Impact of the first wave of the COVID-19 pandemic on the treatment of psoriasis with systemic therapies in France: Results from the PSOBIOTEQ cohort.

BACKGROUND: The nature of the COVID-19 pandemic led to concerns among patients and physicians about the potential impact of immunosuppressive treatments for chronic diseases such as psoriasis on the risk of severe COVID-19. OBJECTIVES: To describe treatment modifications and determine the incidence of COVID-19 infection among psoriasis patients during the first wave of the pandemic, and identify the factors associated with these events. METHODS: Data from PSOBIOTEQ cohort relating to the first COVID-19 wave in France (March to June, 2020), as well as a patient-centred COVID-19 questionnaire, were used to evaluate the impact of lockdown on changes (discontinuations, delays or reductions) in systemic therapies, and to determine the incidence of COVID-19 cases among these patients. Logistic regression models were used to assess associated factors. RESULTS: Among the 1751 respondents (89.3%), 282 patients (16.9%) changed their systemic treatment for psoriasis, with 46.0% of these changes being initiated by the patients themselves. Patients were more likely to experience psoriasis flare-ups during the first wave if they changed their treatment during this period (58.7% vs 14.4%; P < 0.0001). Changes to systemic therapies were less frequent among patients with cardiovascular diseases (P < 0.001), and those aged ≥ 65 years (P = 0.02). Overall, 45 patients (2.9%) reported having COVID-19, and eight (17.8%) required hospitalization. Risk factors for COVID-19 infection were close contact with a positive case (P < 0.001) and living in a region with a high incidence of COVID-19 (P < 0.001). Factors associated with a lower risk of COVID-19 were avoiding seeing a physician (P = 0.002), systematically wearing a mask during outings (P = 0.011) and being a current smoker (P = 0.046). CONCLUSIONS: Discontinuation of systemic psoriasis treatments during the first COVID-19 wave (16.9%) - mainly decided by patients themselves (46.0%) - was associated with a higher incidence of disease flares (58.7% vs 14.4%). This observation and factors associated with a higher risk of COVID-19 highlight the need to maintain and adapt patient-physician communication during health crises according to patient profiles, with the aim of avoiding unnecessary treatment discontinuations and ensuring that patients are informed about the risk of infection and the importance of complying with hygiene rules.

Long-term safety of risankizumab from 17 clinical trials in patients with moderate-to-severe plaque psoriasis.

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.

Palmoplantar pustulosis and acrodermatitis continua of Hallopeau: demographic and clinical comparative study in a large multicentre cohort.

BACKGROUND: Acral pustular disease within the pustular psoriasis/psoriasis-like spectrum mainly includes palmoplantar pustulosis (PPP) and acrodermatitis continua of Hallopeau (ACH). Scarce data argue for a distinction between these two entities, but no study has compared the clinical and epidemiologic characteristics of ACH and PPP. OBJECTIVES: We aimed to perform a comparative description of the epidemiological and clinical characteristics of PPP and ACH in a multicentre retrospective cohort. METHODS: In this multicentre national retrospective cohort study, we compared the epidemiological characteristics, comorbidities and psoriasis characteristics of patients with PPP and ACH. RESULTS: A total of 234 patients were included: 203 (87%) with PPP, 18 (8%) with ACH and 13 (6%) with both, according to 2017 ERASPEN criteria. As compared with ACH, PPP was associated with female sex, smoking activity and higher median BMI (P = 0.01, P = 0.02 and P = 0.05 respectively). A family background of psoriasis was more frequent in PPP than ACH. Age of onset of palmoplantar disease was similar between PPP and ACH patients, median age 44 and 48 years respectively. Peripheral joint inflammatory involvement was the only rheumatic disease associated with ACH. The association with another psoriasis type was similar in PPP and ACH (57.6% and 61.1% respectively). CONCLUSION: Our study confirms in a large PPP cohort the predominance of females and a high prevalence of smoking and elevated body mass index but also shows an association of these features in PPP as compared with ACH. In addition, it highlights peripheral arthritis as the only arthritis endotype associated with ACH. Increased knowledge of the immunogenetic backgrounds underlying these two entities is warranted to better stratify pustular psoriasis or psoriasis-like entities for precision medicine.

Switches between biologics in patients with moderate-to-severe psoriasis: results from the French cohort PSOBIOTEQ.

BACKGROUND: Biologics are the cornerstone of treatment of patients with moderate-to-severe plaque psoriasis and switches between biologics are frequently needed to maintain clinical improvement over time. OBJECTIVES: The main purpose of this study was to describe precisely switches between biologics and how their pattern changed over time with the recent availability of new biologic agents. METHODS: We included patients receiving a first biologic agent in the Psobioteq multicenter cohort of adults with moderate-to-severe psoriasis receiving systemic treatment. We described switches between biologics with chronograms, Sankey and Sunburst diagrams, assessed cumulative incidence of first switch by competing risks survival analysis and reasons for switching. We assessed the factors associated with the type of switch (intra-class - i.e. within the same therapeutic class - vs. inter-class) in patients switching from a TNF-alpha inhibitor using multivariate logistic regression. RESULTS: A total of 2153 patients was included. The cumulative incidence of switches from first biologic was 34% at 3 years. Adalimumab and ustekinumab were the most prescribed biologic agents as first and second lines of treatment. The main reason for switching was loss of efficacy (72%), followed by adverse events (11%). Patients receiving a TNF-alpha inhibitor before 2016 mostly switched to ustekinumab, whereas those switching in 2016 or after mostly switched to an IL-17 inhibitor. Patients switching from a first-line TNF-alpha inhibitor before 2016 were more likely to switch to another TNF-alpha inhibitor compared with patients switching since 2018. Patients switching from etanercept were more likely to receive another TNF-alpha inhibitor rather than another therapeutic class of bDMARD compared with patients switching from adalimumab. CONCLUSION: This study described the switching patterns of biologic treatments and showed how they changed over time, due to the availability of the new biologic agents primarily IL-17 inhibitors.

Children with psoriasis and COVID-19: factors associated with an unfavourable COVID-19 course, and the impact of infection on disease progression (Chi-PsoCov registry).

BACKGROUND: The COVID-19 pandemic has raised questions regarding the management of chronic skin diseases, especially in patients on systemic treatments. Data concerning the use of biologics in adults with psoriasis are reassuring, but data specific to children are missing. Moreover, COVID-19 could impact the course of psoriasis in children. OBJECTIVES: The aim of this study was therefore to assess the impact of COVID-19 on the psoriasis of children, and the severity of the infection in relation to systemic treatments. METHODS: We set up an international registry of paediatric psoriasis patients. Children were included if they were under 18 years of age, had a history of psoriasis, or developed it within 1 month of COVID-19 and had COVID-19 with or without symptoms. RESULTS: One hundred and twenty episodes of COVID-19 in 117 children (mean age: 12.4 years) were reported. The main clinical form of psoriasis was plaque type (69.4%). Most children were without systemic treatment (54.2%); 33 (28.3%) were on biologic therapies, and 24 (20%) on non-biologic systemic drugs. COVID-19 was confirmed in 106 children (88.3%) and 3 children had two COVID-19 infections each. COVID-19 was symptomatic for 75 children (62.5%) with a mean duration of 6.5 days, significantly longer for children on non-biologic systemic treatments (P = 0.02) and without systemic treatment (P = 0.006) when compared with children on biologics. The six children who required hospitalization were more frequently under non-biologic systemic treatment when compared with the other children (P = 0.01), and particularly under methotrexate (P = 0.03). After COVID-19, the psoriasis worsened in 17 cases (15.2%). Nine children (8%) developed a psoriasis in the month following COVID-19, mainly a guttate form (P = 0.01). DISCUSSION: Biologics appear to be safe with no increased risk of severe form of COVID-19 in children with psoriasis. COVID-19 was responsible for the development of psoriasis or the worsening of a known psoriasis for some children.

Type I interferon response and vascular alteration in chilblain-like lesions during the COVID-19 outbreak.

BACKGROUND: The outbreak of chilblain-like lesions (CLL) during the COVID-19 pandemic has been reported extensively, potentially related to SARS-CoV-2 infection, yet its underlying pathophysiology is unclear. OBJECTIVES: To study skin and blood endothelial and immune system activation in CLL in comparison with healthy controls and seasonal chilblains (SC), defined as cold-induced sporadic chilblains occurring during 2015 and 2019 with exclusion of chilblain lupus. METHODS: This observational study was conducted during 9-16 April 2020 at Saint-Louis Hospital, Paris, France. All patients referred with CLL seen during this period of the COVID-19 pandemic were included in this study. We excluded patients with a history of chilblains or chilblain lupus. Fifty patients were included. RESULTS: Histological patterns were similar and transcriptomic signatures overlapped in both the CLL and SC groups, with type I interferon polarization and a cytotoxic-natural killer gene signature. CLL were characterized by higher IgA tissue deposition and more significant transcriptomic activation of complement and angiogenesis factors compared with SC. We observed in CLL a systemic immune response associated with IgA antineutrophil cytoplasmic antibodies in 73% of patients, and elevated type I interferon blood signature in comparison with healthy controls. Finally, using blood biomarkers related to endothelial dysfunction and activation, and to angiogenesis or endothelial progenitor cell mobilization, we confirmed endothelial dysfunction in CLL. CONCLUSIONS: Our findings support an activation loop in the skin in CLL associated with endothelial alteration and immune infiltration of cytotoxic and type I IFN-polarized cells leading to clinical manifestations.

Risk-mitigating behaviours in people with inflammatory skin and joint disease during the COVID-19 pandemic differ by treatment type: a cross-sectional patient survey.

BACKGROUND: Registry data suggest that people with immune-mediated inflammatory diseases (IMIDs) receiving targeted systemic therapies have fewer adverse coronavirus disease 2019 (COVID-19) outcomes compared with patients receiving no systemic treatments. OBJECTIVES: We used international patient survey data to explore the hypothesis that greater risk-mitigating behaviour in those receiving targeted therapies may account, at least in part, for this observation. METHODS: Online surveys were completed by individuals with psoriasis (globally) or rheumatic and musculoskeletal diseases (RMDs) (UK only) between 4 May and 7 September 2020. We used multiple logistic regression to assess the association between treatment type and risk-mitigating behaviour, adjusting for clinical and demographic characteristics. We characterized international variation in a mixed-effects model. RESULTS: Of 3720 participants (2869 psoriasis, 851 RMDs) from 74 countries, 2262 (60·8%) reported the most stringent risk-mitigating behaviour (classified here under the umbrella term 'shielding'). A greater proportion of those receiving targeted therapies (biologics and Janus Kinase inhibitors) reported shielding compared with those receiving no systemic therapy [adjusted odds ratio (OR) 1·63, 95% confidence interval (CI) 1·35-1·97]. The association between targeted therapy and shielding was preserved when standard systemic therapy was used as the reference group (OR 1·39, 95% CI 1·23-1·56). Shielding was associated with established risk factors for severe COVID-19 [male sex (OR 1·14, 95% CI 1·05-1·24), obesity (OR 1·37, 95% CI 1·23-1·54), comorbidity burden (OR 1·43, 95% CI 1·15-1·78)], a primary indication of RMDs (OR 1·37, 95% CI 1·27-1·48) and a positive anxiety or depression screen (OR 1·57, 95% CI 1·36-1·80). Modest differences in the proportion shielding were observed across nations. CONCLUSIONS: Greater risk-mitigating behaviour among people with IMIDs receiving targeted therapies may contribute to the reported lower risk of adverse COVID-19 outcomes. The behaviour variation across treatment groups, IMIDs and nations reinforces the need for clear evidence-based patient communication on risk-mitigation strategies and may help inform updated public health guidelines as the pandemic continues.

Out-of-pocket expenditures in France to manage psoriasis in adult patients: results from an observational, cross-sectional, non-comparative, multicentre study.

BACKGROUND: In 2018 in France, overall mean health-related out-of-pocket (OOP) expenditures were 214.00€/year/patient. AIM: To evaluate OOP expenditures for psoriasis patients in France. METHODOLOGY: Observational, cross-sectional, non-comparative, multicentre study in 3000 patients with clinically confirmed psoriasis who responded to a specific digital questionnaire collecting demographic and socio-economic characteristics, assessing the 3 domains (severity, psychosocial impact and past history and interventions) of the patient's Simplified Psoriasis Index (sa-SPI) and expenditures to manage psoriasis, including OOP. Multivariate linear regression was conducted to search for factors associated with higher OOP. RESULTS: In total, 2681 patients completed the questionnaire and, of those, 2562 provided clinically validated data. Overall, 60% were women; the mean age was 49.4 ± 14.8 years. 30% of the patients declared that they suffered from psoriatic arthritis. The final mean sa-SPI core was 10.86 ± 9.70. Of these 2562 patients, 243 (9.5%) had severe, 442 (17.3%) moderate and 1877 (73.3%) mild psoriasis. In addition, 932 (36.4%) patients reported facial involvement, 724 (28.25%) genital impairment and 1124 (43.8%) lesions on the limbs. Mean OOP expenditures to manage psoriasis per patient were 531.00€, 439.74€ ± 939.85€ for patients with mild, 791.06€ ± 1367.67€ with moderate and 1077.64€ ± 1680.14€ for patients with severe psoriasis. For patients with psoriasis in the genital area, the median amount of expenditures (251.17€; CI95% [138.35;363.99]) was significantly higher than that for the face (183.85€; CI95% [78.76;288.94]) or limbs (199.96€; CI95% [93.77;306.15); (P < 0.001). More than 90% of the patients had OOP expenditures for over-the-counter products (97.5%) and alternative care (92.0%), especially for emollients and/or hydrating products. CONCLUSION: In France, in 2019, OOP expenditures to manage psoriasis were on average more than twice as high as the overall mean health-related OOP expenditures estimated by the French Health Agency in 2018. These results should lead health authorities to review certain standards of healthcare reimbursement.

Efficacy and safety of TNF blockers and of ustekinumab in palmoplantar pustulosis and in acrodermatitis continua of Hallopeau.

BACKGROUND: Palmoplantar pustulosis (PPP) and acrodermatitis continua of Hallopeau (ACH) are rare variants of psoriasis. Knowledge of the efficacy of biologics is scarce. OBJECTIVES: To evaluate the real-life efficacy of tumour necrosis factor blockers and ustekinumab in PPP and in ACH. METHODS: A multicentre retrospective descriptive study was conducted in 19 dermatology departments, including all patients with PPP or ACH seen from 2014 to 2016 who received one of the studied biologics. The data were collected by a standardized document. Factors associated with complete clearance (CC) were analysed by multivariate analysis, estimating odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Among 92 patients included, 50 received adalimumab, 44 ustekinumab, 36 etanercept and 31 infliximab. Improvement and CC were observed in 83.9% and 20.0% patients receiving infliximab, 75.0% and 38.6% ustekinumab, 57.1% and 20.0% etanercept and 60.4% and 29.2% adalimumab. We found no significant difference in CC rates or duration of treatment among the biological treatments (P = 0.18 and P = 0.10, respectively). On multivariate analysis, CC with etanercept was associated with the ACH form and not smoking [OR = 9.5 (95% CI 1.1-82.7), P = 0.04 and 0.1 (0.01-0.9), P = 0.04]; with ustekinumab, male sex and absence of obesity [6.0 (1.3-28.6), P = 0.02 and 4.7 (1.0-22.7), P = 0.05]; with adalimumab, the ACH form [11.9 (2.7-52.3), P = 0.001]; and with infliximab, obesity [5.6 (1.1-29.4), P = 0.04]. CONCLUSIONS: We found no difference in efficacy between TNF blockers and ustekinumab and among the three different TNF blockers in real life for PPP or ACH, which reveals the heterogeneity of clinical response to biologics in pustular psoriasis as compared with plaque psoriasis.

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

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

Benefit-risk profile of tofacitinib in patients with moderate-to-severe chronic plaque psoriasis: pooled analysis across six clinical trials.

BACKGROUND: Although existing psoriasis treatments are effective and well tolerated in many patients, there is still a need for new effective targeted treatment options. Tofacitinib is an oral Janus kinase inhibitor that has been investigated in patients with moderate-to-severe chronic plaque psoriasis. OBJECTIVES: To consider the benefits and risks of tofacitinib in patients with moderate-to-severe psoriasis. METHODS: Data were pooled from one phase II, four phase III and one long-term extension study comprising 5204 patient-years of tofacitinib treatment. Efficacy end points included patients achieving Physician's Global Assessments of 'clear' or 'almost clear', ≥ 75% and ≥ 90% reduction in Psoriasis Area and Severity Index (coprimary end points) and improvements in Dermatology Life Quality Index score, Hospital Anxiety and Depression Scale depression score and Itch Severity Item score, at weeks 16 and 52. Safety data were summarized for 3 years of tofacitinib exposure. RESULTS: Tofacitinib 5 and 10 mg twice daily (BID) showed superiority over placebo for all efficacy end points at week 16, with response maintained for 52 weeks of continued treatment. Tofacitinib improved patients' quality of life and was well tolerated. Rates of safety events of interest (except herpes zoster) were similar to those in the published literature and healthcare databases for other systemic psoriasis therapies. Tofacitinib 10 mg BID demonstrated greater efficacy than 5 mg BID. CONCLUSIONS: Tofacitinib has a benefit-risk profile in moderate-to-severe psoriasis consistent with that of other systemic treatments.

Pustular psoriasis and related pustular skin diseases.

Patients with pustular psoriasis or related pustular diseases may have genetic abnormalities impairing the function of key players of the innate skin immune system. Recently, identification of these abnormalities has changed the paradigm of several of these diseases. These include generalized pustular psoriasis, palmoplantar pustular psoriasis and acrodermatitis continua of Hallopeau, and also drug-induced acute exanthematous generalized pustular eruption. Identified mutations in IL36RN, CARD14 and AP1S3 in different groups of patients lead to enhanced inflammatory cascade in several cellular subtypes including keratinocytes, and to the recruitment and activation of neutrophils and macrophages. These insights have unveiled pathophysiological features that shift the existing paradigms and emphasize the autoinflammatory nature of skin pustular disorders. They also highlight the crucial role of the innate immune system across entities belonging to the psoriasis disease spectrum, allowing identification of new appealing therapeutic targets.

Trends in hospitalization rates for psoriasis flares since the introduction of biologics: a time series in France between 2005 and 2015.

BACKGROUND: In the late 2000s, the introduction of biologics transformed the prognosis for patients with moderate-to-severe psoriasis. We hypothesized that treatment with biologics may associate with a reduction in the hospitalization rate for psoriasis flares. OBJECTIVE: To analyse changes over time in the hospitalization rate for psoriasis flares. METHODS: We included inpatient stays in any of nine French hospitals between 2005 and 2015 for a psoriasis flare, as documented in the national inpatient database. In two centres, we also analysed data from the individual patients' electronic medical records. RESULTS: A total of 3572 stays were included. The introduction of biologics was not associated with a decrease in the number of hospitalizations for a psoriasis flare; on the contrary, we observed a non-significant increase in the number of hospitalizations (13 hospitalizations for psoriasis flares per quarter per 10 000 beds). In the two-centre study, the introduction of biologics was associated with a significant increase in the hospitalization of patients receiving topical treatments only (520 hospitalizations per year per 10 000 beds) and those with a first psoriasis flare. CONCLUSION: The number of hospitalizations for a psoriasis flare tended to increase between 2005 and 2015. The availability of additional treatment options might have increased patient demand and/or broadened the indications in clinical practice.

A Topical Treatment Optimization Programme (TTOP) improves clinical outcome for calcipotriol/betamethasone gel in psoriasis: results of a 64-week multinational randomized phase IV study in 1790 patients (PSO-TOP).

BACKGROUND: Around two-thirds of patients with psoriasis do not adhere to topical treatment. The Topical Treatment Optimization Programme (TTOP), a five-element tool, includes guidance for the conversation between dermatologists/nurses and patients, patient information material, telephone/e-mail helpdesks and treatment reminders. It has been developed by patients and dermatologists to help increase adherence to treatment in psoriasis. OBJECTIVES: To compare TTOP with standard of care ('non-TTOP') within a large European investigator-initiated study, PSO-TOP (clinicaltrials.gov NCT01587755). METHODS: Patients with mild-to-moderate psoriasis received calcipotriol/betamethasone dipropionate gel as standardized study medication and were randomized 1 : 1 to either TTOP or non-TTOP management. Study medication was applied once daily for 8 weeks followed by 'as needed' application for an additional 56 weeks. Response was defined as a Physician's Global Assessment (PGA) of 'clear' or 'almost clear'. RESULTS: In 1790 patients (full analysis set), response rates after 8 weeks (primary objective) were significantly higher for TTOP (36·3%) than for non-TTOP (31·3%, P = 0·0267). Better clinical outcome was accompanied by higher rates of patients feeling well informed about their skin condition, treatment and other factors related to adherence, but the Dermatology Life Quality Index was not statistically different. TTOP patients regarded the structured one-to-one conversations with their dermatologist/nurse as the most important element of TTOP. CONCLUSIONS: Patients randomized to the TTOP intervention had a better clinical response than patients receiving standard of care. Improved communication between the healthcare provider and patient might be an important element in increasing adherence to topical therapy in psoriasis.

Clinical similarity of the biosimilar ABP 501 compared with adalimumab after single transition: long-term results from a randomized controlled, double-blind, 52-week, phase III trial in patients with moderate-to-severe plaque psoriasis.

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.

Infections from seven clinical trials of ixekizumab, an anti-interleukin-17A monoclonal antibody, in patients with moderate-to-severe psoriasis.

BACKGROUND: Infections are associated with biological therapies in psoriasis. OBJECTIVES: To summarize the incidence of infections in patients with moderate-to-severe psoriasis treated with ixekizumab, an anti-interleukin-17A monoclonal antibody. METHODS: Infections are summarized from an integrated database of seven controlled and uncontrolled ixekizumab psoriasis trials. Data are presented from placebo-controlled induction (weeks 0-12; UNCOVER-1, UNCOVER-2 and UNCOVER-3) and maintenance periods (weeks 12-60; UNCOVER-1 and UNCOVER-2), and all patients exposed to ixekizumab pooled from all seven trials. Comparisons with etanercept were made during the induction period of two trials (UNCOVER-2 and UNCOVER-3). Incidence and exposure-adjusted incidence rates (IRs) per 100 patient-years (PYs) are reported. RESULTS: Overall, 4209 patients were treated with ixekizumab (6480 PY). During induction (weeks 0-12), overall infection rates were higher in patients treated with ixekizumab (27%) vs. placebo (23%, P < 0·05); however, specific infection rates were comparable overall across treatment groups. IRs of infections did not increase with longer-term exposure. For all patients treated with ixekizumab (all seven trials), the incidence of serious infections was low (2%, IR 1·3). Candida infections, including eight cases of oesophageal candidiasis, were adequately managed with antifungal therapy, were noninvasive and did not lead to discontinuation. CONCLUSIONS: Overall, infections occurred in a higher percentage of patients treated with ixekizumab vs. placebo during the first 12 weeks of treatment; however, specific infection rates were comparable overall across treatment groups. Incidences of serious infections were low and similar across treatment groups.

A European subset analysis from the population-based Multinational Assessment of Psoriasis and Psoriatic Arthritis shows country-specific features: results from psoriasis patients in Spain.

BACKGROUND: The Multinational Assessment of Psoriasis and Psoriatic Arthritis (MAPP) survey data were not analysed to account for cultural and healthcare system differences across European countries (EC). OBJECTIVE: To utilize MAPP data to characterize psoriasis in Spanish patients, including severity assessment and Dermatology Life Quality Index (DLQI). METHODS: The MAPP survey was conducted between June and August 2012. This analysis included 1700 patients with self-reported psoriasis (without psoriatic arthritis) from France (n = 349), Germany (n = 311), Italy (n = 359), Spain (n = 354) and the United Kingdom (n = 327). RESULTS: Patients from Spain vs. other EC self-reported higher mean body mass index (26.9 vs. 25.6, P ≤ 0.001), lower prevalence of depression (6% vs. 12%, P = 0.002) and higher mean self-perceived psoriasis severity at its worst (5.92 vs. 5.33, P < 0.001) despite lower estimated body-surface-area involvement. Overall, patients from Spain vs. other EC had lower mean global DLQI scores (4.70 vs. 6.06, P = 0.001) and lower mean scores for each DLQI dimension [all P < 0.001, except leisure (P = 0.002), treatment (P = 0.002), and work and school (P = 0.005)]. Higher DLQI values were inversely associated with age and directly correlated with perceived severity. Palmoplantar, nail and scalp psoriasis were reported less frequently in Spanish patients (P = 0.026) and were associated with higher DLQI values (P < 0.01). Spanish patients were more likely to have seen multiple healthcare providers (HCPs; P < 0.001) and achieve therapeutic goals (P < 0.001), but current treatments were similar to patients in other EC. CONCLUSIONS: In the MAPP survey, Spanish patients differed from other EC in several characteristics, including comorbidities, extent and distribution of psoriasis lesions, perception of severity and impact on quality of life. Their perception of psoriasis severity was higher despite a lower estimated extent, and DLQI scores were significantly lower. Spanish patients had more HCP visits and a higher rate of therapeutic goal achievement. These differences might be attributed to cultural factors, phenotypical variation and differences in HCP access.

The role of IL-23 and the IL-23/TH 17 immune axis in the pathogenesis and treatment of psoriasis.

Psoriasis is a chronic, immune-mediated disease affecting more than 100 million people worldwide and up to 2.2% of the UK population. The aetiology of psoriasis is thought to originate from an interplay of genetic, environmental, infectious and lifestyle factors. The manner in which genetic and environmental factors interact to contribute to the molecular disease mechanisms has remained elusive. However, the interleukin 23 (IL-23)/T-helper 17 (TH 17) immune axis has been identified as a major immune pathway in psoriasis disease pathogenesis. Central to this pathway is the cytokine IL-23, a heterodimer composed of a p40 subunit also found in IL-12 and a p19 subunit exclusive to IL-23. IL-23 is important for maintaining TH 17 responses, and levels of IL-23 are elevated in psoriatic skin compared with non-lesional skin. A number of agents that specifically inhibit IL-23p19 are currently in development for the treatment of moderate-to-severe plaque psoriasis, with recent clinical trials demonstrating efficacy with a good safety and tolerability profile. These data support the role of this cytokine in the pathogenesis of psoriasis. A better understanding of the IL-23/TH 17 immune axis is vital and will promote the development of additional targets for psoriasis and other inflammatory diseases that share similar genetic aetiology and pathogenetic pathways.