintain this response, even after switching to Q4W. What does this study add? Here, we assessed whether patients with sPGA > 1 at week 12 benefited from receiving more frequent dosing beyond the first 12 weeks.The results showed that Q2W dosing beyond 12 weeks resulted in more patients achieving sPGA ≤ 1 by week 52 than the labelled psoriasis dosing among patients with sPGA > 1 at week 12. Linked Comment: Kim. Br J Dermatol 2020; 183:6. Plain language summary available online Respond to this article [ABSTRACT FROM AUTHOR]

Summary: 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, defined as static Physician's Global Assessment ≥ 3, PASI ≥ 12 and involved body surface area ≥ 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 tests stratified by treatment group. Cumulative days at clinical and patient‐reported responses were compared by ancova. The trial was registered with ClinicalTrials.gov (NCT03573323). Results: Of the 1027 patients randomly assigned, 90% completed the trial (465 of 520 ixekizumab and 459 of 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 noninferior to guselkumab (50% vs. 52%, difference −2·3%), with no statistically significant difference in PASI 100 (P = 0·41). 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 vs. guselkumab (P < 0·001). Patients on ixekizumab also had a greater cumulative benefit, with more days at PASI 90 and 100, with Dermatology Life Quality Index of 0 or 1, and itch free (P < 0·05). The frequency of serious adverse events was 3% for each group, with no new safety signals. Conclusions: Ixekizumab was noninferior 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, the safety findings were consistent with the known safety profile for ixekizumab. What is already known about this topic?Patients with plaque psoriasis desire both high levels of clearance and rapid onset of treatment effects.Ixekizumab is a high‐affinity monoclonal antibody that selectively targets interleukin (IL)‐17A.In the 12‐week report of the IXORA‐R study, ixekizumab demonstrated significantly higher efficacy at early timepoints than the IL‐23p19 inhibitor guselkumab, with more patients achieving 100% improvement in Psoriasis Area and Severity Index (PASI 100) and improved quality of life as early as week 4. What does this study add?Patients on ixekizumab vs. guselkumab achieved similar levels of skin clearance and superior efficacy in the resolution of nail psoriasis at week 24.Patients on ixekizumab vs. guselkumab had a greater cumulative benefit, with more days at PASI 90 and 100, more days when psoriasis did not impact their quality of life, and more itch‐free days.The safety profiles of both drugs were consistent with those in previous studies. Linked Comment: Puig. Br J Dermatol 2021; 184:992–993. [ABSTRACT FROM AUTHOR]

Summary: Background: Chronic psoriasis may require medication adjustments over time. Objectives: To evaluate the efficacy/safety of tildrakizumab in subgroups from the reSURFACE studies (N = 1862) that received continuous dosing, higher/lower dosing, treatment interruption/reinitiation and initiation. Methods: Responders [Psoriasis Area and Severity Index (PASI) ≥ 75%] and partial responders (PASI ≥ 50% to < 75%) in Part 3 of the reSURFACE studies (weeks 28–52 or week 64) who received tildrakizumab 200 mg or 100 mg were rerandomized to the same dosage (T100/T100 or T200/T200), a higher/lower dosage (T100/T200 or T200/T100) or placebo (PBO) (T100/PBO or T200/PBO). Patients receiving PBO who relapsed were reinitiated to tildrakizumab. Etanercept (ETN) week‐28 partial responders and nonresponders (PASI < 50%) received tildrakizumab 200 mg (ETN/T200). Results: Among T100/T100 and T200/T200 week‐28 partial responders, the proportion of patients who achieved as‐observed PASI 75 responses increased over time. Among T100/T200 week‐28 partial responders, PASI 75 responses increased from week 32 (38·5%) to week 52 (63·2%) and remained consistent in T200/T100 week‐28 responders. Among patients who relapsed in the T100/PBO and T200/PBO groups, 86% and 83% of those who reinitiated tildrakizumab achieved PASI 75 by week 64, respectively. Among ETN/T200 week‐28 partial responders, PASI 75 responses (nonresponder imputation) increased from week 32 (24·1%) to week 52 (74·7%). PASI 90, PASI 100 and Physician's Global Assessment responses were consistent with PASI 75 results. Treatment was well tolerated. Conclusions: Patients generally fared well with tildrakizumab maintenance, reinitiation, dose adjustment or initiation. What's already known about this topic? Tildrakizumab demonstrated significant efficacy vs. placebo with a positive safety profile during the first 28 weeks of treatment in two randomized double‐blind trials. What does this study add? Treatment scenarios with tildrakizumab, such as long‐term continuous dosing (up to 64 weeks), treatment interruption/reinitiation and switching from another biologic, can be part of the management of plaque psoriasis with a reasonable expectation of efficacy and tolerability. Plain language summary available online Respond to this article [ABSTRACT FROM AUTHOR]

Summary: Background: ABP 501, a U.S.A. Food and Drug Administration‐ and European Medicines Agency‐approved biosimilar, is highly similar to adalimumab in structure, function and pharmacokinetics. Objectives: To demonstrate similarity in efficacy, safety and immunogenicity of ABP 501 vs. adalimumab for moderate‐to‐severe plaque psoriasis (clinical trial: NCT01970488). Methods: Patients were randomized (1 : 1) to receive ABP 501 or adalimumab 40 mg every 2 weeks for 16 weeks. At week 16, patients with ≥ 50% improvement from baseline in Psoriasis Area and Severity Index (PASI) score were eligible to continue to week 52. Patients receiving ABP 501 continued; adalimumab patients were rerandomized (1 : 1) to continue adalimumab or undergo a single transition to ABP 501. Key efficacy assessments included percentage PASI improvement from baseline, PASI responders and mean change in affected body surface area from baseline to weeks 16, 32 and 50. Safety was monitored via adverse events (AEs) and antidrug antibodies (ADAs) were assessed. Results: A total of 308 patients were rerandomized at week 16 (ABP 501/ABP 501, n = 152; adalimumab/adalimumab, n = 79; adalimumab/ABP 501, n = 77). PASI percentage improvements from baseline were similar across groups for weeks 16, 32 and 50 (range: 85·8–88·2%), with no significant differences detected across groups in percentages of PASI 50, 75, 90 and 100 responders. Changes from baseline in percentage body surface area affected were similar across groups and time points. No new safety signals were detected. AEs were balanced between groups. Percentages of patients with binding and neutralizing ADAs were similar across treatments. Conclusions: ABP 501 and adalimumab have similar clinical efficacy, safety and immunogenicity profiles over 52 weeks, including after single transition, in this patient population. [ABSTRACT FROM AUTHOR]

Summary: Background: The relevance of granulocyte–macrophage colony‐stimulating factor (GM‐CSF) in the management of psoriasis has not been studied previously. GM‐CSF is important in the initiation and maintenance of chronic inflammatory processes. Objectives: To investigate the clinical use of GM‐CSF neutralization by evaluating the efficacy and safety of namilumab (AMG203), a monoclonal antibody GM‐CSF inhibitor, in patients with moderate‐to‐severe plaque psoriasis. Methods: A phase II, multicentre, randomized, double‐blind, placebo‐controlled, parallel‐group, dose‐finding, proof‐of‐concept study (NEPTUNE) was conducted. Four doses of namilumab (20, 50, 80 and 150 mg, via subcutaneous injection) were compared with placebo. Assessment of the primary end point – the proportion of patients achieving ≥ 75% reduction in Psoriasis Area and Severity Index (PASI 75 treatment response) – was performed at week 12. Exploratory investigation at the tissue level was conducted in a subset of the overall study population. The trial was registered with the number NCT02129777. Results: In total, 122 patients were enrolled and 106 (86·9%) completed the double‐blind treatment; 16 (13·1%) prematurely discontinued study medication. Serum concentration–time profiles were as expected for subcutaneous delivery of an IgG1 monoclonal antibody, and exposure increased proportionally with dose elevation. The number of patients showing PASI 75 treatment response at week 12 was low in all groups; no significant difference was recorded in this end point between placebo and any namilumab group. Similar outcomes were recorded for other clinical study end points. Moreover, no significant treatment‐related changes from baseline were observed in laboratory investigations of cell types or subpopulations, or cytokines relevant to inflammatory pathways in psoriasis. Conclusions: GM‐CSF blockade is not critical for suppression of key inflammatory pathways underlying psoriasis. What's already known about this topic? Blockade of granulocyte–macrophage colony‐stimulating factor (GM‐CSF) signalling is effective in rheumatoid arthritis.Potential relevance for psoriasis has been indicated by the presence of GM‐CSF in psoriasis‐related skin blister fluid and the serum of patients with psoriasis, and also by elevated expression in psoriatic skin lesions. What does this study add? This is the first clinical investigation into the efficacy and safety of an anti‐GM‐CSF antibody in plaque psoriasis.This study provides no evidence of benefit for GM‐CSF neutralization in the treatment of plaque psoriasis.Safety profiles were comparable in the placebo and anti‐GM‐CSF treatment groups, and no incidences of pulmonary alveolar proteinosis or clinically significant changes in lung function were recorded throughout the short‐term duration of study treatment.Overall, the findings point to key differences in the role of GM‐CSF in the pathogeneses of psoriasis and rheumatoid arthritis. Linked Comment: Crowley. Br J Dermatol 2019; 180:1286–1287. Plain language summary available online Respond to this article [ABSTRACT FROM AUTHOR]

Background Despite unmet need, 15 years have passed since a topical therapy with a new mechanism of action for atopic dermatitis ( AD) has been approved. Janus kinase ( JAK) inhibitor treatment effect via topical application in patients with AD is unknown. Objectives Tofacitinib, a small-molecule JAK inhibitor, was investigated for the topical treatment of AD. Methods In this 4-week, phase IIa, randomized, double-blind, vehicle-controlled study ( NCT02001181), 69 adults with mild-to-moderate AD were randomized 1:1 to 2% tofacitinib or vehicle ointment twice daily. Percentage change from baseline ( CFB) in Eczema Area and Severity Index ( EASI) score at week 4 was the primary end point. Secondary efficacy end points included percentage CFB in body surface area ( BSA), CFB in EASI Clinical Signs Severity Sum Score, proportion of patients with Physician's Global Assessment ( PGA) response and CFB in patient-reported pruritus. Safety, local tolerability and pharmacokinetics were monitored. Results The mean percentage CFB at week 4 in EASI score was significantly greater ( P < 0·001) for tofacitinib (−81·7%) vs. vehicle (−29·9%). Patients treated with tofacitinib showed significant ( P < 0·001) improvements vs. vehicle across all prespecified efficacy end points and for pruritus at week 4. Significant improvements in EASI, PGA and BSA were observed by week 1 and improvements in pruritus were observed by day 2. Safety/local tolerability were generally similar for both treatments, although more adverse events were observed for vehicle vs. tofacitinib. Conclusions Tofacitinib ointment showed significantly greater efficacy vs. vehicle across end points, with early onset of effect and comparable safety/local tolerability to vehicle. JAK inhibition through topical delivery is potentially a promising therapeutic target for AD. [ABSTRACT FROM AUTHOR]

Summary: Background: Short‐term interleukin‐23p19 inhibition by tildrakizumab improves plaque psoriasis and appears to be well tolerated. Objectives: Safety and tolerability were assessed for up to 64 weeks of tildrakizumab therapy using pooled data from three randomized controlled trials for moderate‐to‐severe psoriasis. Methods: Data pools for the placebo‐controlled (up to 16 weeks) and full trial periods (up to 64 weeks) were analysed (n = 2081). Results: In the placebo‐controlled period, frequencies of treatment‐emergent adverse events (TEAEs; range 47·9–54·0%), serious TEAEs (range 1·4–2·3%), discontinuations due to AEs (range 0·6–1·9%), major adverse cardiovascular events (MACEs; range 0·0–0·1%) and severe infections (range 0·0–0·3%) were comparable between tildrakizumab 100 mg, tildrakizumab 200 mg, placebo and etanercept. In the full trial period, exposure‐adjusted rates (patients per 100 patient‐years) for TEAEs, serious TEAEs and discontinuations due to AEs with tildrakizumab 100 mg and 200 mg were lower than or comparable with the placebo rates, and lower than with etanercept. Exposure‐adjusted rates of MACEs (range 0·0–0·5) and severe infections (range 0·9–2·0) were comparable among groups. No TEAEs of inflammatory bowel disease or suicide were reported. Candida skin infections were infrequent at frequencies of 0·1%, 0·3%, 0·0% and 0·0% for the tildrakizumab 100 mg, tildrakizumab 200 mg, placebo and etanercept groups, respectively, in the placebo‐controlled period, and exposure‐adjusted rates of 0·2, 0·7, 0·0 and 0·0, respectively, in the full trial period. Oral candidiasis was also infrequent. Conclusions: Up to 64 weeks of tildrakizumab was well tolerated, with low rates of serious TEAEs, discontinuations due to AEs, and AEs of clinical interest. [ABSTRACT FROM AUTHOR]

Summary: Background: Ixekizumab is an interleukin‐17A antagonist approved for treatment of moderate‐to‐severe plaque psoriasis with a recommended 160‐mg starting dose, then 80 mg every 2 weeks (Q2W) to week 12, and every 4 weeks (Q4W) thereafter. Objective: To evaluate continuous Q2W dosing over 52 weeks. Methods: In this phase III, multicentre, double‐blinded, parallel‐group trial, three ixekizumab dosing regimens were assessed for efficacy and safety at week 52 in patients with moderate‐to‐severe plaque psoriasis randomized at a 2 : 1 : 1 ratio to continuous Q2W (n = 611), continuous Q4W (n = 310) or dose adjustment per protocol (Q4W/Q2W, n = 306), each with a 160‐mg starting dose. Dose adjustment was determined by predefined criteria to which investigators were blinded; 72 (23?5%) patients in the Q4W/Q2W group adjusted dose. Efficacy outcomes were evaluated using logistic regression. Results: Co‐primary end points were met at week 52: Psoriasis Area and Severity Index 75 responses for Q2W and Q4W dose groups were 85·9% and 79·0%, respectively (P = 0·006), and static patient global assessment 0/1 responses for Q2W and Q4W dose groups were 78·6% and 70·6%, respectively (P = 0·005). Treatment‐emergent and serious adverse events were comparable across dose groups. Conclusions: Ixekizumab Q2W had higher efficacy at week 52 than ixekizumab Q4W, with no increase in safety events. [ABSTRACT FROM AUTHOR]

Background Apremilast, an oral phosphodiesterase 4 inhibitor, regulates immune responses associated with psoriasis. Objectives ESTEEM 2 evaluated the efficacy and safety of apremilast 30 mg twice daily for moderate-to-severe plaque psoriasis. Methods This phase III, double-blind, placebo-controlled trial randomized adults to apremilast or placebo (2 : 1). At week 16, placebo patients switched to apremilast. At week 32, apremilast patients achieving ≥ 50% reduction in Psoriasis Area and Severity Index (PASI 50) were rerandomized (1 : 1) to continue apremilast or receive placebo. Upon loss of 50% of PASI improvement obtained at week 32, patients rerandomized to placebo resumed apremilast. Results The modified intention-to-treat population (full analysis set) included 137 placebo and 274 apremilast patients. At week 16, significantly more apremilast patients achieved PASI 75 (28·8%), PASI 50 (55·5%) and static Physician's Global Assessment score of 0 or 1 (20·4%) vs. placebo (5·8%, 19·7%, 4·4%, respectively; P < 0·001). Most patients rerandomized to apremilast at week 32 had a PASI 50 response at week 52 (80%). Patients treated with apremilast showed significant improvements in quality of life (as assessed by the Dermatology Life Quality Index) and pruritus at week 16 compared with placebo ( P < 0·001). The exposure-adjusted incidence of adverse events did not increase with continued apremilast treatment for up to 52 weeks. The most common adverse events were nausea, diarrhoea, nasopharyngitis and upper respiratory tract infection. Conclusions Apremilast was effective in the treatment of moderate-to-severe plaque psoriasis over 52 weeks. [ABSTRACT FROM AUTHOR]

Background Plaque psoriasis has a relatively high prevalence in adolescence, resulting in a significant impact on quality of life, including social interactions. Objectives The primary objective was to assess the safety of once-daily application of fixed-combination calcipotriol plus betamethasone dipropionate gel in adolescent scalp psoriasis. Assessment of efficacy was a secondary objective. Methods This phase II, multicentre, single-arm, open-label, 8-week trial included patients aged 12-17 years with moderate-to-very severe scalp psoriasis according to Investigator's Global Assessment ( IGA) (≥ 10% of the scalp area affected). Results Seventy-eight patients received treatment. Twenty-seven patients (35%) reported a total of 64 adverse events ( AEs); most were mild (33/64) or moderate (22/64) in severity and there were no serious AEs. No cases of hypercalcaemia were reported, and the mean changes from baseline to end of treatment in albumin-corrected serum calcium (0·00 mmol L−1), 24-h urinary calcium excretion (−0·03 mmol per 24 h) and urinary calcium-to-creatinine ratio (−0·12 mmol g−1) were not considered clinically relevant. At the end of treatment 66 patients (85%) were clear or almost clear according to IGA. There was an 80% improvement in mean Total Sign Score from baseline to end of treatment. In total, at the end of treatment, 87% of patients rated their scalp psoriasis as clear or very mild, and 75 (96%) had no or mild pruritus compared with 14 (18%) at baseline. Conclusions Once-daily calcipotriol plus betamethasone dipropionate gel is well tolerated and efficacious for scalp psoriasis in adolescents. [ABSTRACT FROM AUTHOR]

Background Oral isotretinoin ( ISO) is the gold standard for severe nodular acne. However, as some patients are unwilling or unable to take, or are intolerant to, ISO, other options are needed. Objectives To compare efficacy and safety of oral ISO vs. doxycycline 200 mg plus adapalene 0·1%/benzoyl peroxide 2·5% gel (D+A/ BPO) in severe nodular acne over 20 weeks. Methods This was a multicentre, randomized, controlled, noninferiority investigator-blinded study involving 266 subjects. Results D+A/ BPO showed a significantly earlier onset of action in reducing nodules, papules/pustules and total lesions at week 2. ISO was superior in reducing nodules (95·6% vs. 88·7%), papules/pustules (95·2% vs. 79·6%) and total lesions (92·9% vs. 78·2%; all P < 0·01) at week 20. Half as many subjects for D+A/ BPO compared with ISO had treatment-related, medically relevant adverse events (33 events in 18·0% of subjects vs. 73 in 33·8% of subjects, respectively). D+A/ BPO was noninferior to ISO in the intent-to-treat population [95% confidence interval ( CI) −2·7 to 20·8 ( P = 0·13); 63·9% vs. 54·9% of subjects, respectively] and per-protocol population [95% CI 3·9-28·6 ( P = 0·01); 74·3% vs. 58% of subjects, respectively), based on the composite efficacy/safety end point. Conclusions D+A/ BPO showed a favourable composite efficacy/safety profile compared with ISO. This combination is an alternative to ISO in patients intolerant to, or unable or unwilling to take, oral ISO, and is an option for treatment of severe nodular acne. [ABSTRACT FROM AUTHOR]

Summary: Tildrakizumab 是一种相当新型的药物,称为生物制剂,用于治疗中度至重度牛皮癣。这种药物可以防止体内一种与炎症有关的特定分子的活动,这种分子被称为细胞因子白细胞介素 (IL)‐23p19。 先前的研究表明,它优于安慰剂(一种非活性物质,像"糖丸"一样)和一种旧的生物制剂,即 TNF 抑制剂 Etanercept。然而,试验很少反映出现实世界的经历,患者可能会从一种药物换到另一种药物,改变药物剂量或中断治疗,例如因为感染而这样做。 作者(位于美国、加拿大和德国)回顾了两项研究的结果,一项是将两种不同剂量的 Tildrakizumab(每天 100 mg 或 200 mg)与安慰剂进行比较,另一项是将其与 Etanercept 进行比较,其中纳入总共 1862 名患有中度到重度斑块型银屑病的成年患者。 在研究过程中,重新随机分配治疗。他们发现,对 Tildrakizumab 的应答是持续的(这意味着它持续起作用),没有出现一些使用 Etanercept 的患者中出现的继发性失败(在最初满意的应答后对药物的应答性下降),并且在治疗中断后,重新使用药物仍能有效地控制银屑病。总体而言,该药物耐受性良好,这意味着其副作用很小。 本摘要涉及研究:在持续给药、治疗中断、剂量调整和从 Etanercept 转换过来的情况下 Tildrakizumab 治疗斑块型银屑病的有效性和安全性: 来自 III 期研究的结果。 Linked Article: Kimball et al. Br J Dermatol 2020; 182:1359–1368 [ABSTRACT FROM AUTHOR]

Summary: Tildrakizumab is a fairly new type of medicine called a biologic, used for the treatment of moderate‐to‐severe psoriasis. The drug prevents the action of a specific molecule in the body involved in inflammation, known as cytokine interleukin (IL)‐23p19. Previous studies have shown it to be superior to a placebo (an inactive substance, like a "sugar pill") and to an older biologic drug, the TNF inhibitor etanercept. However, trials rarely reflect real‐world experience, where patients may switch from one drug to another, change drug dosage or interrupt treatment, e.g. because of an infection. The authors, based in U.S.A., Canada and Germany, reviewed results from two studies, one comparing two different doses of tildrakizumab (100mg or 200mg per day) with placebo, and the other comparing it with etanercept, including a total of 1862 adults with moderate‐to‐severe plaque psoriasis. Treatments were re‐randomised during the course of the study. They found that the response to tildrakizumab was sustained (meaning it kept working), without the secondary failure (decreasing responsiveness to a drug after an initial satisfactory response) seen in some patients on etanercept, and the drug regained effective control of the psoriasis after treatment was interrupted. Overall the drug was well tolerated, meaning that side effects were minimal. This is a summary of the study: Efficacy and safety of tildrakizumab for plaque psoriasis with continuous dosing, treatment interruption, dose adjustments and switching from etanercept: results from phase III studies Linked Article: Kimball et al. Br J Dermatol 2020; 182:1359–1368 [ABSTRACT FROM AUTHOR]

Linked Article: Papp et al. Br J Dermatol 2019; 180:1352–1360 [ABSTRACT FROM AUTHOR]

Summary: Psoriasis is a long‐lasting disease involving inflammation of the skin. In the most common form of this disease ‐ plaque psoriasis ‐ the inflammation is visible as raised, reddened and often scaly areas which may extend widely over the body. Although not generally a life‐threatening condition, psoriasis may increase the risk of other serious disorders (such as cardiovascular disease), and often leads to much reduced quality of life for patients ‐ through physical discomfort (itching, pain), disability, and related emotional trauma. Furthermore, psoriasis occurs worldwide (affecting up to 3% of the populations in various countries) and cannot be completely cured by available treatments. Together, these issues make the disease a serious global burden. Granulocyte‐Macrophage Colony‐Stimulating Factor (GM‐CSF) is made in the body and is important in controlling functions of the body's immune system and the processes involved in inflammation. Therefore, this study was carried out to establish whether blocking the activities of GM‐CSF in patients with moderate or severe plaque psoriasis could result in significant improvement of the disease. In total, 122 patients were enrolled from Canada, Denmark, Germany, Latvia and Poland. The patients were treated over 10 weeks either with namilumab (GM‐CSF blocker) or a placebo (inactive): assessments of their psoriasis were made during this period, and completed after an additional 2 weeks. Notably, throughout the 12‐week study duration no significant improvement was detected for namilumab‐treated patients ‐ in marked contrast to treatment benefit found in a similar study involving patients with rheumatoid arthritis. These findings point to different roles for GM‐CSF in the two diseases, and suggest that blocking GM‐CSF activity alone is not enough for effective treatment of plaque psoriasis. Linked Article: Papp et al. Br J Dermatol 2019; 180:1352–1360 [ABSTRACT FROM AUTHOR]

Atopic dermatitis has a well-known association with mental health comorbidities. This article reviews the mental health interventions currently available to patients and caregivers, including the use of multidisciplinary clinics and peer support programmes. Future research is needed to understand the efficacy of these interventions, the optimal formats and the accessibility of mental health resources. Atopic dermatitis (AD) is associated with high levels of psychosocial burden, often resulting in poor mental health outcomes. Despite this association, few studies have evaluated the efficacy of mental health interventions within this population. Utilization of multidisciplinary and peer-led support, in addition to equipping patients with psychological tools, may be beneficial in improving mental health outcomes. Future research is needed to determine which interventions and formats are desired by, effective in and accessible to patients and caregivers with AD. [ABSTRACT FROM AUTHOR]

Janus kinase (JAK) refers to a family of tyrosine kinases that are involved in the production of proinflammatory mediators in response to various extracellular signals. The JAK–signal transducer and activator of transcription (STAT) pathway is an appealing target in many inflammatory illnesses as this pathway modulates immune cell activation and T-cell-mediated inflammation in response to several cytokines. The practical considerations of prescription for topical and oral JAK inhibitors (JAKis) in atopic dermatitis, vitiligo and psoriasis have been covered in prior publications. Currently, the US Food and Drug Administration has approved the topical JAKi ruxolitinib for atopic dermatitis and nonsegmental vitiligo. None of the remaining first- or second-generation topical JAKis have been approved for topical application in any dermatological indications so far. For this review, the PubMed database was searched using 'topical' and 'JAK inhibitor' or 'Janus kinase inhibitor' or the names of individual drug molecules as the keyword in the title with no date limits. The description of topical JAKi usage in dermatology from the literature was evaluated in each abstract. The current review concentrates on emphasizing the rising use of topical JAKis in both approved and off-label dermatological applications for both old and novel conditions. Currently, the Food and Drug Administration has approved the topical Janus kinase inhibitor (JAKi) ruxolitinib for atopic dermatitis and nonsegmental vitiligo. None of the remaining first- or second-generation topical JAKis have been approved for topical application in any dermatological indications so far. The current review concentrates on emphasizing the rising use of topical JAKis in both approved and off-label dermatological applications for both old and novel conditions. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) in people with skin of colour can appear psoriasiform, lichenoid, scaly or papular, with a violaceous colour and there is a higher prevalence of post-inflammatory dyspigmentation compared with affected individuals of White ethnicities, which can limit the use of current severity assessment tools. Greater participation from patients of different ethnicities in clinical trials is needed; with adequate representation, future studies may be able to better characterize potential differences in AD between different ethnic groups, as well as differences in treatment response. Recent advances in atopic dermatitis (AD) present the condition as a heterogeneous disease of distinct endotypes across ethnic groups. AD in people with skin of colour may appear psoriasiform, lichenoid, scaly or papular, with a violaceous colour and there is a higher prevalence of post-inflammatory dyspigmentation compared with affected individuals of White ethnicity. These differences in clinical presentation may limit the use of AD assessment tools in people with skin of colour, leading to the potential for misdiagnosis and underestimation of severity, particularly in relation to assessment of erythema. Recent targeted therapies for AD have been studied in multiple ethnic groups; however, ethnicity-based subgroup analysis is often not performed. Further research is required to understand whether treatment responses or safety may differ among ethnic groups. [ABSTRACT FROM AUTHOR]

Background Scalp psoriasis affects most patients with psoriasis, but it can be difficult to treat. Objectives To evaluate the efficacy and safety of once-daily roflumilast foam 0.3% on scalp and body psoriasis. Methods In a phase IIb randomized controlled trial, adults and adolescents aged ≥ 12 years with scalp and body psoriasis were randomized (2 : 1) to roflumilast foam 0.3% or vehicle for 8 weeks. The primary efficacy endpoint was scalp Investigator Global Assessment (S-IGA) success (score of 'clear' or 'almost clear' plus ≥ 2-grade improvement from baseline) at week 8. Safety and tolerability were also evaluated. Results Significantly more roflumilast-treated patients (59.1%) than vehicle-treated patients (11.4%) achieved S-IGA success at week 8 (P < 0.001); differences favoured roflumilast as early as the first postbaseline visit at week 2 (P < 0.001). Significant improvements were also seen for secondary endpoints, including body IGA success, Scalp Itch Numeric Rating Scale and the Psoriasis Scalp Severity Index. The safety of roflumilast was generally similar to vehicle. Patients treated with roflumilast experienced low rates of treatment-emergent adverse events (AEs), with few discontinuations due to an AE. Few patients with skin of colour (11%) and few adolescents (0.7%) were included. Conclusions The results support the further development of roflumilast foam for treating scalp and body psoriasis. [ABSTRACT FROM AUTHOR]

Background Limited data are available regarding patient-centred dosing of dupilumab for atopic dermatitis (AD) in daily practice. Objectives To evaluate our patient-centred dupilumab dosing regimen in daily practice, to assess prognostic factors for successful tapering and to estimate medication-related cost savings. Methods This prospective multicentre study included adult patients with AD, participating in the BioDay registry, treated with dupilumab for ≥ 1.3 years. Interval prolongation was considered in the case of dupilumab standard dose for ≥ 1 year and persistent controlled AD [Eczema Area and Severity Index (EASI) ≤ 7; ≥ 6 months]. Primary endpoints were the mean EASI and Numeric Rating Scale (NRS)-pruritus after the start of tapering. Prognostic factors for successful tapering were analysed with logistic regression and a cost-savings analysis was performed. Results A total of 595 patients were included, of whom 401 patients [mean EASI 2.5 (SD 2.3); NRS-pruritus of 2.4 (SD 1.9) at the start of tapering] prolonged their dupilumab interval. In 83.3% of these patients tapering was successful; most patients used dupilumab every 3 or 4 weeks (Q3W/Q4W). A significant small increase was observed for EASI (highest mean 3.5) and NRS-pruritus (highest mean 3.2) (P < 0.001); however, scores remained low. Predicting successful tapering showed nonsignificant odds ratios for all incorporated variables. The estimated cost savings was €3 977 033.98 for 401 patients between January 2019 and June 2022. Conclusions This study showed successful tapering of dupilumab in 83.3% of patients with AD who attempted tapering, while maintaining controlled disease and with the majority using Q3W/Q4W. Interval prolongation can be beneficial both for the patient and from a socio-economic perspective. [ABSTRACT FROM AUTHOR]

Background Almost 50% of patients with skin psoriasis have concomitant nail involvement. The comparative effectiveness of the available biologics for nail psoriasis (NP) is still an area of contention because of limited data on nails. Objectives We conducted a systematic review and network meta-analysis (NMA) to compare the efficacy of biologics in achieving complete resolution of NP. Methods We identified studies in PubMed, EMBASE and Scopus. The eligibility criteria included randomized controlled trial (RCTs) or cohort studies for psoriasis or psoriatic arthritis with at least two arms of active comparator of biologic reporting at least one efficacy outcome of interest: that is the Nail Psoriasis Severity Index (NAPSI), the modified NAPSI or the Physician's Global Assessment of Fingernail Psoriasis with a score of 0. Results Fourteen studies comprising seven treatments met the inclusion criteria, and were included in the NMA. The NMA showed the odds of complete NP resolution were superior with ixekizumab [risk ratio (RR) 1.4, 95% confidence interval (CI) 0.73–3.10] compared with the treatment of reference (adalimumab). Brodalumab (RR 0.92, 95% CI 0.14–7.40), guselkumab (RR 0.81, 95% CI 0.40–1.80), infliximab (RR 0.90, 95% CI 0.19–4.60) and ustekinumab (RR 0.33, 95% CI 0.08–1.60) demonstrated worse therapeutic effect compared with adalimumab. According to the surface under the cumulative ranking curve, ixekizumab 80 mg every 4 weeks had the highest probability of being the best treatment. Conclusions The interleukin-17A inhibitor ixekizumab has the highest rate of complete nail clearance and it can be considered the best-ranked therapy from the present evidence. This study is relevant to daily practice as it facilitates the decision when choosing between the wide variety of available biologics in patients for whom clearance of nail symptoms is the first concern. [ABSTRACT FROM AUTHOR]

Background Generalized pustular psoriasis (GPP) is a systemic inflammatory disease that can be severe, debilitating and life threatening. Uncontrolled activation of interleukin (IL)-36 proinflammatory activity may underlie the pathogenesis of GPP. Currently, GPP-specific treatment options are limited. Objectives To evaluate the efficacy and safety of the anti-IL-36 receptor antibody imsidolimab in patients with GPP. Methods In an open-label, single-arm, multiple-dose study, patients with GPP were treated with imsidolimab to assess clinical efficacy, tolerability and safety. Patients received an intravenous dose of imsidolimab 750 mg on day 1, followed by three subcutaneous doses of imsidolimab 100 mg administered on days 29, 57 and 85. The primary efficacy endpoint was the proportion of patients who achieved a clinical response at weeks 4 and 16 following treatment with imsidolimab, as measured by the Clinical Global Impression scale. Results Eight patients were enrolled and six completed the study. Responses were observed as early as day 3, most rapidly for pustulation relative to other manifestations of GPP, with continued and consistent improvement across multiple efficacy assessments at day 8, day 29 and through day 113. Most treatment-emergent adverse events (TEAEs) were mild to moderate in severity. No patient discontinued the study owing to a nonserious TEAE. Two patients experienced serious adverse events (SAEs); no deaths were reported. Conclusions Imsidolimab demonstrated a rapid and sustained resolution of symptoms and pustular eruptions in patients with GPP. It was generally well tolerated, with an acceptable safety profile, and is advancing to phase III trials. These data support the targeting of IL-36 signalling with a specific antibody – imsidolimab – as a therapeutic option for this severely debilitating condition. [ABSTRACT FROM AUTHOR]

Background Plaque psoriasis (PsO) is an inflammatory skin disease driven, in part, by the activation of Janus kinase (JAK) signalling pathways. Objectives To assess the efficacy and safety of multiple doses of topical brepocitinib, a tyrosine kinase 2/JAK1 inhibitor, in participants with mild-to-moderate PsO. Methods This phase IIb multicentre randomized double-blind study was conducted in two stages. In stage 1, participants received one of eight treatments for 12 weeks: brepocitinib 0.1% once daily, 0.3% once or twice daily, 1.0% once or twice daily, 3.0% once daily, or vehicle once or twice daily. In stage 2, participants received brepocitinib 3.0% twice daily or vehicle twice daily. The primary endpoint was the change from baseline in Psoriasis Area and Severity Index (PASI) score at week 12, analysed using analysis of covariance. The key secondary endpoint was the proportion of participants who achieved a Physician Global Assessment response [score of clear (0) or almost clear (1) and an improvement of ≥ 2 points from baseline] at week 12. Additional secondary endpoints included the difference vs. vehicle in change from baseline in PASI, using mixed-model repeated measures, and the change from baseline in Peak Pruritus Numerical Rating Scale at week 12. Safety was monitored. Results Overall, 344 participants were randomized. Topical brepocitinib did not result in statistically significant changes compared with respective vehicle controls in the primary or key secondary efficacy endpoints for any dose group. At week 12, least squares mean change from baseline in PASI score ranged from –1.4 to –2.4 for the brepocitinib once-daily groups vs. –1.6 for vehicle once daily, and from –2.5 to –3.0 for the brepocitinib twice-daily groups vs. –2.2 for vehicle twice daily. From week 8, change from baseline in PASI score separated from vehicle in all brepocitinib twice daily groups. Brepocitinib was well tolerated, with adverse events (AEs) occurring at similar rates across groups. One participant in the brepocitinib 1.0% once-daily group developed a treatment-related AE of herpes zoster in the neck area. Conclusions Topical brepocitinib was well tolerated but did not result in statistically significant changes compared with vehicle when administered at the doses evaluated to treat signs and symptoms of mild-to-moderate PsO. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is a common inflammatory skin disease characterized by scaly, oozing skin and itch. In moderate-to-severe AD, treatment options have been historically very limited and off-label use has been a common method for disease management. For decades, ciclosporin A was the only systemic immunosuppressive drug approved in most European countries to address this major unmet medical need. However, increased understanding of the pathophysiology of AD has led to a revolution in the treatment of this potentially debilitating disease. Following the approval of the first biological therapy for AD in 2017, there has been a rapid expansion of compounds under development and four additional systemic therapies have been approved in Europe and the USA within the past 3 years alone. In this review, we underscore how key breakthroughs have transformed the therapeutic landscape of AD, leading to a major expansion of type 2 immunity-targeted biological therapies, exploration of neuroimmune modulatory agents, and interest in Janus kinase inhibition. [ABSTRACT FROM AUTHOR]

Objective PsA is a chronic disease with heterogeneous clinical manifestations requiring treatment options with long-term efficacy and safety. In this follow-up analysis, the 52-week efficacy and safety of risankizumab 150 mg in patients with active PsA who had previous inadequate response/intolerance to one or more conventional synthetic DMARDs (csDMARD-IR) were evaluated. Methods KEEPsAKE 1 is an ongoing, global, phase 3 study with a 24-week, double-blind, placebo-controlled period (period 1) and an open-label extension period (period 2). In period 1, eligible patients were randomized 1:1 to receive subcutaneous risankizumab 150 mg or placebo at weeks 0, 4 and 16. At week 24 (period 2), all continuing patients received open-label risankizumab 150 mg every 12 weeks through week 208. Results At week 24, 57.3% of risankizumab-treated patients (n  =   483) achieved ≥20% improvement in ACR criteria (ACR20) vs 33.5% of placebo-treated patients (n  =   481; P  < 0.001). At week 52, 70.0% of patients who were randomized to receive continuous risankizumab therapy and 63.0% of patients who were randomized to receive placebo in period 1 and then receive risankizumab at week 24 achieved ACR20. Similar result trends were observed for other efficacy measures. Risankizumab was well tolerated through 52 weeks of treatment with a consistent safety profile from week 24 through week 52. Conclusion In patients with active PsA who were csDMARD-IR, continuous risankizumab treatment demonstrated robust long-term efficacy and was well tolerated through 52 weeks of treatment. Trial registration ClinicalTrials.gov, http://clinicaltrials.gov , KEEPsAKE1, NCT03675308. [ABSTRACT FROM AUTHOR]

Objective PsA is a chronic inflammatory disease in which the skin and joints are affected. In this follow-up analysis, the 52-week efficacy and safety of risankizumab 150 mg in patients with active PsA who had previous inadequate response/intolerance to one or two biologic therapies (Bio-IR) or one or more conventional synthetic DMARDs (csDMARD-IR) were evaluated. Methods In the ongoing, phase 3, KEEPsAKE 2 trial, patients with active PsA were randomized 1:1 to receive subcutaneous risankizumab 150 mg or placebo at weeks 0, 4 and 16 (period 1). At week 24 (period 2), patients who received placebo were switched to risankizumab, and all patients received risankizumab 150 mg every 12 weeks from weeks 28 to 208. Results At week 24, 51.3% of risankizumab-treated patients (n  =   224) achieved ≥20% improvement in ACR criteria (ACR 20) vs 26.5% of placebo-treated patients (n  =   220; P  <   0.001). At week 52, 58.5% of patients randomized to receive continuous risankizumab achieved ACR20, and 55.7% of patients who switched from placebo to risankizumab at week 24 achieved ACR20. Similar trends were observed for other efficacy measures. Rates of serious treatment-emergent adverse events (TEAEs) and TEAEs leading to discontinuation remained stable through week 52, and no deaths were reported. Conclusion Risankizumab was well tolerated and improved symptoms of PsA in Bio-IR/csDMARD-IR patients, with a consistent long-term safety profile from weeks 24 to 52. Trial registration United States National Library of Medicine clinical trials database www.clinicaltrials.gov ; KEEPsAKE 2; NCT03671148. [ABSTRACT FROM AUTHOR]

Background Evidence suggests an association between atopic eczema (AE) or psoriasis and mental illness; however, the factors associated with mental illness are unclear. Objectives To synthesize and evaluate all available evidence on factors associated with depression, anxiety and severe mental illness (SMI) among adults with AE or psoriasis. Methods We searched electronic databases, grey literature databases and clinical trial registries from inception to February 2022 for studies of adults with AE or psoriasis. Eligible studies included randomized controlled trials (RCTs), cohort, cross-sectional or case–control studies where effect estimates of factors associated with depression, anxiety or SMI were reported. We did not apply language or geographical restrictions. We assessed risk of bias using the Quality in Prognosis Studies tool. We synthesized results narratively, and if at least two studies were sufficiently homogeneous, we pooled effect estimates in a random effects meta-analysis. Results We included 21 studies (11 observational, 10 RCTs). No observational studies in AE fulfilled our eligibility criteria. Observational studies in people with psoriasis mostly investigated factors associated with depression or anxiety – one cross-sectional study investigated factors associated with schizophrenia. Pooled effect estimates suggest that female sex and psoriatic arthritis were associated with depression [female sex: odds ratio (OR) 1.62, 95% confidence interval (CI) 1.09–2.40, 95% prediction intervals (PIs) 0.62–4.23, I 2 = 24.90%, τ 2 = 0.05; psoriatic arthritis: OR 2.26, 95% CI 1.56–3.25, 95% PI 0.21–24.23, I 2 = 0.00%, τ 2 = 0.00] and anxiety (female sex: OR 2.59, 95% CI 1.32–5.07, 95% PI 0.00–3956.27, I 2 = 61.90%, τ 2 = 0.22; psoriatic arthritis: OR 1.98, 95% CI 1.33–2.94, I 2 = 0.00%, τ 2 = 0.00). Moderate/severe psoriasis was associated with anxiety (OR 1.14, 95% CI 1.05–1.25, I 2 0.00%, τ 2 = 0.00), but not depression. Evidence from RCTs suggested that adults with AE or psoriasis given placebo had higher depression and anxiety scores compared with comparators given targeted treatment (e.g. biologic agents). Conclusions Our review highlights limited existing research on factors associated with depression, anxiety and SMI in adults with AE or psoriasis. Observational evidence on factors associated with depression or anxiety in people with psoriasis was conflicting or from single studies, but some identified factors were consistent with those in the general population. Evidence on factors associated with SMIs in people with AE or psoriasis was particularly limited. Evidence from RCTs suggested that AE and psoriasis treated with placebo was associated with higher depression and anxiety scores compared with skin disease treated with targeted therapy; however, follow-up was limited. Therefore, long-term effects on mental health are unclear. [ABSTRACT FROM AUTHOR]

Background: In the long-term extension study of the ERASURE and FIXTURE trials, the efficacy of secukinumab (a fully human anti-interleukin-17A monoclonal antibody) was demonstrated to have been maintained through to year 3 of treatment in moderate-to-severe plaque psoriasis. Objectives: To assess the efficacy and safety of secukinumab through to year 5 of treatment in moderate-to-severe plaque psoriasis. Methods: Responders with ≥ 75% improvement in Psoriasis Area and Severity Index (PASI 75) from two core trials – ERASURE and FIXTURE – were randomized 2 : 1 at year 1 (end of core trials) to either the same dose (300 or 150 mg, continuous treatment) or placebo (treatment withdrawal) every 4 weeks, until year 3 or relapse (> 50% reduction in maximal PASI from core study baseline). Partial responders (achieving PASI 50 but not PASI 75) at year 1 continued at the same dose as in the core trials. At year 3, all patients received open-label secukinumab treatment, with those on secukinumab 300 mg continuing on their dose, while those on secukinumab 150 mg or placebo received secukinumab 150 or 300 mg based on the physician's discretion. The study is registered on ClinicalTrials.gov with the identifier NCT01544595. Results: Most patients randomized to placebo at year 1 relapsed, but the response was rapidly recaptured upon reinitiation of treatment. PASI responses were sustained with secukinumab through to year 5. The PASI responses for the 300 mg responders + partial responders group at year 1 (PASI 75/90/100: 86.8%/72.8%/45.9%) trended downwards until year 3 (PASI 75/90/100: 82.3%/58.4%/32.7%) and then remained stable through year 4 (PASI 75/90/100: 83.3%/60.1%/32.2%) until year 5 (PASI 75/90/100: 81.1%/62.8%/35.1%). Dermatology Life Quality Index showed sustained benefit up to year 5. Absolute PASI responses were maintained throughout the study. The most common adverse events (AEs) were infections and infestations, nasopharyngitis, and upper respiratory tract infections (URTIs). The overall exposure-adjusted incidence rate (EAIR; with 95% confidence interval) for all AEs was 139.9 (130.3–149.9). EAIRs for Crohn's disease and neutropenia were 0.1 (0.0–0.3) and 0.5 (0.3–0.8), respectively. Conclusions: The 4-year extension of two pivotal phase III trials demonstrated that secukinumab treatment was effective through to year 5 and improved quality of life in patients with moderate-to-severe plaque psoriasis. The most common AEs were infections and infestations, nasopharyngitis, and URTIs. The safety profile was consistent with that in the secukinumab phase II/III clinical development programme. Treatment with secukinumab in the 4-year extension study (i.e. through to Year 5) of two pivotal Phase III trials (ERASURE and FIXTURE trials), demonstrated efficacy through to Year 5 and improved the quality of life of patients with moderate to severe psoriasis. The safety profile of secukinumab was consistent with that in the secukinumab Phase II/III clinical development program." cd_value_code="text"/> [ABSTRACT FROM AUTHOR]

Objectives PsA is a heterogeneous disease that impacts many aspects of social and mental life, including quality of life. Risankizumab, an antagonist specific for IL-23, is currently under investigation for the treatment of adults with active PsA. This study evaluated the impact of risankizumab vs placebo on health-related quality of life (HRQoL) and other patient-reported outcomes (PROs) among patients with active PsA and inadequate response or intolerance to conventional synthetic DMARD (csDMARD-IR) in the KEEPsAKE 1 trial. Methods Adult patients with active PsA (n  = 964) were randomized (1:1) to receive risankizumab 150 mg or placebo. PROs assessed included the 36-Item Short-Form Health Survey (SF-36, v2), Functional Assessment of Chronic Illness Therapy–Fatigue (FACIT-Fatigue), EuroQoL-5 Dimension-5 Level (EQ-5D-5L), Patient's Assessment of Pain, Patient's Global Assessment (PtGA) of Disease Activity, and Work Productivity and Activity Impairment–PsA (WPAI-PsA) questionnaire. Least squares (LS) mean change from baseline at week 24 was compared between risankizumab and placebo. Results At week 24, differences between groups were observed using LS mean changes from baseline in SF-36 physical component summary and mental component summary; FACIT-Fatigue; EQ-5D-5L; Patient's Assessment of Pain; PtGA; all eight SF-36 domains (all nominal P  < 0.001); and the WPAI-PsA domains of impairment while working (presenteeism), overall work impairment and activity impairment (all nominal P  < 0.01). Conclusion Risankizumab treatment resulted in greater improvements in HRQoL, fatigue, pain and work productivity in patients with active PsA who have csDMARD-IR, when compared with placebo. Trial registration ClinicalTrials.gov, https://clinicaltrials.gov , NCT03675308 [ABSTRACT FROM AUTHOR]

Background BE SURE 1-year results demonstrated the superior efficacy of bimekizumab compared with adalimumab with no unexpected safety findings. Objectives To provide efficacy and safety data over 2 years of bimekizumab treatment compared with adalimumab from BE SURE and the BE BRIGHT open-label extension (OLE) in patients with moderate-to-severe plaque psoriasis. Methods The 56-week double-blinded BE SURE phase III randomized controlled trial randomized patients 1 : 1 : 1 to bimekizumab 320 mg every 4 weeks (Q4W), bimekizumab 320 mg Q4W to week 16 then every 8 weeks (Q8W), or adalimumab 40 mg every 2 weeks to week 24 then bimekizumab 320 mg Q4W. After completing BE SURE, patients could enter the ongoing BE BRIGHT OLE, with possible dosing adjustments based on Psoriasis Area and Severity Index (PASI). The primary outcome in BE BRIGHT was incidence of treatment-emergent adverse events (TEAEs); safety data are reported by study period through week 104. Efficacy data are reported for the intention-to-treat population through week 104 by initial randomization group, with ≥ 90% improvement from baseline PASI (PASI 90) and 100% improvement (PASI 100) as key outcomes. Results Of the patients randomized to bimekizumab, 158 were assigned to Q4W, and 161 to Q4W/Q8W. At week 104, PASI 90 was achieved by 91.2% and 89.7%, and PASI 100 was achieved by 72.3% and 68.1%, for Q4W and Q4W/Q8W, respectively; comparable to week 16 results. Among the 159 patients randomized to adalimumab, responses rapidly and substantially increased after the week 24 bimekizumab switch; at week 104, 96.9% and 70.2% of patients achieved PASI 90 and PASI 100 respectively. Through weeks 24–104, the three most common TEAEs in any bimekizumab-treated group were nasopharyngitis, oral candidiasis and upper respiratory tract infection. Rates of serious TEAEs were low. Conclusions Clinical responses observed through week 16 of BE SURE in patients randomized to bimekizumab were sustained through 104 weeks of treatment, regardless of Q4W or Q8W maintenance dosing. Response rates were also sustained through week 104 in patients who switched from adalimumab to bimekizumab at week 24, and were similar to those observed in the bimekizumab groups. Bimekizumab was well tolerated with no new safety signals. [ABSTRACT FROM AUTHOR]

Background: Patient adherence to topical antipsoriatic drugs is often poor, leading to poor efficacy. Use of long‐term support delivered by dermatological nurses to patients treated with topical drugs may improve outcome. Aim: To evaluate whether regular support from dermatological nurses improves outcome and treatment adherence in patients with psoriasis receiving topical medications. Methods: We conducted a randomized controlled trial (RCT) (clinicaltrials.gov registration NCT04220554), in which patients received once‐daily topical medications (containing corticosteroids and/or calcipotriol) for as long as their psoriasis was visible. The patients were randomly allocated to standard care by the dermatologist either with (n = 51) or without (n = 52) support from dermatological nurses. The nurse support intervention consisted of a structured dermatological consultation at baseline and Week 1, followed by contact with a nurse each month (in the outpatient clinic or by telephone). The primary outcome was severity of psoriasis, which was measured by the Lattice System Physician's Global Assessment (LS‐PGA) and assessed by intention‐to‐treat analyses using linear mixed regression models for longitudinal data. Secondary outcomes were quality of life (measured by the Dermatology Life Quality Index; DLQI) and good adherence (defined as use of ≥ 80% of recommended doses). Results: In total, 92 patients (89%) completed the 48‐week trial period. The intervention group improved more than the nonintervention group from baseline to Week 24 in LS‐PGA (2.21 vs. 1.28, P = 0.001) and in DLQI at Week 12 (6.50 vs. 1.55, P < 0.001). Differences between the two groups in favour of the intervention were observed throughout the study period. More participants in the intervention group had good adherence compared with the nonintervention group (36% vs. 14%, P < 0.001). Conclusion: Regular, continued patient support from dermatological nurses increased the efficacy of psoriasis treatment, improved quality of life and enhanced long‐term adherence to topical antipsoriatic drugs. However, there is still room for more improvement. [ABSTRACT FROM AUTHOR]

Background: Tralokinumab is a fully human monoclonal antibody that neutralizes the activity of interleukin‐13, a key pathogenic driver of atopic dermatitis (AD). Clinical trials including adults with moderate‐to‐severe AD, of up to 52 weeks' duration, showed tralokinumab was efficacious and well tolerated. Objectives: To characterize the safety profile of tralokinumab for the treatment of moderate‐to‐severe AD. Methods: Safety and laboratory measures were assessed in pooled analyses of phase II and III placebo‐controlled clinical trials of tralokinumab in moderate‐to‐severe AD (NCT02347176, NCT03562377, NCT03131648, NCT03160885, NCT03363854). Results: In total, 2285 patients were randomized in the initial treatment periods up to 16 weeks (1605 tralokinumab, 680 placebo). The frequencies of any adverse event (AE) were 65·7% for tralokinumab and 67·2% for placebo. The respective rates were 640 and 678 events per 100 patient‐years of exposure (ep100PYE); rate ratio 1·0, 95% confidence interval (CI) 0·9–1·1. Serious AEs occurred in 2·1% of patients with tralokinumab and 2·8% with placebo (7·4 and 11·9 ep100PYE; rate ratio 0·7, 95% CI 0·4–1·2). The most common AEs occurring at a higher frequency and rate with tralokinumab vs. placebo were: viral upper respiratory tract infection (15·7% vs. 12·2%; 65·1 vs. 53·5 ep100PYE); upper respiratory tract infection (5·6% vs. 4·8%; 20·8 vs. 18·5 ep100PYE); conjunctivitis (5·4% vs. 1·9%; 21·0 vs. 6·9 ep100PYE); and injection‐site reaction (3·5% vs. 0·3%; 22·9 vs. 4·0 ep100PYE). Some events in safety areas of interest occurred at a lower frequency and rate with tralokinumab vs. placebo: skin infections requiring systemic treatment (2·6% vs. 5·5%; 9·7 vs. 22·8 ep100PYE), eczema herpeticum (0·3% vs. 1·5%; 1·2 vs. 5·2 ep100PYE), opportunistic infections (3·4% vs. 4·9%; 13·0 vs. 21·3 ep100PYE) and serious infections (0·4% vs. 1·1%; 1·3 vs. 3·7 ep100PYE). AEs did not increase with continued maintenance and open‐label treatment, including rates of common or serious AEs and AEs leading to study drug discontinuation. No clinically meaningful changes in mean laboratory measures were observed with treatment up to 1 year. Conclusions: Across the AD population pool from five clinical trials, tralokinumab was well tolerated, with consistent safety findings during treatment of patients with moderate‐to‐severe AD. The safety profile during prolonged tralokinumab treatment was consistent with that during the initial treatment period; the frequency of events did not increase over time. What is already known about this topic?Tralokinumab is a fully human monoclonal antibody that specifically neutralizes interleukin‐13, a key cytokine driving skin inflammation and epidermal barrier dysfunction in atopic dermatitis (AD).In clinical trials in moderate‐to‐severe AD, tralokinumab provided significant and early improvements in the extent and severity of AD and was well tolerated, with an overall safety profile comparable with placebo over 52 weeks. What does this study add?We report the frequency and rate of adverse events (AEs) from pooled observations of over 2000 patients from five phase II and phase III placebo‐controlled clinical trials of tralokinumab in moderate‐to‐severe AD.During initial treatment up to 16 weeks, the frequencies of any AE and of serious AEs were similar for tralokinumab and placebo. AE rates did not increase with continued treatment up to 52 weeks.Common AEs occurring more frequently with tralokinumab vs. placebo were viral and upper respiratory tract infection, conjunctivitis and injection‐site reaction. Some events occurred at a lower frequency and rate with tralokinumab vs. placebo, such as skin infections requiring systemic treatment, eczema herpeticum and opportunistic and serious infections.No clinically meaningful changes in mean laboratory measures were observed. [ABSTRACT FROM AUTHOR]

Summary: Background: Interleukin‐23 inhibitors are effective and safe for treating moderate‐to‐severe plaque psoriasis. Objectives: To evaluate the efficacy and safety of mirikizumab in adult patients with moderate‐to‐severe plaque psoriasis through 52 weeks in a phase III randomized controlled trial. Methods: OASIS‐1 (NCT03482011) was a double‐blind, placebo‐controlled, randomized withdrawal, phase III trial. Patients (n = 530, randomized 4 : 1) received subcutaneous mirikizumab 250 mg or placebo every 4 weeks (Q4W) through week 16. Coprimary endpoints were superiority of mirikizumab vs. placebo on static Physician's Global Assessment (sPGA; score of 0 or 1 with ≥ 2‐point improvement) and ≥ 90% improvement in Psoriasis Area and Severity Index (PASI 90, responders) at week 16. Mirikizumab responders were rerandomized (1 : 1 : 1) to mirikizumab 250 mg every 8 weeks (Q8W), mirikizumab 125 mg Q8W, or placebo Q8W through week 52. Secondary endpoints were evaluated at weeks 16 and 52. Safety was monitored in all patients. Results: All primary and key secondary endpoints were met. At week 16, sPGA(0,1) responses were significantly greater with mirikizumab (293 of 423, 69·3%) than placebo (seven of 107, 6·5%) (P < 0·001). PASI 90 response was also greater with mirikizumab (272 of 423, 64·3%) than placebo (seven of 107, 6·5%) (P < 0·001). Significantly more patients in the mirikizumab arms achieved PASI 75 and PASI 100 (mirikizumab 349, 82·5% and 137, 32·4%; placebo 10, 9·3% and 1, 0·9%, respectively; all P < 0·001). At week 52, PASI 90, PASI 100 and sPGA(0,1) responses were mirikizumab 250Q4W/placeboQ8W (N = 91; 19%, 10%, 18%), mirikizumab 250Q4W/125Q8W (N = 90; 86%, 59%, 86%) and mirikizumab 250Q4W/250Q8W (N = 91; 86%, 60%, 82%; all P < 0·001), respectively. Rates of serious adverse events were similar across treatments (induction: mirikizumab 1·2% vs. placebo 1·9%; maintenance: mirikizumab 250Q4W/125Q8W 1%, mirikizumab 250Q4W/250Q8W 3% vs. placebo 3%). No deaths occurred. Conclusions: Mirikizumab was superior to placebo at week 16 and maintained efficacy through week 52, with no new safety signals. What is already known about this topic?Interleukin (IL)‐23 is a key cytokine in the pathogenesis of psoriasis. Drugs targeting the p19 subunit of IL‐23 have recently been approved for the treatment of adult patients with moderate‐to‐severe plaque psoriasis.Patients with moderate‐to‐severe plaque psoriasis achieved significantly greater improvements in skin measures and patient‐reported quality‐of‐life measures after 16 weeks when treated every 8 weeks with mirikizumab compared with placebo in a phase II clinical trial. What does this study add?Compared with placebo, mirikizumab demonstrated high levels of efficacy at week 16 in a large phase III trial; safety profiles were similar between the mirikizumab and placebo arms.After week 16, patients maintained on doses of mirikizumab 250 mg every 8 weeks (Q8W) or 125 mg Q8W showed similar efficacy and favourable safety profiles over 52 weeks, whereas patients switched to placebo gradually lost efficacy over time. [ABSTRACT FROM AUTHOR]

Background: Responses to the systemic treatments commonly used to treat psoriasis vary. Biomarkers that accurately predict effectiveness and safety would enable targeted treatment selection, improved patient outcomes and more cost‐effective healthcare. Objectives: To perform a scoping review to identify and catalogue candidate biomarkers of systemic treatment response in psoriasis for the translational research community. Methods: A systematic search of CENTRAL, Embase, LILACS and MEDLINE was performed for relevant articles published between 1990 and December 2021. Eligibility criteria were studies involving patients with psoriasis (any age, n ≥ 50) reporting biomarkers associated with systemic treatment response. The main outcomes were any measure of systemic treatment efficacy or safety. Data were extracted by one reviewer and checked by a second; studies meeting minimal quality criteria (use of methods to control for confounding) were formally assessed for bias. Candidate biomarkers were identified by an expert multistakeholder group using a majority voting consensus exercise and mapped to relevant cellular and molecular pathways. Results: Of 71 included studies (67 studying effectiveness outcomes and eight safety outcomes; four studied both), most reported genomic or proteomic biomarkers associated with response to biologics (48 studies). Methodological or reporting limitations frequently compromised the interpretation of findings, including inadequate control for key covariates, lack of adjustment for multiple testing, and selective outcome reporting. We identified candidate biomarkers of efficacy to tumour necrosis factor inhibitors [variation in CARD14, CDKAL1, IL1B, IL12B and IL17RA loci, and lipopolysaccharide‐induced phosphorylation of nuclear factor (NF)‐κB in type 2 dendritic cells] and ustekinumab (HLA‐C*06:02 and variation in an IL1B locus). None were supported by sufficient evidence for clinical use without further validation studies. Candidate biomarkers were found to be involved in the immune cellular crosstalk implicated in psoriasis pathogenesis, most notably antigen presentation, T helper (Th)17 cell differentiation, positive regulation of NF‐κB, and Th17 cell activation. Conclusions: This comprehensive catalogue provides a key resource for researchers and reveals a diverse range of biomarker types and outcomes in the included studies. The candidate biomarkers identified require further evaluation in methodologically robust studies to establish potential clinical utility. Future studies should aim to address the common methodological limitations highlighted in this review to expedite discovery and validation of biomarkers for clinical use. What is already known about this topic?Responses to the systemic treatments commonly used to treat psoriasis vary.Biomarkers that accurately predict effectiveness and safety would enable targeted treatment selection, improved patient outcomes and more cost‐effective healthcare. What does this study add?This review provides a comprehensive catalogue of investigated biomarkers of systemic treatment response in psoriasis.A diverse range of biomarker types and outcomes was found in the included studies, serving as a key resource for the translational research community. [ABSTRACT FROM AUTHOR]

Summary: Background: Baricitinib, an oral selective Janus kinase (JAK)1 and JAK 2 inhibitor, was shown to improve the signs and symptoms of moderate‐to‐severe atopic dermatitis (AD). Objectives: To evaluate the efficacy and safety of baricitinib with background topical corticosteroids (TCS) in patients with moderate‐to‐severe AD and inadequate response, intolerance or contraindication to ciclosporin A (CA). Methods: In this double‐blind, randomized, placebo‐controlled, phase III study, patients were randomized 1: 1: 2: 1 to placebo (N = 93), baricitinib 1 mg (N = 93), 2 mg (N = 185) or 4 mg (N = 92) with background TCS. The primary endpoint was the proportion of patients receiving baricitinib 4 mg or 2 mg (+ TCS) vs. placebo + TCS who achieved ≥ 75% improvement from baseline in the Eczema Area and Severity Index (EASI 75) at week 16. Results: Baricitinib 4 mg + TCS was superior to placebo + TCS for EASI 75 (4 mg: 32%, placebo: 17%, P = 0·031) at week 16 and for improvements in itch, skin pain and number of night‐time awakenings owing to itch. Improvements were maintained through 52 weeks of treatment. Treatment‐emergent adverse events (TEAEs) were more common with baricitinib than placebo (+ TCS); most were mild or moderate. The most frequent TEAEs with baricitinib 4 mg + TCS were nasopharyngitis, herpes simplex, influenza and headache. No deaths or deep vein thromboses were reported. Conclusions: Baricitinib 4 mg + TCS improved the signs and symptoms of moderate‐to‐severe AD through 52 weeks of treatment in patients with inadequate response, intolerance or contraindication to CA. The safety profile was consistent with previous studies of baricitinib in moderate‐to‐severe AD. What is already known about this topic?Ciclosporin A is indicated for the treatment of atopic dermatitis that is refractory to topical therapies. However, its use is limited by safety concerns and it may not provide adequate response for some patients.Baricitinib, an oral selective Janus kinase (JAK)1 and JAK2 inhibitor, has been shown to improve the signs and symptoms of moderate‐to‐severe atopic dermatitis as a monotherapy or in combination with topical corticosteroids. What does this study add?Baricitinib combined with background low‐ or moderate‐potency topical corticosteroids provided improvements in the signs and symptoms of moderate‐to‐severe atopic dermatitis through 1 year of treatment in patients with a contraindication, intolerance or failure to respond to ciclosporin A.The most common treatment‐emergent adverse events with baricitinib 4 mg were nasopharyngitis, herpes simplex, influenza and headache.The safety profile was consistent with previous studies in patients with moderate‐to‐severe atopic dermatitis. [ABSTRACT FROM AUTHOR]

Background Based on studies implicating the type 2 cytokine interleukin 13 (IL-13) as a potential contributor to critical coronavirus disease 2019 (COVID-19), this trial was designed as an early phase 2 study to assess dupilumab, a monoclonal antibody that blocks IL-13 and interleukin 4 signaling, for treatment of inpatients with COVID-19. Methods We conducted a phase 2a randomized, double-blind, placebo-controlled trial (NCT04920916) to assess the safety and efficacy of dupilumab plus standard of care vs placebo plus standard of care in mitigating respiratory failure and death in those hospitalized with COVID-19. Results Forty eligible subjects were enrolled from June to November of 2021. There was no statistically significant difference in adverse events nor in the primary endpoint of ventilator-free survival at day 28 between study arms. However, for the secondary endpoint of mortality at day 60, there were 2 deaths in the dupilumab group compared with 5 deaths in the placebo group (60-day survival: 89.5% vs 76.2%; adjusted hazard ratio [HR], 0.05 [95% confidence interval {CI},.004–.72]; P  = .03). Among subjects who were not in the intensive care unit (ICU) at randomization, 3 subjects in the dupilumab arm were admitted to the ICU compared to 6 in the placebo arm (17.7% vs 37.5%; adjusted HR, 0.44 [95% CI,.09–2.09]; P  = .30). Last, we found evidence of type 2 signaling blockade in the dupilumab group through analysis of immune biomarkers over time. Conclusions Although the primary outcome of day 28 ventilator-free survival was not reached, adverse events were not observed and survival was higher in the dupilumab group by day 60. Clinical Trials Registration NCT04920916. [ABSTRACT FROM AUTHOR]

Background: Network meta‐analyses (NMAs) have become successful in addressing gaps in the comparative effectiveness of systemic treatments in moderate‐to‐severe psoriasis. However, their increasing number carries both a risk of overlap and reproducibility issues that can hamper clinical decision‐making. Objectives: In this overview, we aimed to assess redundancy across these NMAs and to describe their characteristics. Materials and methods: We considered all systematic reviews with NMAs of randomized controlled trials that included adult patients with moderate‐to‐severe psoriasis and that evaluated the efficacy and/or safety of systemic treatments compared with placebo or with an active comparator. PubMed/MEDLINE, Epistemonikos, PROSPERO and the Evidence update of the Centre of Evidence‐Based Dermatology of the University of Nottingham were searched up to 25 February 2021. Our main outcome was the number per year of redundant NMAs and the extent of their overlap. We also described their features, especially, the confidence in the results of the reviews, the funding of the studies and the presence of spin (a description that overstates efficacy and/or understates harm), reporting issues and methodological characteristics. Results: In total, 47 redundant NMAs were included. Only two of 47 (4%) included all available treatments. Both efficacy and safety were evaluated in 14 of 47 (30%) NMAs and both short‐ and long‐term evaluations were assessed in five of 47 (11%). Confidence in the results was critically low for 39 of 47 (83%) NMAs and only 10 of 47 (21·3%) registered a protocol. Twenty‐six of 47 NMAs (55%) received pharmaceutical funding. Contract research organizations were involved in 19 of 47 (40%) NMAs. Reporting was poor across most of the NMA abstracts and spin was present in all of the abstracts. Almost half of the NMAs failed to consider important limitations such as heterogeneity (considered in 32%) or consistency (considered in 66%). Conclusions: In addition to a duplication of efforts, our overview showed heterogeneous methods and poor confidence in the results in a majority of the included NMAs, further distorted by reporting issues and spin. Clinicians need to interpret NMAs with caution when looking for the most reliable and comprehensive evidence. [ABSTRACT FROM AUTHOR]

Summary: A key challenge in psoriasis therapy is the tendency for lesions to recur in previously affected anatomical locations after treatment discontinuation following lesion resolution. Available evidence supports the concept of a localized immunological 'memory' that persists in resolved skin after complete disappearance of visible inflammation, as well as the role of a specific subpopulation of T cells characterized by the dermotropic CCR4+ phenotype and forming a local memory. Increasing knowledge of the interleukin (IL)‐23/T helper 17 (Th17) cell pathway in psoriasis immunopathology is pointing away from the historical classification of psoriasis as primarily a Th1‐type disease. Research undertaken from the 1990s to the mid‐2000s provided evidence for the existence of a large population of CD8+ and CD4+ tissue‐resident memory T cells in resolved skin, which can initiate and perpetuate immune responses of psoriasis in the absence of T‐cell recruitment from the blood. Dendritic cells (DCs) are antigen‐presenting cells that contribute to psoriasis pathology via the secretion of IL‐23, the upstream regulator of Th17 cells, while plasmacytoid DCs are involved via IL‐36 signalling and type I interferon activation. Overall, the evidence discussed in this review indicates that IL‐23‐driven/IL‐17‐producing T cells play a critical role in psoriasis pathology and recurrence, making these cytokines logical therapeutic targets. The review also explains the clinical efficacy of IL‐17 and IL‐23 receptor blockers in the treatment of psoriasis. [ABSTRACT FROM AUTHOR]

Summary: Pruritus is a hallmark of atopic dermatitis (AD), which affects disease severity and patient quality of life. In AD uncontrolled with first‐line topical therapies or in moderate to severe AD, systemic therapies are used; however, there is a paucity of head‐to‐head trials comparing the effectiveness of these therapies. The aim of this study was to compare the effectiveness of systemic therapies in relieving pruritus in moderate to severe AD in adults, using a meta‐analysis. The PubMed, EMBASE, Medline and CINAHL databases were searched from inception up to 31 May 2020 for randomized, placebo‐controlled trials investigating the effectiveness of systemic therapies on pruritus with moderate to severe AD in patients aged ≥ 16 years. In total, 26 studies (n = 5190 participants) were identified. Compared with placebo, there was a large and statistically significant (P < 0.001 for all) reduction in pruritus [standard mean difference (SMD); 95% CI] with dupilumab every 2 weeks (−0.88; −1.13 to −0.63), dupilumab every 2 weeks plus topical corticosteroids (−0.77; −0.91 to −0.62), dupilumab once weekly (−0.99; −1.29 to −0.68), dupilumab once weekly plus topical corticosteroids (−0.70; −0.81 to −0.59). There was also a large and statistically significant reduction with ciclosporin (−1.30; −2.34 to −0.26; P = 0.01) and a large, although not statistically significant reduction with azathioprine (−0.85; −2.07 to 0.35). There was a small reduction with both mepolizumab (−0.27; −0.89 to 0.35) and interferon‐γ (−0.31; −0.75 to 0.12). Of the investigational drugs, nemolizumab 2.0 mg/kg was the most effective (−8.13; −9.31 to −6.94). The majority of systemic therapies were superior to placebo in reducing pruritus. In particular, the dupilumab studies consistently showed large improvements in pruritus, while nemolizumab showed the strongest antipruritic effects. However, future head‐to‐head trials are required for conclusive evidence. [ABSTRACT FROM AUTHOR]

Summary: Background: Bimekizumab is a monoclonal antibody that selectively inhibits both interleukin (IL)‐17A and IL‐17F, which is currently under investigation for treatment of moderate‐to‐severe plaque psoriasis. Maintenance dosing every 4 weeks is well established with IL‐17 inhibitors for psoriasis. Objectives: To investigate the possible dosing interval during bimekizumab maintenance therapy to maintain clear skin, to inform phase III studies. Methods: Forty‐nine patients with moderate‐to‐severe plaque psoriasis received bimekizumab 320 mg at weeks 0/4, followed at week 16 by bimekizumab 320 mg (n = 17) or placebo (n = 32). Efficacy, safety, pharmacokinetics, immunogenicity and biopsy transcriptomic analyses were assessed to week 28. Results: At week 8, 47% of patients achieved a 100% improvement from baseline in Psoriasis Area and Severity Index (PASI 100), increasing to 57% at week 12 (8 weeks after the second dose) before decreasing. In those who received bimekizumab at week 16, PASI 100 rate increased to comparable peak levels at week 20, but reduced by week 28 to 41% (12 weeks after the third dose). The week 8 transcriptional signature observed in lesional psoriatic skin rapidly normalized to levels consistent with nonlesional skin, resulting in molecular remission. Keratinocyte‐related gene products such as CXCL1 (C‐X‐C motif chemokine ligand 1), IL‐8 (encoded by the CXCL8 gene), CCL20 (C‐C motif chemokine 20), IL‐36γ and IL‐17C were profoundly normalized to levels associated with nonlesional skin. Conclusions: Here, inhibition of IL‐17F in addition to IL‐17A resulted in rapid, deep clinical responses. Additionally, profound normalization of keratinocyte biology and the psoriatic transcriptome was observed, including normalization of both IL17 and IL23 gene expression by week 8. These data provide evidence to support evaluation of bimekizumab maintenance dosing both every 8 and every 4 weeks in phase III clinical trials. [ABSTRACT FROM AUTHOR]

Summary: Background: Dupilumab is an antibody against interleukin‐4 receptor α, used in the treatment of atopic dermatitis (AD). Objectives: To evaluate the efficacy and safety of dupilumab in adult Chinese patients with moderate‐to‐severe AD. Methods: In this randomized, double‐blind, placebo‐controlled, parallel‐group, phase III study, conducted between December 2018 and February 2020, patients with AD received dupilumab (300 mg) or placebo once every 2 weeks for 16 weeks, and were followed up for 12 weeks. The primary efficacy endpoint was the proportion of patients with both an Investigator's Global Assessment score of 0–1 and a reduction from baseline of ≥ 2 points at week 16. Results: Overall, 165 patients (mean age 30·6 years; 71·5% male patients) were randomized; 82 patients were randomized to dupilumab and 83 patients were randomized to placebo. At week 16, 26·8% of patients in the dupilumab group and 4·8% of patients in the placebo group achieved the primary endpoint [difference 22·0%, 95% confidence interval (CI) 11·37–32·65; P < 0·001]. Compared with placebo, higher proportions of patients in the dupilumab group achieved ≥ 75% reduction in the Eczema Area and Severity Index score (57·3% vs. 14·5%; difference 42·9%, 95% CI 29·75–55·97; P < 0·001) and had ≥ 3‐point (52·4% vs. 9·6%; difference 42·8%, 95% CI 30·26–55·34; P < 0·001) and ≥ 4‐point (39·0% vs. 4·8%; difference 34·2%, 95% CI 22·69–45·72; P < 0·001) reductions in weekly average daily peak daily pruritus numerical rating scale scores. The incidence of treatment‐emergent adverse events during the treatment period was similar in the two groups. The incidence of conjunctivitis, allergic conjunctivitis and injection site reaction was higher in the dupilumab group than in the placebo group. Conclusions: In adult Chinese patients, dupilumab was effective in improving the signs and symptoms of AD and demonstrated a favourable safety profile. What is already known about this topic?Two randomized, placebo‐controlled phase III trials (SOLO 1 and SOLO 2) have demonstrated that dupilumab is effective and safe when used in the treatment of atopic dermatitis in adults.However, very few Chinese participants were included and, therefore, the efficacy and safety of dupilumab in this population is unclear. What does this study add?The findings of this randomized, placebo‐controlled phase III trial show that dupilumab is effective in improving the signs and symptoms of atopic dermatitis in adult Chinese patients and has a favourable safety profile in this population. Plain language summary available online [ABSTRACT FROM AUTHOR]

Summary: Background: Accurate assessment of atopic dermatitis (AD) severity is critical when initiating and monitoring therapy. Use of existing research tools such as the Eczema Area and Severity Index (EASI) and Scoring Atopic Dermatitis (SCORAD) is complex and time‐consuming in clinical practice. A previous analysis found the product of validated Investigator's Global Assessment (vIGA) and affected body surface area (BSA) to be an accurate and practical tool for routine assessment of paediatric AD. Objective: To evaluate the IGAxBSA composite as an alternative to EASI or SCORAD for assessment of AD disease severity and disease responsiveness. Methods: The relationship between IGAxBSA, EASI and SCORAD was assessed in a post hoc analysis of pooled data from the dupilumab clinical trial programme in adult and paediatric patients with moderate‐to‐severe AD who had received dupilumab or placebo, with or without topical corticosteroids (TCS). The trials are registered at ClinicalTrials.gov and EudraCT: LIBERTY AD SOLO 1 (NCT02277743, 2014‐001198‐15), LIBERTY AD SOLO 2 (NCT02277769, 2014‐002619‐40), LIBERTY AD SOLO‐CONTINUE (NCT02395133, 2014‐003384‐38), LIBERTY AD CHRONOS (NCT02260986, 2013‐003254‐24), LIBERTY AD CAFÉ (NCT02755649, 2015‐002653‐35), LIBERTY AD ADOL (NCT03054428, 2015‐004458‐16), LIBERTY AD PEDS (NCT03345914, 2016‐004997‐16), LIBERTY AD OLE (NCT01949311, 2013‐001449‐15) and LIBERTY AD PEDS OLE (NCT02612454, 2015‐001396‐40). Results: Using datapoints from pooled dupilumab randomized controlled trials (n = 3473) and open‐label extension trials (n = 3045), we found that IGAxBSA correlated well with EASI and SCORAD, irrespective of treatment group and race (white, Asian, black). IGAxBSA correlated better with objective measures (EASI, SCORAD) than with patient‐ or caregiver‐reported subjective measures. IGAxBSA correlated strongly with EASI and SCORAD in assessing disease change over time (r = 0·90, r = 0·76, respectively; P < 0·0001), and concordance between IGAxBSA‐50/75/90 and EASI‐50/75/90 was excellent (88–94%). Conclusions: IGAxBSA is a valid alternative for assessment of AD disease severity and response over time, compared with EASI or SCORAD in patients with AD, irrespective of race. [ABSTRACT FROM AUTHOR]

Summary: Background: Risankizumab has demonstrated efficacy and safety in patients with moderate‐to‐severe plaque psoriasis in randomized clinical trials. Objectives: To evaluate safety data from risankizumab psoriasis phase I–III clinical trials. Methods: Short‐term safety (through week 16) was analysed using integrated data from five phase II and III clinical trials. Long‐term safety was evaluated using integrated data from 17 phase I–III completed and ongoing trials. Results: Short‐term safety analyses included 1306 patients receiving risankizumab 150 mg and 300 patients receiving placebo [402·2 and 92·0 patient‐years (PY) of exposure, respectively]. Long‐term analyses included 3072 risankizumab‐treated patients (exposure: 7927 PY). The median (excluding four outliers) treatment duration was 2·9 years (range 2 days to 5·9 years). Exposure‐adjusted adverse event rates did not increase with long‐term treatment (318 vs. 171 events per 100 PY for short‐ and long‐term analyses). With long‐term risankizumab treatment, rates of serious adverse events were 7·8 per 100 PY, serious infections 1·2 per 100 PY, nonmelanoma skin cancer (NMSC) 0·7 per 100 PY, malignant tumours excluding NMSC 0·5 per 100 PY, and adjudicated major adverse cardiovascular events 0·3 per 100 PY, with no important identified risks. Limitations include that the study inclusion and exclusion criteria varied and that three studies enrolled ≤ 50 patients. Conclusions: Risankizumab demonstrated a favourable safety profile over short‐ and long‐term treatment in patients with moderate‐to‐severe psoriasis. Whatis already known about this topic? In clinical trials of patients with moderate‐to‐severe plaque psoriasis, risankizumab, a selective interleukin‐23 inhibitor, was well tolerated and efficacious. Whatdoes this study add? In this comprehensive evaluation of risankizumab safety in patients with moderate‐to‐severe psoriasis, adverse event rates were comparable between risankizumab (n = 1306, 402 patient‐years) and placebo (n = 300, 92 patient‐years) in the short‐term (16‐week) analysis set, and were consistent with those in the long‐term analysis (n = 3072, 7927 patient‐years of risankizumab exposure).These findings are consistent with the known safety profile of risankizumab and support its long‐term use in moderate‐to‐severe psoriasis. Linked Comment: S. Mirali et al. Br J Dermatol 2022; 186:394–395. Plain language summary available online [ABSTRACT FROM AUTHOR]

Summary: Background: Tralokinumab, a fully human IgG4 monoclonal antibody that specifically binds with high affinity to interleukin‐13, effectively reduces moderate‐to‐severe atopic dermatitis (AD) when given every 2 weeks. The incidence of conjunctivitis is elevated vs. placebo, but severity and aetiology have not been examined. Objective: To analyse conjunctivitis data recorded in five randomized, placebo‐controlled trials of tralokinumab in adult patients with moderate‐to‐severe AD. Methods: Overall, 2285 adults with AD were studied up to 16 weeks. Cochran–Mantel–Haenszel weights were applied to calculate the adjusted incidence of adverse events. Results: The incidence of conjunctivitis was higher (7·5%) with tralokinumab than with placebo (3·2%). Most events were mild or moderate in severity, and 78·6% and 73·9% of events resolved during the trial in the tralokinumab and placebo groups, respectively. Two (1·4%) events led to the permanent discontinuation of tralokinumab. An increased incidence of conjunctivitis, regardless of treatment group, was associated with more severe baseline AD, and history of allergic conjunctivitis/atopic keratoconjunctivitis, as well as the number of atopic comorbidities. Limitations: This analysis reports events up to week 16 only, with limited confirmation of conjunctivitis and its aetiology by an ophthalmologist, and insufficient reporting of ophthalmic treatments. Conclusions: Treatment with tralokinumab was associated with an increased incidence of conjunctivitis vs. placebo, but these cases were mostly mild and transient. Whatis already known about this topic? Ocular disorders, including conjunctivitis, occur more frequently in patients with atopic dermatitis (AD).When using the interleukin (IL)‐4 and IL‐13 receptor blocking biologic dupilumab, patients with AD in clinical trials and real‐world practice experience higher rates of conjunctivitis, which increases with baseline AD severity.Tralokinumab, a fully human monoclonal antibody, binds specifically to IL‐13 with high affinity.Various rates of conjunctivitis have been observed in different clinical trials of tralokinumab. Whatdoes this study add? This is the first investigation of conjunctivitis in phase III studies of a biological drug specifically targeting IL‐13, in contrast to dupilumab, which targets the IL‐4 and IL‐13 receptorsThe incidence of conjunctivitis was higher with tralokinumab (7·5%) vs. placebo (3·2%); most cases were mild and resolved, or were resolving during study treatment.Risk factors included high AD severity, history of conjunctivitis, disease biomarker levels, and number and type of atopic comorbiditiesThis is the first study to show that some atopic comorbidities have a greater influence on the risk of conjunctivitis than others. Linked Comment: R. Nguyen. Br J Dermatol 2022; 186:391–392. [ABSTRACT FROM AUTHOR]

Objectives Studies have suggested phosphodiesterase 4 (PDE4) inhibition may be associated with weight loss and other cardiometabolic benefits. We evaluated the effect of the PDE4 inhibitor apremilast on body weight and composition, glucose homeostasis, lipid profiles and vascular function in psoriatic disease and whether weight change correlated with therapeutic response. Methods We conducted a prospective, open-label study (Immune Metabolic Associations in Psoriatic Arthritis) of adults receiving apremilast 30 mg as part of routine care for PsA and/or psoriasis. Cardiometabolic, anthropometric and disease activity assessments were performed at baseline (pre-apremilast) and at months 1, 3 and 6 of apremilast treatment in 60 patients. A subgroup underwent further assessment of endothelial function, body composition and adipocyte morphology. Results In patients (median age 54.5 years, 63% women, median BMI 33.2 kg/m2), apremilast was associated with a mean weight loss of 2.2 kg (95% CI 1.4, 3.0; P  < 0.001) and a mean BMI decrease of 0.8 kg/m2 (95% CI 0.5, 1.2; P  < 0.001) after 6 months of treatment. Body composition analysis demonstrated a reduction in total abdominal fat [mean decrease 0.52 L (95% CI 0.08, 0.96), P  = 0.022], principally subcutaneous adipose tissue [mean decrease 0.37 L (95% CI 0.05, 0.68), P  = 0.022]. There was no change in adipocyte diameter, haemoglobin A1c, lipid, glucagon-like peptide-1 or vascular function. Psoriatic disease activity improved with apremilast, although this was not correlated with weight change. Conclusion Following apremilast treatment, we observed weight loss, principally abdominal subcutaneous fat, and improvement in psoriatic disease activity. The latter was independent of weight change, suggesting apremilast likely acts through direct immunological mechanisms. [ABSTRACT FROM AUTHOR]

Summary: Background: Better understanding of the experience of people living with hidradenitis suppurativa (HS) is essential to identify gaps in current patient care and inform healthcare decision‐making. Aim: To describe the patient experience of individuals with HS, including their path to diagnosis, symptom control, treatments, healthcare utilization, patient needs and impact on quality of life. Methods: The Hidradenitis Suppurativa Patient Experience survey was created, extensively reviewed and disseminated through engaging HS‐related patient organizations, physician groups and social media groups. Results: In total, 537 respondents completed the survey; the mean age was 38 years (range 14–73 years) and 95% (510 of 537) were female. The mean number of treatment types per respondent was 15, and included antibacterial soaps (93.3%; 431 of 462), avoidance of tight clothing (90.9%; 419 of 462), use of oral antibiotics (79.7%; 368 of 462), nonprescription drugs (79.7%; 368 of 462) and topical antibiotics (77.1%; 356 of 262). Pain was poorly controlled in 46% of respondents (184 of 401). HS had a negative impact on the ability to work and attend school for 81% of respondents (337 of 415), with 59% (245 of 415) missing at least 2 days of work a month and 16% (66 of 415) missing > 11 days of work. The mean number of misdiagnoses per respondent was three and the median time to diagnosis was 10 years. Conclusion: Individuals with HS experience a delay in diagnosis and have suboptimal control of the disease. We propose 11 recommendations to improve diagnosis, treatment and quality of life for individuals living with HS. [ABSTRACT FROM AUTHOR]