Biologics/Psoriasis

Background: Hidradenitis Suppurativa (HS) is associated with polarisation of the Th17 axis, with significant dysregulation of IL23 and IL17A/C/F cytokines. Recent phase 2 trials of IL23 antagonism in HS have demonstrated a disparate clinical response between genders, with male cohorts demonstrating a higher rate of clinical response compared to females. IL23 is known to interact with androgen receptor signalling pathways and modulates inflammation through macrophages. Therefore, sex hormones may influence Th17 mediated inflammation in HS. Aim: To assess whether clinical response to IL23 antagonism is associated with clinical, hormonal or molecular markers in patients with Hidradenitis Suppurativa. Methods: 26 participants with HS Hurley Stage 2/3 had baseline sex hormones measured and lesional biopsies. IL23 antagonist Risankizumab 150 mg was administered at weeks 0, 4 and 12, with clinical response assessed at week 16 by the HS clinical response (HiSCR). Hormonal and molecular differences between responders and nonresponders (NR) were assessed. Results: 69.2% of participants achieved a HiSCR50 at week 16. Clinical response to IL23 antagonism was associated with male gender, elevated total serum testosterone, and decreased FSH levels. MAPK10 and PLPP4 were identified as differentially expressed genes when clinical responders and NR were stratified. Immunohistochemistry identified elevation of CD11c, IL17A and IL17F positive cells in responders when compared to NR. Furthermore, CD11c was strongly correlated with serum levels of total testosterone and inversely correlated with serum FSH. Conclusion: Serum sex hormones, Th17 inflammation in lesional tissue and the presence of CD11c+cells were associated with clinical response to IL23 antagonism. These findings suggest the potential for targeted therapy in HS.


Bimekizumab efficacy and safety through 3 years in patients with moderate to severe plaque psoriasis: Long-term results from the BE SURE trial and BE BRIGHT open-label extension
Aims: To report bimekizumab (BKZ) 3-year (yr) efficacy and safety in patients from BE SURE (NCT03412747) who entered the associated BE BRIGHT open-label extension (OLE; NCT03598790). Methods: BE SURE: patients randomised to BKZ 320 mg every 4 weeks (wk; Q4W) to Wk56, BKZ Q4W Wk0-16 then Q8W to Wk56, or adalimumab (ADA) 40 mg Q2W Wk0-24 then BKZ Q4W to Wk56 (ADA/BKZ). On completing BE SURE, patients could enrol in BE BRIGHT OLE. At Wk56: dose adjustments (to BKZ Q4W or Q8W) based on achievement of ≥90% improvement from baseline in Psoriasis Area and Severity Index (PASI90); Wk104/next visit: all received BKZ Q8W. Proportions of patients achieving PASI90 and absolute PASI ≤ 2/=0 reported by initial randomization groups (modified non-responder imputation Aims: We evaluated early treatment efficacy and healthrelated quality of life (HRQoL) benefits in patients with moderate to severe plaque psoriasis treated with bimekizumab (BKZ). We also examined the effect of early treatment response on the cumulative impact of psoriasis on HRQoL, as measured by Dermatology Life Quality Index (DLQI), using area under the curve analyses. Methods: Data were pooled for patients randomised to BKZ 320 mg every 4 weeks (wks; Q4W) in BE SURE, BE READY, and BE RADIANT. Through Wk16-48, data were combined for both BKZ maintenance doses (BKZ 320 mg Q4W or Q8W). Proportions of patients achieving DLQI 0/1 (no effect of skin disease on patient's life) were reported at Wk4 by ≥90% reduction in baseline Psoriasis Area and Severity Index (PASI90) and absolute PASI ≤ 2 status; cumulative HRQoL benefits through 48wks were estimated using total area under the curve (AUC 0-48 ) for patients achieving DLQI 0/1 by Wk4 PASI90 and PASI ≤ 2 status. Missing data were imputed as non-response. double-blinded phase 3b trial and OLE). Upon OLE entry, patients were assigned to BKZ treatment based on ≥90% reduction from baseline Psoriasis Area and Severity Index (PASI90) response. We report absolute PASI = 0 (i.e., PASI100 attainment) and absolute PASI ≤ 2 maintenance through 2 years (Wk48 of OLE) among Wk16 responders who received continuous BKZ maintenance dosing from Wk16 (320 mg every 4wks [Q4W]/Q4W/Q4W or Q4W/Q8W/Q8W) and entered the OLEs. Missing efficacy data were imputed using modified non-responder imputation (mNRI); patients discontinuing treatment due to lack of efficacy were considered non-responders; other missing data were imputed using multiple imputation. Wk16 responder rates (NRI) are included for context. Treatment-emergent adverse events (TEAEs) are reported as exposure-adjusted incidence rates (EAIRs) per 100 patient-years through 2 years for patients who received ≥1 BKZ dose. Aims: Despite many systemic treatments being approved and reimbursed for treatment of patients with moderate to severe psoriasis (PsO) in Australia, many patients remain undertreated. There is limited evidence available on how patients and physicians make trade-offs for oral and injectable medications in the Asia-Pacific region. This study aimed to identify treatment features that patients and physicians value, evaluate the relative importance of different treatment features, and understand how patients and physicians trade off in their decision making for oral vs. injectable medications. Methods: In phase 1, a targeted literature review, 15 qualitative interviews, and clinician input were used to develop a survey including a Discrete Choice Experiment (DCE) to explore trade-offs. In phase 2, Australian dermatologists and patients completed a 25-minute online survey. The DCE allowed a choice between two hypothetical treatment alternatives: 'oral' or 'subcutaneous injection.' Nine DCE treatment features were displayed in each choice set: injection device, PsO reduction, time to initial and to maximum improvement, risk of minor and of severe side effects, frequency of administration, monitoring requirement, and storage condition. Results: Phase 2 included 178 patients and 43 dermatologists. The DCE showed that PsO reduction and mode of administration drove the majority of decision-making. Fear of needles also significantly impacted treatment mode choice, and 35% of patients reported having needle fear of 5 or greater on a scale of 0 (do not mind them) to 10 (avoid at all costs) (median = 3). Among respondents, 59.7% of patients (with a median needle fear) and 72.8% of physicians preferred oral vs. injectable medications with once-weekly dosing for moderate disease, holding all treatment features equal. For severe disease, 50.1% of patients and 55.6% physicians preferred oral treatment, holding all treatment features equal. Conclusion: These findings highlight the unmet need driven by patients' and physicians' preference for efficacious oral treatments.

OPEN Health Evidence & Access
Aims: This post hoc analysis of patients with moderate to severe plaque psoriasis in the 52-week POETYK PSO-1 trial (NCT03624127) assessed the cumulative clinical benefit in two distinct treatment pathways: those who initiated deucravacitinib vs. those who initiated apremilast and either continued through 52 weeks or switched to deucravacitinib at Week 24 following lack of response. Methods: Patient-level data from the POETYK PSO-1 trial were used to assess the cumulative clinical benefit for deucravacitinib and apremilast initiators from randomization to Week 52. The cumulative benefit was calculated using the total area under the curve (AUC) of the proportion of responders for PASI 75 and sPGA 0/1, measured in % response times weeks [% x weeks]. The result was standardised as a percentage of the maximum possible benefit of 5200 [% x weeks] (ie, 52 weeks of 100% response in each week). A regression model was used to adjust for baseline characteristics. Nonresponder imputation was used for missing responses, per protocol definition. Results: Among apremilast initiators (n = 168), 87 patients continued apremilast and 54 crossed over to deucravacitinib after Week 24 due to lack of response (<PASI 50). At Week 52, deucravacitinib initiators (n = 332) experienced greater cumulative benefit than apremilast initiators for PASI 75 (2979 vs. 1988  Dupilumab is the only IL-4Rα/IL-13 receptor inhibitor that has been approved for treatment of moderate to severe atopic dermatitis in Australia. While dupilumab has demonstrated significant clinical reductions in the severity of atopic dermatitis for many patients, phenotypic switching from atopic dermatitis to psoriasiform reactions has been highlighted as one of the uncommon but notso-insignificant reactions associated with Dupilumab. The postulated theories to date relate to dupilumab's Th-2 blockade which results in a shift towards the Th-1 axis, where known elevated pro-inflammatory cytokines belong to the Th-1 pathway have been demonstrated to drive psoriasis mediated inflammation. Here we report a case series of 4 patients who were treated with dupilumab for atopic dermatitis, all of whom subsequently experienced a phenotypic switch to psoriasis. While each of the 4 patients had an initial clearance of eczema with dupilumab, shortly afterwards they all presented with a new flare of psoriasis: one patient developed generalised pustular psoriasis 2-weeks post-loading dose of dupilumab, another patient presented with classic psoriasiform plaques with some admixed pustules, and the other two patients developed classic plaque psoriasis. Dupilumab was ceased for all 4 patients as there appeared to be an uncommon causal association explaining their phenotypic switch, their diseases were subsequently managed with varying psoriatic-targeted treatments. Herein, we describe the clinic-pathologic features of these patients who developed psoriasis while being treated with dupilumab, and we discuss the different managements of their psoriasiform reactions. Further research is required to understand the cause of this phenomenon, whether certain attributes predispose a patient to the phenotypic switch and whether management of the subsequent psoriasiform reaction requires care in addition to regular psoriatic management. Subcorneal pustular dermatosis, also called Sneddon-Wilkinson disease, is a rare neutrophilic skin condition involving symmetrical eruptions of sterile subcorneal pustules. Subcorneal pustular dermatosis has been associated with various rheumatological and haematological conditions and and may be drug-induced including due to some immunomodulatory medications. We present the case of a 77-year-old male with severe eczema and asthma unresponsive to benralizumab, an IL-5 inhibitor, who was subsequently treated with dupilumab. The patient's eczema responded well to dupilumab 300 mg fortnightly. However, 3 months following dupilumab initiation, the patient developed a new distinct rash -a widespread well-demarcated erythematous annular eruption with peripheral pustules and scale over flexural areas (posterior knee, axillae, buttock, groin, medial thigh and back). The temporal appearance of the new eruption followed a cyclical pattern, peaking within 48 hours of dupilumab use and subsiding gradually until the next fortnight. The patient was systemically well, albeit with a mildly raised WCC (14.8 × 10 6 ) and neutrophil (13.4 × 10 6 ) counts. Histopathology taken from the abdomen and thigh demonstrated a spongiotic reaction with hyperkeratosis and intracorneal pustule formation, with negative PAS staining and negative direct immunofluorescence. A clinicopathological diagnosis of subcorneal pustular dermatosis secondary to dupilumab was made. The first line agent dapsone was trialled up to 75 mg daily and dupilumab was ceased. Within 2 months of dapsone use and ceasing dupilumab, the patient's subcorneal pustular dermatosis had mostly resolved. While other immunomodulatory agents such as adalimumab and gefitinib have been previously implicated with precipitating this disease, this is the first reported case to our knowledge of subcorneal pustular dermatosis following dupilumab use.

A case of alopecia areata totalis following dupilumab for severe atopic dermatitis
Jessica Zhuang 1 ; Leith Banney 1 ; Emily Shao 2 1 Queensland Health; 2 University of Queensland, Brisbane, Queensland, Australia Introduction: Dupilumab is a monoclonal antibody which inhibits IL-4 and IL-13 and is increasingly being prescribed for severe atopic dermatitis. Adverse events include injection site reactions, conjunctivitis, and increased risk of herpes-simplex infections. Dupilumab has been prescribed off-label for conditions including chronic spontaneous urticaria, prurigo nodularis, and alopecia areata. We describe a case of dupilumab inducing alopecia areata totalis. Case study: A 63-year-old female was prescribed 300 mg subcutaneous dupilumab fortnightly for severe atopic dermatitis. Other than a history of left sided breast cancer treated 14 years ago, she had no significant medical conditions and was prescribed no other medications. She noted rapid and patchy hair loss over the scalp after 4 months of dupilumab treatment. During this time, no other medications were commenced. She was seen by a dermatologist and alopecia totalis, likely secondary to dupilumab, was diagnosed clinically. Discussion: The pathophysiology of atopic dermatitis involves excessive T-helper (Th)2 and Th22 activity, as well as increased inflammation mediated by interleukin (IL)-4, IL-5, IL-13 and IL-31. IL-22 which is required for tightjunction formation is also implicated. Dupilumab works by inhibiting IL-4a and IL-13 receptors which are key components of Th2-mediated inflammation in atopic dermatitis. Similarly, the pathophysiology of alopecia areata is complex and involves Th2 pathways, IL-9, phosphodiesterase (PDE)4, Th17/IL-23. Dupilumab has been reported to both be a precursor to development of and remission of alopecia areata. While in some cases Th2 inhibition appears to improve alopecia areata, Th2 inhibition induced by dupilumab may amplify Th17/IL-23 pathways that could stimulate or induce alopecia areata in other patients. Conclusion: This is the seventeenth case of alopecia areata and to our knowledge the first case of alopecia areata totalis secondary to dupilumab. This case highlights further need for research in this area to assess the relationship between dupilumab and alopecia areata. Introduction: Dupilumab is a monoclonal antibody which inhibits IL-4 and IL-13 and is increasingly being prescribed for Indirect comparison of the short-, mid-, and longterm efficacy of treatments for moderate to severe plaque psoriasis: A systematic review and network meta-analysis

IVDP), University Medical Center Hamburg-Eppendorf (UKE), Hamburg, Germany
Aims: Deucravacitinib demonstrated superior efficacy versus apremilast and placebo in two phase 3 randomised controlled trials (RCTs) in patients with moderate to severe plaque psoriasis. A systematic review (SLR) and network meta-analysis (NMA) were performed, indirectly comparing deucravacitinib with other relevant systemic biologic/nonbiologic treatments. Methods: Electronic databases were searched through October 2021 for RCTs of systemic treatments in adults with moderate to severe psoriasis, reporting Psoriasis Area and Severity Index 75% (PASI 75) response rates. NMA was performed using multinomial random effects models adjusting for baseline-placebo risk to estimate PASI 75 responses over short-, mid-, and long-term follow-ups (Weeks 10-16, 24-28, and 44-60, respectively). Phase 3 trial data were only included when nonresponder imputation was applied. Conclusions: Among oral treatments, deucravacitinib provided the best efficacy across time points. At 52 weeks, the PASI 75 response rate for deucravacitinib was similar to first-generation biologics. Once approved, deucravacitinib will be a potentially valuable new treatment for patients with moderate to severe psoriasis.

TikTok and #Psoriasis: A cross-sectional study of content quality
Marra Aghajani 1 ; Rhian Aghajani 2 1 Royal North Shore Hospital, Pyrmont, New South Wales, Australia; 2 Royal North Shore Hospital, Sydney, New South Wales, Australia Aims: Social media platforms are increasingly being utilised to disseminate dermatology related information. Currently the fifth most-used social media platform worldwide, TikTok has nearly two billion monthly active users. Our objective was to describe and assess the quality of psoriasis-related content on TikTok. Methods: We queried the TikTok application for videos tagged with "#psoriasis" in January 2023. Of the top 225 videos, 209 met the inclusion criteria and were classified by content, impact (including view, likes, comments and shares) and quality via the Global Quality Scale (GQS) and modified DISCERN instrument. Results: At the time of analysis, "#psoriasis" had a total of 1.7 billion views. Majority of top uploads were by laypeople (n = 194, 89%), who received a significantly higher number of views compared to videos uploaded by physicians (p = 0.027). The mean score of all uploads using the GQS and DISCERN instrument was 1.73 (SD 0.92) and 1.07 (SD 0.96), respectively, indicating serious shortcomings in video quality. The quality of video content provided by physicians was significantly higher when compared to uploads by laypeople (p < 0.001). Videos of poorest quality as per the GQS description had a significantly higher mean number of views (p = 0.004), likes (p = 0.010) and shares (p = 0.015) when compared to remaining uploads. Treatment with home remedies/diet modification (41.6%) and anecdotes (34.4%) were the most popular video categories; these videos were more likely to be uploaded by laypeople (p < 0.001) and were associated with the lowest GCS and DISCERN scores (p < 0.001). Conclusions: Overall, psoriasis-related information on TikTok was of poor quality, with the vast majority of videos produced by laypeople. A greater presence of dermatologists on TikTok may assist in limiting the distribution of misleading content and promote evidence-based information.

Refractory classic pityriasis rubra pilaris treated with tildrakizumab
Kevin Phan 1 ; Alvand Amiri 2 1 NSW Health, New South Wales, Australia; 2 Lotus Dermatology, Newcastle, New South Wales, Australia Pityriasis rubra pilaris (PRP) is a rare cutaneous disorder characterised by reddish-orange scaling patches with classically island of sparing and waxy palmoplantar keratoderma. We report the case of a 45-year old man who presented with an erythematous and scaly eruption who had classic features of PRP including palmoplantar keratoderma and nail dystrophy. He was initially treated with topical emollients, corticosteroids and acitretin 0.5 mg/kg/ day. At 1-month follow-up, the eruption had progressed to become generalised and erythrodermic and required hospitalisation. Methotrexate was not chosen due to its slower onset of action and patient preference for fewer needles precluded TNF-alpha inhibitors. Based on some recent case report evidence suggesting efficacy of IL-23 p19 subunit inhibitors, treatment with tildrakizumab was initiated at week 0, week 4, and 12-weekly as per psoriasis protocol. Over the next 4-weeks, there was significant improvement in body surface involved by PRP. This case further adds to the promising evidence supporting IL-23 inhibitors as a treatment option for PRP. PRP is resistance to standard treatment options. Tildrakizumab represents another option with reassuring longer-term data in terms of his safety profile. Aims: Biologics have significantly improved clinical outcomes in terms of quality of life and objective skin clearance compared to traditional systemic therapies. Despite this, data pertaining to the local experience and outcomes has been lacking. Drug survival, which refers to the time to treatment discontinuation, provides a surrogate measure of the effectiveness of a biologic in a real-world setting. The aim of this study was to review drug survival of biologics in psoriasis across two Australian hospitals. Methods: Retrospective data from outpatient Dermatology biologic clinics in Westmead Hospital and Royal Prince Alfred Hospital (Sydney, Australia) from April 2006 to December 2020 were collated. This data included baseline characteristics, treatment courses received and survival data. Biologics included were adalimumab (n = 97), etanercept (n = 26), infliximab (n = 70), tildrakizumab (n = 11), risankizumab (n = 36), guselkumab (n = 35), ustekinumab (n = 143), secukinumab (n = 100) and ixekizumab (n = 59). Drug survival data was analysed using Kaplan-Meier survival analysis. Results: In total, 312 patients underwent 577 treatment courses. Guselkumab (n = 35) had the longest 3-year drug survival rate of 94.2 ± 4.0%. This was followed by ixekizumab (66.0% ± 7.9, n = 59). In further analysis of biologic-naïve patients (n = 295), guselkumab (n = 12) had the highest 1-and 3-year drug survival rate of 100%. This was followed by ixekizumab (n = 23) which had 1-and 3-year survivals of 95.5% ± 4.4 and 72.0% ± 13.3 respectively. Among biologic-experienced patients (n = 282), guselkumab (n = 23) had the highest 1-year survival (91.1% ± 6.0), and ixekizumab (n = 36) had the highest 3year survival (62.0% ± 9.3). Conclusions: To our knowledge, this is the first Australian study that has reported on drug survival that includes outcomes from newer biologics. Overall, this data provides insight into patterns of care from a local experience that may help guide the management of moderate-to-severe psoriasis.

Drug survival of biologics in psoriasis in an Australian population: A retrospective 15-year study of patients' experiences
Aim: Hidradenitis suppurativa (HS) is a difficult-tomanage, chronic inflammatory skin disease, with limited effective treatment options. Here, the primary endpoint (week 16) results from SUNSHINE (NCT03713619) and SUNRISE (NCT03713632), 2 double-blind, identical, phase 3 randomised controlled trials of secukinumab in patients with moderate to severe HS, are reported. Methods: In both trials, adult patients with moderate to severe HS were randomised to receive subcutaneous secukinumab 300 mg every 2 (SECQ2W) or 4 weeks (SECQ4W), or placebo. The primary objective of both trials was to demonstrate the superiority of secukinumab over placebo with respect to the proportion of patients achieving a hidradenitis suppurativa clinical response at week 16. Key secondary endpoints included the proportion of patients experiencing flares over 16 weeks, percentage change from baseline in abscess and inflammatory nodule count and the proportion of patients with NRS30 (skin pain) response (reported as pooled data of both trials) at week 16. placebo [31.2%]) and met all secondary endpoints, except for the proportion of patients experiencing flares (met only in SUNSHINE). SECQ4W also demonstrated clinical efficacy compared to placebo; however, the primary (46.1% vs. 31.2%) and secondary endpoints were only met in SUNRISE (excluding pain, reported as pooled data). Secukinumab was well-tolerated with no new or unexpected safety signals, consistent with its well-established safety profile. Conclusion: In SUNSHINE and SUNRISE, secukinumab was clinically effective in improving signs and symptoms at week 16 in patients with moderate to severe HS, with a favourable safety profile. Acrodermatitis continua of Hallopeau (ACH) is a rare, chronic form of pustular psoriasis, primarily affecting the fingers, toes and nails. It is characterised by recurrent pustules, with erythema and induration. ACH is often refractory to systemic therapies for pustular psoriasis and as such, treatment is often guided by case reports. In this case report, we describe the use of tildrakizumab, a humanised monoclonal antibody targeting interleukin-23, in a patient with severe ACH. The patient had a history of generalised pustular psoriasis affecting her abdomen and limbs that had progressed to acrodermatitis of Hallopeau. Multiple topical therapies and acitretin had been failed, and the patient had contraindications to methotrexate and cyclosporin. An excellent response was seen after 3 months' treatment with tildrakizumab, which continued to improve at 6 and 12 month reviews. This case adds to the limited literature on acrodermatitis continua of Hallopeau, and suggests that tildrakizumab may be a viable treatment option for patients with severe ACH who have failed traditional systemic therapies or other biologic agents. Further research is needed to confirm the safety and efficacy of tildrakizumab in this patient population. We also provide a review of the current literature on acrodermatitis continua of Hallopeau and treatment strategies for this debilitating condition. Introduction: PSoHO is a 3-year, international, prospective, non-interventional cohort study comparing the effectiveness of anti-IL-17A biologics to other approved biologics for moderate-to-severe psoriasis (PsO). This interim analysis describes outcomes through Month (M)12. Methods: This analysis included 910 patients with nonmissing data for PASI90 or sPGA(0/1) at M12. The anti-IL17A biologic cohort was compared with other biologic therapies at W12, M6 and M12, and for each individual treatment. Longitudinal analysis used generalised linear mixed models (GLMM) based on non-responder imputation. Results: In this analysis, 43.1% (n = 392) of patients received ixekizumab (n = 272) or secukinumab (n = 120) in the anti-IL-17A cohort and 56.9% (n = 518) other biologics. At baseline, the mean sPGA score was 3.2(0.8) and PASI scores were 14.9(8.4) and 14.7(8.6), for anti-IL-17A and other biologics cohorts, respectively. Differences (p < 0.05) between cohorts included mean age (47.0 versus 44.7 years), prior conventional therapy (74.7% versus 83.0%) and psoriatic arthritis (24.5% versus 17.6%). The response rate in the anti-IL-17A cohort was statistically (p < 0.05) higher for PASI90 and/or sPGA(0/1) at W12 and M6 with no significant difference at M12, and significantly higher for PASI100 at all timepoints. At M12, a higher proportion (p < 0.001) of patients in the anti-IL-17A cohort (64.3%) compared to the other biologics cohort (48.6%) had maintained durability of response. Conclusions: In this interim analysis, durability of treatment effectiveness was high in patients with moderateto-severe PsO receiving biologic therapies in a real-world setting. The highest rate for this outcome was observed for patients treated with anti-IL-17A biologics at M12.  Dermatology,Queen's University,and Probity Medical Research,Peterborough,Ontario,Canada;3 Icahn School of Medicine at Mount Sinai,New York,New York,USA;4 Nihon University School of Medicine,Tokyo,Japan;5 Eli Lilly and Company,Indianapolis,Indiana,USA;6 Oregon Medical Research Center,Portland,Oregon,USA;7 Eli Lilly and Company,West Ryde,New South Wales,Australia Objective: To summarise the safety outcomes from over 18,000 patient-years (PY) of exposure (over 5 years) to ixekizumab in adult patients with moderate-to-severe psoriasis. Methods: Long-term safety of ixekizumab was assessed from 15 randomised clinical trials. Treatment-emergent adverse events (TEAEs) and adjusted incidence rates (IRs) per 100 PY within 1-year time periods through 19 March 2021 were calculated for all patients treated with ≥1 dose of ixekizumab. Major adverse cerebro-cardiovascular events (MACE) and inflammatory bowel disease (IBD) reported cases were adjudicated. Results: A total of 6892 adult patients with a cumulative exposure of 18,025.7 PY were included. The IRs per 100 PY for any TEAE and SAEs were 32.5 and 5.4, respectively. IR for discontinuation due to AE was 2.9. The predominant cause of death was MACE (n = 17). IR of serious infections was low (1.3). There were no confirmed cases of reactivation of tuberculosis. IR of Candida infections (IR = 1.9) was low; no systemic cases were reported. IRs of injection site reactions and allergic/hypersensitivity reactions (most frequent: dermatitis, eczema, urticaria) were 5.9 and 5.6, respectively; no case of anaphylaxis occurred. IRs were low for malignancies, depression, cytopenia, and MACE (all ≤ 1.2). A total of 31 patients (IR = 0.2) had confirmed IBD (ulcerative colitis, n = 18; Crohn disease, n = 13). Across safety topics, IRs decreased or remained constant over time.

Initial report on the Month 12 results from the Psoriasis Study of Health Outcomes (PSoHO) for patients with moderate-to-severe psoriasis treated with biologics in the real-world setting
Conclusions: Safety profile of ixekizumab remained favourable through 5 years with no increase in yearly IRs from the first year of exposure. No new or unexpected safety events occurred.

COVID-19-related adverse events in the phase 3 POETYK trials of the allosteric tyrosine kinase 2 inhibitor, deucravacitinib, in patients with moderate to severe plaque psoriasis
Stephen Shumack 1 ; Diamant Thaçi 2 ; Kenneth B. Gordon 3 ; Melinda Gooderham 4 ; Andrew Alexis 5 ; Varsha Lalchandani 6 ; Julie Scotto 6 ; Lauren Hippeli 6 ; Matthew J. Colombo 6 ; Subhashis Banerjee 6 ; Tamara Lezhava 6 ; Mark Lebwohl 7 Conclusions: Based on this analysis, deucravacitinib did not appear to increase the risk of COVID-19 nor its progression to severe outcomes. Aims: Deucravacitinib, an oral, selective, allosteric tyrosine kinase 2 inhibitor, is approved in the US, Australia, and other countries for the treatment of adults with moderateto-severe plaque psoriasis who are candidates for systemic therapy or phototherapy. The efficacy and safety of deucravacitinib were assessed in the phase 3 POETYK PSO-1 and PSO-2 trials and the open-label long-term extension (LTE) trial. Methods: The 52-week PSO-1 and PSO-2 trials randomised patients with moderate to severe plaque psoriasis 1:2:1 to placebo, deucravacitinib 6 mg once daily, or apremilast 30 mg twice daily. Patients could then enrol in the LTE trial and receive open-label deucravacitinib 6 mg once daily. Results: 1221 patients were enrolled in the LTE and received ≥1 dose of deucravacitinib. Cumulative exposures in person-years from randomization in PSO-1 or PSO-2 and the LTE were 2166.9 and 2482.0 for efficacy and safety analyses, respectively. At enrollment in the LTE, response rates PASI 75 and static sPGA score of 0 (clear) or 1 (almost clear) were 65.1% and 50.9%, respectively, and were maintained for up to 2 years after initial randomization (Week 48 of LTE: PASI 75, 75.7%; sPGA 0/1, 56.4% [as observed]). Exposure-adjusted incidence rates per 100 person-years for adverse events were similar in the controlled period (Weeks 0-52) of PSO-1 and PSO-2 and during the cumulative PSO-1, PSO-2, and LTE trial period ( Methods: In PSO-3, patients from mainland China, Taiwan, and South Korea were blindly randomised 1:2 to placebo (n = 74) or deucravacitinib 6 mg once daily (n = 146). At Week 16, placebo patients crossed over to deucravacitinib. In PSO-4, Japanese patients with PP (n = 63), generalised pustular psoriasis (GPP, n = 3), or erythrodermic psoriasis (EP, n = 8) received open-label deucravacitinib 6 mg once daily. Endpoints included PASI 75, sPGA 0/1 with a ≥2point improvement from baseline, and ss-PGA 0/1 in patients with a baseline ss-PGA ≥3, at Weeks 16 and 52. Safety was evaluated throughout. Results: In PSO-3, Week 16 PASI 75 and sPGA 0/1 rates were significantly higher with deucravacitinib versus placebo (68.8% vs. 8.1%; 55.6% vs. 6.8%, respectively; p < 0.0001). In PSO-4, Week 16 PASI 75 and sPGA 0/1 rates with deucravacitinib were 76.2% and 82.5% for PP, 66.7% and 0% for GPP, and 37.5% and 50.0% for EP. Week 16 ss-PGA 0/1 rates with deucravacitinib in PP were 62.9% in PSO-3 and 91.2% in PSO-4. In both trials, responses were maintained well through Week 52. The deucravacitinib safety profile in these trials was comparable with that in the two global phase 3 trials, with no new safety findings. Conclusions: Deucravacitinib was effective and well tolerated in Asian patients with moderate to severe psoriasis. Chronic plaque psoriasis is a common, complex inflammatory skin condition affecting up to 2-3% of the Australian population (1,2). It is known to have a significant impact on those who suffer from it, and is associated with anxiety and depression, feelings of social stigmatisation and rejection, physical discomfort, and interference in "domestic, occupational and interpersonal functioning" (2,3). Significant advances in our understanding of the complex pathophysiological mechanisms that drive the condition have led to great improvements in our ability to develop targeted therapies for the condition (1). It is important to recognise that the data available to support the safety and efficacy of these treatments is largely derived from randomised clinical trials, reflecting only the data collected from the trial population during the clinical trial or in its extension phase, and may not be reflective of the expected outcomes for the general population (2). Knowledge of the long-term outcomes of treatment with biologic agents, after the completion of clinical trials and their extension periods, is also lacking (2), and the real-world outcomes for patients who continue these treatments after trials is an area of interest. We aim to develop a case series of Australian adult patients with moderate-to-severe chronic plaque psoriasis who were enrolled in phase 3 clinical trials for bimekizumab, a humanised monoclonal IgG1 antibody targeting IL-17A and IL-17F, to assess the impact that enrolment on this study had on their quality of life, and to follow up their outcomes after their clinical trial was completed and treatment with bimekizumab was continued through compassionate access. Ideally, though this project we will enhance our understanding of the impact that this treatment had on the quality of life for these patients, assess for adverse effects, treatment compliance and long-term outcomes for this group of patients, within the Australian context. Background: The development of psoriatic lesions as a paradoxical adverse effect related to anti-tumour necrosis factor alpha (TNFα) agents has been increasingly reported. The mechanism and determinants of this response remains unclear and of non-consensual management. Case Report: 49 years old female patient, smoker, with diagnosis of severe Crohn's disease, had been using adalimumab for 7 months and then started with pustular lesions on the palms and soles. No personal history of any previous skin disease. An incisional biopsy of a palmar lesion was performed, with histopathology showing compact orthokeratosis, parakeratosis, hypogranulosis, regular acanthosis with subcorneal pustule and perivascular inflammatory infiltrate with the participation of neutrophils. Absence of fungal structures. Considering the severity of the underlying condition, it was decided not to suspend the therapy. The patient had an unsatisfactory response to topical treatment with corticoids, calcipotriol and tar derivatives. However, it evolved with sustained improvement after phototherapy with narrowband ultraviolet B treatment was associated.

Adalimumab-induced palmoplantar pustular psoriasis in a patient with Crohn's disease with good response to phototherapy: Case report
Discussion: Anti-TNFα agents are an effective treatment for many inflammatory conditions, including infammatory bowel disease and psoriasis. It is suggested that most of the patients with paradoxically induced psoriatic lesions can be conducted without the suspension of the therapy, with conventional treatment for psoriasis with early association of phototherapy and systemic options in more extensive cases and pustular psoriasis. The decision to discontinue or change the biological agent is not consensual. Severe, erythrodermic, resistant presentations or presentations that significantly affect quality of life are indications for discontinuing therapy.