Deucravacitinib in moderate-to-severe plaque psoriasis: Pooled safety and tolerability over 52 weeks from two phase 3 trials (POETYK PSO-1 and PSO-2).

BACKGROUND: Two phase 3 trials, POETYK PSO-1 and PSO-2, previously established the efficacy and overall safety of deucravacitinib, an oral, selective, allosteric tyrosine kinase 2 (TYK2) inhibitor, in plaque psoriasis. OBJECTIVES: To further assess the safety of deucravacitinib over 52 weeks in the pooled population from these two trials. METHODS: Pooled safety data were evaluated from PSO-1 and PSO-2 in which patients with moderate-to-severe plaque psoriasis were randomized 1:2:1 to receive oral placebo, deucravacitinib or apremilast. RESULTS: A total of 1683 patients were included in the pooled analysis. Adverse event (AE) incidence rates were similar in each treatment group, serious AEs were low and balanced across groups, and discontinuation rates were lower with deucravacitinib versus placebo or apremilast. No new safety signals emerged with longer deucravacitinib treatment. Exposure-adjusted incidence rates of AEs of interest with placebo, deucravacitinib and apremilast, respectively, were as follows: serious infections (0.8/100 person-years [PY], 1.7/100 PY, and 1.8/100 PY), major adverse cardiovascular events (1.2/100 PY, 0.3/100 PY, and 0.9/100 PY), venous thromboembolic events (0, 0.2/100 PY, and 0), malignancies (0, 1.0/100 PY and 0.9/100 PY), herpes zoster (0.4/100 PY, 0.8/100 PY, and 0), acne (0.4/100 PY, 2.9/100 PY, and 0) and folliculitis (0, 2.8/100 PY, and 0.9/100 PY). No clinically meaningful changes from baseline in mean levels, or shifts from baseline to CTCAE grade ≥3 abnormalities, were reported in laboratory parameters with deucravacitinib. CONCLUSIONS: Deucravacitinib was well-tolerated with acceptable safety over 52 weeks in patients with psoriasis.

A randomized, double-blind, placebo-controlled phase II study to evaluate the efficacy and safety of ivarmacitinib (SHR0302) in adult patients with moderate-to-severe alopecia areata.

BACKGROUND: Alopecia areata (AA) is a CD8+ T cell-mediated autoimmune disease characterized by nonscarring hair loss. Ivarmacitinib, which is a selective oral Janus kinase 1 inhibitor, may interrupt certain cytokine signaling implicated in the pathogenesis of AA. OBJECTIVE: To evaluate the efficacy and safety of ivarmacitinib in adult patients with AA who have ≥25% scalp hair loss. METHODS: Eligible patients were randomized 1:1:1:1 to receive ivarmacitinib 2, 4, or 8 mg once daily or placebo for 24 weeks. The primary end point was the percentage change from baseline in the Severity of Alopecia Tool score at week 24. RESULTS: A total of 94 patients were randomized. At week 24, the least squares mean difference in the percentage change from baseline in the Severity of Alopecia Tool score for ivarmacitinib 2, 4, and 8 mg and placebo groups were -30.51% (90% CI, -45.25, -15.76), -56.11% (90% CI, -70.28, -41.95), -51.01% (90% CI, -65.20, -36.82), and -19.87% (90% CI, -33.99, -5.75), respectively. Two serious adverse events-follicular lymphoma and COVID-19 pneumonia-were reported. LIMITATIONS: A small sample size limits the generalizability of the results. CONCLUSION: Treatment with ivarmacitinib 4 and 8 mg doses in patients with moderate and severe AA for 24 weeks was efficacious and generally tolerated.

Malignancy rates through 5 years of follow-up in patients with moderate-to-severe psoriasis treated with guselkumab: Pooled results from the VOYAGE 1 and VOYAGE 2 trials.

BACKGROUND: Malignancy risk surveillance among patients receiving long-term immunomodulatory psoriasis treatments remains an important safety objective. OBJECTIVE: To report malignancy rates in patients with moderate-to-severe psoriasis treated with guselkumab for up to 5 years versus general and psoriasis patient populations. METHODS: Cumulative rates of malignancies/100 patient-years (PY) were evaluated in 1721 guselkumab-treated patients from VOYAGE 1 and 2. Malignancy rates (excluding nonmelanoma skin cancer [NMSC]) were compared with rates in the Psoriasis Longitudinal Assessment and Registry. Standardized incidence ratios comparing malignancy rates (excluding NMSC and cervical cancer in situ) between guselkumab-treated patients and the general US population using Surveillance, Epidemiology, and End Results data were calculated, adjusting for age, sex, and race. RESULTS: Of 1721 guselkumab-treated patients (>7100 PY), 24 had NMSC (0.34/100PY; basal:squamous cell carcinoma ratio, 2.2:1), and 32 had malignancies excluding NMSC (0.45/100PY). For comparison, the malignancy rate excluding NMSC was 0.68/100PY in the Psoriasis Longitudinal Assessment and Registry. Malignancy rates (excluding NMSC/cervical cancer in situ) in guselkumab-treated patients were consistent with those expected in the general US population (standardized incidence ratio = 0.93). LIMITATIONS: Inherent imprecision in determining malignancy rates. CONCLUSIONS: In patients treated with guselkumab for up to 5 years, malignancy rates were low and generally consistent with rates in general and psoriasis patient populations.

Preliminary efficacy and safety analysis: 12-month results in 83 patients using a novel approach of widefield radiation therapy for extensive skin field cancerization with or without keratinocyte cancers.

PURPOSE: Evaluate the use of widefield radiation therapy (RT) in the management of extensive skin field cancerization (ESFC) with/without keratinocyte cancer (KC). METHODS: The National Dermatology Radiation Oncology Registry is a multidisciplinary collaboration (dermatologists and radiation oncologists). It captures disease description, prior therapies, radiation prescription, clinical effect, skin cosmesis scores, and toxicity data. This analysis included 12-month follow-up data on 89 treated fields from a subset of 83 patients. RESULTS: Clinical success (>90% field clearance) was 96% (ESFC, n = 63) and 88% (ESFC with KC, n = 26). Complete lesion response was seen in 96% of evaluable (n = 25) ESFC with KC. Recurrence (4/89 [5%]) and appearance of new lesions (10/89 [11%]) were minimal. Cosmetic outcome was excellent/good in 98% ESFC and 96% ESFC with KC. Grade 1-2 acute radiation dermatitis occurred in up to 80% of treated fields. The frequency of Grade 3 acute skin toxicities was low. CONCLUSIONS: Registry data demonstrate the potential for widefield RT to treat patients with significant skin pathology who have exhausted other therapies and require durable, minimally invasive treatment options. At 12 months, observed clinical success rates were higher than those reported for topical interventions for ESFC. Ongoing follow-up is required to determine longer term outcomes.

Method of Assessing Skin Cancerization and KeratosesTM (MASCK™): development and photographic validation in multiple anatomical sites of a novel assessment tool intended for clinical evaluation of patients with extensive skin field cancerization.

BACKGROUND: A range of 'field-directed' treatments is available for the management of extensive skin field cancerization (ESFC), but to date, the only validated objective quantitative tools are limited to assessment of actinic keratoses (AKs) affecting the head. AIMS: To develop a versatile quantitative instrument for objective clinical assessment of ESFC and perform initial internal validation across multiple anatomical zones. METHODS: The study comprised instrument development, pilot testing and instrument refinement and two rounds of reliability and inter-rater validation testing. The study was noninterventional and used a convenience sample of de-identified patient photographs selected based on preset criteria. An expert panel developed the instrument and scoring system via a modified Delphi voting process. A sample of 16 healthcare professionals from multiple specialties undertook the pilot testing, and a panel of seven dermatologists were involved in validation testing. Validation was determined by assessment of overall inter-rater agreement using Gwet chance-corrected agreement coefficients (ACs). RESULTS: The instrument produced, called the Method for Assessing Skin Cancer and Keratoses™ (MASCK™), comprises the Skin Field Cancerization Index (SFCIndex), derived from area of skin involvement and AKs (number and thickness), a global assessment score and a cancer-in-zone score, and uses Likert scales for quantitative scoring. The SFCIndex is a composite score comprising the number and thickness of AKs multiplied by area of skin involvement. ACs for the SFCIndex components, the overall SFCIndex score and the global assessment score were > 0.80 (rated 'almost perfect') while the AC for the cancer-in-zone metric was lower (0.33, rated 'fair'). Internal consistency was demonstrated via positive correlation between the overall SFCIndex score and the global assessment score. CONCLUSIONS: Our study found near-perfect agreement in inter-rater reliability when using MASCK to assess the severity of ESFC in multiple anatomical sites. Further validation of this novel instrument is planned to specifically assess its reliability, utility and feasibility in clinical practice.

Combination treatment with monoclonal antibodies: Secukinumab, benralizumab and dupilumab for the combined management of psoriasis and severe asthma.

Biological disease-modifying agents have increasingly become available for the effective treatment of both cutaneous and non-cutaneous inflammatory conditions. We report a case of a woman treated successfully for psoriasis and psoriatic arthritis with the IL-17 inhibitor secukinumab whilst simultaneously being treated for severe asthma and nasal polyps, initially with the IL-5 inhibitor benralizumab, followed by dupilumab, a monoclonal antibody that targets the IL-4 receptor alpha subunit which blocks signalling from both IL-4 and IL-13.

Serologic and urinary survey of exposure to Leptospira species in a feral cat population of Prince Edward Island, Canada.

OBJECTIVES: Recent studies show that cats could play an important role in the transmission of Leptospira species. There are few reports of leptospirosis on Prince Edward Island (PEI) and none in cats. The objective of this study was to determine the prevalence of serum antibodies against Leptospira serovars and of Leptospira DNA in the urine of a population of free-roaming cats. METHODS: Paired blood and urine samples were collected from 200 cats brought to a trap-neuter-return program. Antibody titers against six Leptospira serovars (Bratislava, Canicola, Gryppotyphosa, Hardjo, Pomona, Icterohaemorrhagiae) were determined by microscopic agglutination test. PCR was performed on urine samples to identify urine shedding of Leptospira DNA. RESULTS: Antibodies were detected in 20/200 cats (10%) for at least one serovar, with titers ranging from 1:50 to 1:6400 (all serovars tested, except Hardjo). Urine samples of 7/200 cats (3.5%) were PCR-positive. CONCLUSIONS AND RELEVANCE: Feral cats in PEI had a higher than expected exposure to leptospirosis and can shed DNA from pathogenic Leptospira species in urine. Further studies are needed to determine the prevalence of exposure to leptospirosis in other species on PEI and the potential role of feral cats in transmission of the disease.

Management of chronic hand and foot eczema. An Australia/New Zealand Clinical narrative.

Chronic hand/foot eczemas are common, but treatment is often challenging, with widespread dissatisfaction over current available options. Detailed history is important, particularly with regard to potential exposure to irritants and allergens. Patch testing should be regarded as a standard investigation. Individual treatment outcomes and targets, including systemic therapy, should be discussed early with patients, restoring function being the primary goal, with clearing the skin a secondary outcome. Each new treatment, where appropriate, should be considered additive or overlapping to any previous therapy. Management extends beyond mere pharmacological or physical treatment, and requires an encompassing approach including removal or avoidance of causative factors, behavioural changes and social support. To date, there is little evidence to guide sequences or combinations of therapies. Moderately symptomatic patients (e.g. DLQI ≥ 10) should be started on a potent/super-potent topical corticosteroid applied once or twice per day for 4 weeks, with tapering to twice weekly application. If response is inadequate, consider phototherapy, and then a 12-week trial of a retinoid (alitretinoin or acitretin). Second line systemic treatments include methotrexate, ciclosporin and azathioprine. For patients presenting with severe symptomatic disease (DLQI ≥ 15), consider predniso(lo)ne 0.5-1.0 mg/kg/day (or ciclosporin 3 - 5 mg/kg/day) for 4-6 weeks with tapering, and then treating as for moderate disease as above. In non-responders, botulinum toxin and/or iontophoresis, if associated with hyperhidrosis, may sometimes help. Some patients only respond to long-term systemic corticosteroids. The data on sequencing of newer agents, such as dupilumab or JAK inhibitors, are immature.

Prevalence of feline herpesvirus-1, feline calicivirus, Chlamydia felis, and Bordetella bronchiseptica in a population of shelter cats on Prince Edward Island.

The prevalence of the causative agents of feline upper respiratory tract disease (URTD) has been previously documented in many regions worldwide, but has yet to be reported in eastern Canada. The objectives of this study were to determine the prevalence of feline herpesvirus-1 (FHV-1), feline calicivirus (FCV), Chlamydia felis (C. felis), and Bordetella bronchiseptica (B. bronchiseptica) in a population of shelter cats with clinical signs related to URTD on Prince Edward Island, Canada; to compare the prevalence of FHV-1 and FCV as detected by polymerase chain reaction (PCR) and virus isolation (VI) in this population; and lastly, to determine whether factors, such as co-infections, time of year, concurrent feline leukemia virus (FeLV)- or feline immunodeficiency virus (FIV)-positive status, or clinical signs, were associated with prevalence of particular pathogens. Conjunctival, nasal mucosal, and oropharyngeal swabs were collected from 82 cats with clinical signs consistent with URTD. Samples were pooled in transport medium and PCR was used to detect FHV-1, FCV, and C. felis and VI was also used to detect FHV-1 and FCV. A separate swab was submitted for aerobic bacterial culture to detect B. bronchiseptica. Feline herpesvirus-1 (FHV-1) was the most prevalent in this population, followed by C. felis, B. bronchiseptica, and FCV. Of the 4 cats that were positive for B. bronchiseptica, 3 were concurrently positive for FHV-1. All positive B. bronchiseptica cultures were resistant to cefovecin. The prevalence for FHV-1 was lowest in autumn (seasons P < 0.001) and was positively associated with the presence of nasal discharge (P = 0.018) and coughing (P = 0.043).

La prévalence des agents causals de maladies du tractus respiratoire supérieur félin (URTD) a été préalablement documentée dans plusieurs régions du monde mais n'a pas encore été rapportée dans l'est du Canada. Les objectifs de la présente étude étaient de déterminer la prévalence d'herpès virus félin-1 (FHV-1), du calicivirus félin (FCV), de Chlamydia felis et de Bordetella bronchiseptica dans une population de chats de refuge de l'Île-du-Prince-Édouard, Canada avec des signes cliniques reliés au URTD; de comparer la prévalence de FHV-1 et FCV telle que détecter par réaction d'amplification en chaîne par la polymérase (PCR) et l'isolement viral (VI) dans ces populations; et finalement, déterminer si des facteurs, tels que les co-infections, la période de l'année, le statut concomitant positif pour le virus de la leucémie féline (FeLV) ou le virus de l'immunodéficience féline (FIV) ou les signes cliniques étaient associés avec la prévalence d'un agent pathogène en particulier. Des écouvillons de la conjonctive, de la muqueuse nasale et de l'oropharynx furent obtenus de 82 chats avec des signes cliniques compatibles avec URTD. Les échantillons étaient regroupés dans un milieu de transport et la PCR utilisée pour détecter FHV-1, FCV et C. felis et l'isolement viral fut également utilisé pour détecter FHV-1 et FCV. Un écouvillon séparé fut soumis pour culture bactérienne aérobie afin de détecter B. bronchiseptica. Le FHV-1 était le plus prévalent dans cette population, suivi par C. felis, B. bronchiseptica et FCV. Des quatre chats qui étaient positifs pour B. bronchiseptica, trois étaient positifs également pour FHV-1. Tous les isolats de B. bronchiseptica obtenus étaient résistants au céfovecin. La prévalence de FHV-1 était à son plus bas en automne (P < 0,001 pour les saisons) et était associée positivement avec la présence d'écoulement nasal (P = 0,018) et de la toux (P = 0,043).(Traduit par Docteur Serge Messier).

Beyond skin deep: addressing comorbidities in psoriasis.

Psoriasis is a chronic inflammatory disease that is commonly encountered in primary care and is associated with significant morbidity that extends beyond the skin manifestations. Psoriasis is associated with an elevated risk of psoriatic arthritis, cardiovascular disease, obesity, insulin resistance, mental health disorders, certain types of malignancy, inflammatory bowel disease and other immune-related disorders, and hepatic and renal disease. Enhanced recognition of these comorbidities may lead to earlier diagnosis and potentially better overall health outcomes. Psoriatic nail involvement, severe skin disease and obesity are associated with a greater risk of psoriatic arthritis. Individuals with psoriasis should be routinely screened for psoriatic arthritis to allow for early intervention to improve long term prognosis. Life expectancy is reduced in people with psoriasis due to a variety of causes, with cardiovascular disease and malignancy being the most common aetiologies. Psoriasis affects several factors that contribute to worsened quality of life and increased risk of depression and anxiety. Effective therapies are now available that have been shown to concurrently improve skin disease, quality of life and psychiatric symptoms. As the concordance between psychosocial impact and objective disease severity does not always correlate, it is essential to tailor management strategies specifically to the needs of each individual. Cigarette smoking and excess alcohol consumption are among the most important modifiable risk factors that increase the likelihood of psoriasis development and severity of skin disease. This provides a compelling rationale for smoking cessation and limiting alcohol intake in people with psoriasis beyond their traditional harmful health consequences.

Case report: meningitis as a presenting feature of anti-NMDA receptor encephalitis.

BACKGROUND: Meningitis is a very rare atypical presenting feature of anti-NMDA receptor encephalitis. In our case report, we describe an unusual clinical presentation of anti-NMDA receptor encephalitis with a biphasic pattern of meningitis followed by encephalitis and discuss potential mechanisms underlying this presentation. We aim to widen the differential diagnosis to be considered in a patient presenting with clinical meningitis and pyrexia. CASE PRESENTATION: This is a case of a 33-year old Caucasian woman who initially presented with a lymphocytic meningitis attributed to a viral infection. She subsequently developed fluctuating consciousness, agitation, visual hallucinations, dyskinetic movements, a generalized tonic-clonic seizure, and autonomic instability. Investigations revealed a diagnosis of anti-NMDA receptor encephalitis secondary to a previously unidentified ovarian teratoma. She made an excellent recovery with immunotherapy and removal of the teratoma. CONCLUSION: Clinicians should consider autoimmune encephalitides in individuals with meningitis, particularly where extensive investigations fail to identify a causative pathogen and there is rapid development of an encephalitic phenotype.

Maintenance of clinical response and consistent safety profile with up to 3 years of continuous treatment with guselkumab: Results from the VOYAGE 1 and VOYAGE 2 trials.

BACKGROUND: Long-term maintenance treatment is required for patients with psoriasis. OBJECTIVES: To evaluate the efficacy and safety of guselkumab in patients with moderate to severe psoriasis through 3 years of treatment. METHODS: In 2 ongoing, phase 3 trials of guselkumab (VOYAGE 1 and VOYAGE 2), the proportions of patients achieving at least 90% and 100% improvement in the Psoriasis Area and Severity Index (PASI 90 and PASI 100, respectively) and Investigator's Global Assessment (IGA) scores of 0/1 and 0 were summarized for the guselkumab group (including placebo-to-guselkumab crossover). Patients who met treatment failure rules were considered nonresponders. Safety outcomes (rates/100 patient-years [PY]) were evaluated based on data pooled across studies through week 156. RESULTS: Three-year response rates for the guselkumab group in VOYAGE 1 and VOYAGE 2, respectively, were 82.8% and 77.2% for PASI 90, 50.8% and 48.8% for PASI 100, 82.1% and 83.0% for IGA score of 0/1, and 53.1% and 52.9% for IGA score of 0. Safety event rates across studies occurred through week 156 as follows: serious adverse events, 5.68/100 PY; serious infections, 1.15/100 PY; nonmelanoma skin cancers, 0.28/100 PY; malignancies other than nonmelanoma skin cancer, 0.47/100 PY; and major adverse cardiovascular events, 0.28/100 PY. Week 156 and week 100 rates were consistent. LIMITATIONS: There was no comparator arm beyond 1 year. CONCLUSIONS: Guselkumab shows durable efficacy and a consistent safety profile in patients with moderate to severe psoriasis treated for up to 3 years.

Initial assessment of the early arthritis for psoriatic patients diagnostic questionnaire in dermatology clinics in Australia, Korea and China.

OBJECTIVES: To conduct initial assessment of the early arthritis for psoriatic patients (EARP) questionnaire for Australian, Korean and Chinese populations using translated and linguistically validated versions. To measure the proportion of patients with psoriatic arthritis (PsA) among patients with psoriasis who attended dermatology clinics. METHODS: Questionnaires were translated and culturally validated into Australian English, Korean and Chinese. A multicenter, observational, descriptive estimate of the proportion of patients with PsA among patients with psoriasis attending dermatology clinics in Australia, Korea and China was conducted. Initial assessments included evaluations of floor and ceiling effects, internal consistency (using Cronbach's alpha), test-retest reliability (using intraclass coefficient), and correlations between EARP score and rheumatology findings. If the initial EARP score was ≥3, patients were assessed by a rheumatologist for PsA within 3 months of their retest questionnaire. RESULTS: Two hundred and fifty patients participated. Translated EARP questionnaires showed satisfactory internal consistency and test-retest reliability. A potential floor effect was observed for the Chinese and Korean versions. Cronbach's alpha was 0.885 (Australian), 0.776 (Korean) and 0.789 (Chinese), indicating acceptable internal consistency. Intraclass correlation coefficients were 0.89 (Australian), 0.86 (Korean) and 0.87 (Chinese), indicating acceptable test-retest reliability. EARP summary scores had weak to moderate linear correlation with the relevant PsA assessments. Overall, 32 (12.8%) patients were diagnosed with PsA based on Classification for Psoriatic Arthritis (CASPAR) score. CONCLUSION: The Australian, Korean, and Chinese versions of the EARP questionnaire are suitable for the early detection of PsA symptoms in patients with psoriasis by dermatologists working in specialist dermatology clinics. TRIAL REGISTRATION: NCT02470481.

Psoriasis and infection. A clinical practice narrative.

The Australasian Psoriasis Collaboration has developed a clinical practice narrative with respect to the relationship between psoriasis, its treatment and infection. The cutaneous microbiome of patients with psoriasis is different to those without psoriasis, although the significance of this is unclear. Whilst a wide range of microorganisms has been associated with psoriasis (including ß-haemolytic streptococci, Staphylococcus aureus, Porphyromonas gingivalis, Candida albicans, Chlamydia psittaci, human immunodeficiency virus and hepatitis C virus), there is limited evidence that antimicrobial therapy is of direct benefit in preventing flares of psoriasis. Psoriasis is independently associated with an increased risk of serious infection, but the absolute risk is low. The risk of serious infections is further increased with immune-modulatory treatments. The decision whether to, and when to, stop or resume immune-modulatory treatment after a serious infection has occurred depends on risk assessment for that patient, taking into account the infection being treated, the risk of recurrent infection, any interventions that can modify the risk and the need for psoriasis control. Live vaccines (e.g. MMR, varicella, zoster and yellow fever) are generally contraindicated in patients with psoriasis on immune-modulatory agents, but this depends on the degree of immune suppression and individual risk factors. Wound healing in psoriasis is normal. Treatment with infliximab, adalimumab, etanercept, methotrexate and ciclosporin can safely be continued through low-risk surgical procedures. For moderate- and high-risk surgeries, a case-by-case approach should be taken based on the patient's individual risk factors and comorbidities.

Psoriasis and cancer. An Australian/New Zealand narrative.

Patients with psoriasis have an increased risk of cancer, which may be due to impaired immune surveillance, immune modulatory treatments, chronic inflammation and/or co-risk factors such as obesity. The increase in treatment-independent solid cancers, including urinary/bladder cancers, oropharynx/larynx, liver/gallbladder and colon/rectal cancers, seem to be linked to alcohol and smoking. Lung cancer and nonmelanoma skin cancer are also increased in patients with psoriasis. The risk of nonmelanoma skin cancer increases with age and severity of psoriasis. It is also higher in men, particularly for squamous cell carcinoma, which may reflect previous exposure to PUVA and/or ciclosporin. The risk of cutaneous T-cell lymphoma is substantially higher in patients with moderate-to-severe psoriasis. Biologic therapies are independently associated with a slight increase risk of cancer, but this is less than ciclosporin, with the risk confounded by disease severity and other co-risk factors. The risk of cancer from low-dose methotrexate is likely minimal. In contrast, acitretin is likely protective against a variety of solid and haematological malignancies. The data on small molecule therapies such as apremilast are too immature for comment, although no signal has yet been identified. The decision whether to stop psoriasis immune modulatory treatments following a diagnosis of cancer, and when to resume, needs to be considered in the context of the patients' specific cancer. However, there is no absolute need to stop any treatment other than possibly ciclosporin, unless there is a concern over an increased risk of serious infection or drug-drug interaction with cancer-directed therapies, including radiotherapy.

Improvement in Patient-Reported Outcomes (Dermatology Life Quality Index and the Psoriasis Symptoms and Signs Diary) with Guselkumab in Moderate-to-Severe Plaque Psoriasis: Results from the Phase III VOYAGE 1 and VOYAGE 2 Studies.

BACKGROUND: Health-related quality of life (HRQoL) may be markedly impaired in patients with moderate-to-severe psoriasis. OBJECTIVES: Our objectives were to compare improvements in Dermatology Life Quality Index (DLQI) and Psoriasis Symptoms and Signs Diary (PSSD) scores between patients receiving guselkumab compared with placebo or adalimumab and to correlate these improvements with skin clearance. METHODS: Pooled phase III VOYAGE 1 and VOYAGE 2 data were evaluated through week 24. At baseline, patients were randomized to guselkumab 100 mg, placebo, or adalimumab 40 mg. At week 16, patients receiving placebo switched to guselkumab. Assessment measures included DLQI percent change from baseline, DLQI 0/1, DLQI minimal clinically important difference (MCID), individual domain scores, PSSD symptoms and signs score = 0, DLQI association with PSSD, Investigator's Global Assessment (IGA), and Psoriasis Area and Severity Index (PASI). RESULTS: Significantly greater improvements from baseline DLQI were observed with guselkumab versus placebo (weeks 8 and 16) and versus adalimumab (week 24; p < 0.001). The proportion of patients achieving DLQI 0/1 ("no impact") at week 24 was higher with guselkumab than with adalimumab (58.9 vs. 40.2%; p < 0.001), and more patients attained a ≥ 4-point reduction in DLQI (MCID) at this timepoint (p < 0.001). Changes in individual DLQI domains were significantly greater for patients receiving guselkumab than for those receiving adalimumab, and among patients with individual baseline domain scores = 3 or 6 (severest impact), more guselkumab recipients than those receiving adalimumab achieved a score = 0 across all domains at week 24. DLQI 0/1 scores were associated with a PSSD symptom or sign score = 0 (no impact) and greater improvement of PASI and IGA (week 24). CONCLUSIONS: Pooled VOYAGE 1/VOYAGE 2 data demonstrated that guselkumab was superior to adalimumab in improving HRQoL, which was associated with greater skin clearance. CLINICAL TRIAL REGISTRATION: NCT02207231 and NCT02207244.