Five-year maintenance of clinical response and health-related quality of life improvements in patients with moderate-to-severe psoriasis treated with guselkumab: results from VOYAGE 1 and VOYAGE 2.

BACKGROUND: Psoriasis is a chronic disease requiring long-term therapy. OBJECTIVES: Physician- and patient-reported outcomes were evaluated through week 252 in VOYAGE 1 and VOYAGE 2. METHODS: In total, 1829 patients were randomized at baseline to receive guselkumab 100 mg every 8 weeks, placebo or adalimumab. Patients receiving placebo crossed over to guselkumab at week 16. Patients receiving adalimumab crossed over to guselkumab at week 52 in VOYAGE 1, and randomized withdrawal and retreatment occurred at weeks 28-76 in VOYAGE 2; all patients then received open-label guselkumab through week 252. Efficacy and health-related quality of life (HRQoL) endpoints were analysed through week 252. Safety was monitored through week 264. RESULTS: The proportions of patients in the guselkumab group who achieved clinical responses at week 252 in VOYAGE 1 and VOYAGE 2, respectively, were 84·1% and 82·0% [≥ 90% improvement in Psoriasis Area and Severity Index (PASI)]; 82·4% and 85·0% [Investigator's Global Assessment (IGA) 0 or 1]; 52·7% and 53·0% (100% improvement in PASI) and 54·7% and 55·5% (IGA 0). HRQoL endpoints were achieved as follows: 72·7% and 71·1% of patients (Dermatology Life Quality Index 0 or 1: no effect on patient's life); 42·4% and 42·0% [Psoriasis Symptoms and Signs Diary (PSSD) symptom score = 0] and 33·0% and 31·0% (PSSD sign score = 0). As measured in VOYAGE 2 only, approximately 45% of patients achieved ≥ 5-point reduction in Short Form-36 physical and mental component scores, and 80% reported no anxiety or depression (Hospital Anxiety and Depression Scale scores < 8). Similar findings were reported for adalimumab crossovers. These effects were maintained from week 52 in VOYAGE 1 and week 100 in VOYAGE 2. No new safety signals were identified. CONCLUSIONS: Guselkumab maintains high levels of clinical response and improvement in patient-reported outcomes through 5 years in patients with moderate-to-severe psoriasis.

Utilization of the validated Psoriasis Epidemiology Screening Tool to identify signs and symptoms of psoriatic arthritis among those with psoriasis: a cross-sectional analysis from the US-based Corrona Psoriasis Registry.

BACKGROUND: Despite increasing awareness of the disease, rates of undiagnosed psoriatic arthritis (PsA) are high in patients with psoriasis (PsO). The validated Psoriasis Epidemiology Screening Tool (PEST) is a five-item questionnaire developed to help identify PsA at an early stage. OBJECTIVES: To assess the risk of possible undiagnosed PsA among patients with PsO and characterize patients based on PEST scores. METHODS: This study included all patients enrolled in the Corrona PsO Registry with data on all five PEST questions. Demographics, clinical characteristics and patient-reported outcomes were compared in Corrona PsO Registry patients with PEST scores ≥3 and <3 using t-tests for continuous variables and chi-squared tests for categorical variables; scores ≥3 may indicate PsA. RESULTS: Of 1516 patients with PsO, 904 did not have dermatologist-reported PsA; 112 of these 904 patients (12.4%) scored ≥3 and were significantly older, female, less likely to be working, and had higher BMI than patients with scores <3. They also had significantly longer PsO duration, were more likely to have nail PsO and had worse health status, pain, fatigue, Dermatology Life Quality Index and activity impairment. CONCLUSIONS: Improved PsA screening is needed in patients with PsO because the validated PEST identified over one-tenth of registry patients who were not noted to have PsA as having scores ≥3, who could have had undiagnosed PsA. Appropriate, earlier care is important because these patients were more likely to have nail PsO, worse health-related quality of life and worse activity impairment.

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.

Changes in C-reactive protein in patients with moderate-to-severe psoriasis switched to adalimumab therapy after suboptimal response to etanercept, methotrexate or phototherapy.

BACKGROUND: Psoriasis treatment can lower levels of the inflammatory biomarker C-reactive protein (CRP). OBJECTIVE: Evaluate CRP changes in patients with chronic plaque psoriasis who switched to adalimumab following suboptimal response to previous therapies. METHODS: C-reactive protein was measured at screening and after 16 weeks of adalimumab treatment following discontinuation of previous therapies: etanercept (substudy E; n = 77), methotrexate (substudy M; n = 38) or narrow-band ultraviolet B phototherapy (substudy P; n = 27). Associations of CRP with baseline characteristics and efficacy measures were evaluated. RESULTS: Median CRP change at the final visit was -0.3 mg/L overall and -0.4, -0.3 and -0.3 mg/L in substudies E, M and P respectively. Clinical response [Physician Global Assessment (PGA) 'clear' or 'minimal'] was associated with greater CRP reductions vs. no response (PGA 'mild' or worse) overall (-0.4 vs. -0.3 mg/L) and in substudies E (-0.4 vs. -0.1 mg/L) and M (-0.5 vs. -0.2 mg/L), but not P (-0.1 vs. -0.4 mg/L). CRP decreases were, respectively, -0.4 and -0.3 mg/L in patients with and without a history of psoriatic arthritis and -0.1, -0.3 and -0.6 mg/L in normal weight, overweight and obese patients, respectively. CRP decreases after 16 weeks correlated positively (ß = 0.004) with percentage change in Psoriasis Area and Severity Index (PASI; P = 0.0398) and negatively (ß = -0.360) with baseline CRP (P < 0.0001). CONCLUSION: C-reactive protein levels decreased during adalimumab therapy in patients with psoriasis who experienced suboptimal response to previous therapies. Clinical response was associated with greater CRP reductions overall and in substudies E and M, but not P. CRP reductions correlated with percentage reductions in PASI.

Inflammatory arthritis following ustekinumab treatment for psoriasis: a report of two cases.

Psoriasis is a chronic inflammatory skin condition, characterized by T-helper (Th) 1 and Th17 cell activation. Ustekinumab is a fully human immunoglobulin G1κ monoclonal antibody that targets the common p40 subunit that is shared by both interleukin (IL)-12 and IL-23, consequently inhibiting T-cell differentiation along both Th1 and Th17 pathways. This is a report of two patients who developed psoriatic arthritis during ustekinumab treatment for psoriasis. Neither patient had a personal or family history of arthritis.

Sleep quality and other patient-reported outcomes improve after patients with psoriasis with suboptimal response to other systemic therapies are switched to adalimumab: results from PROGRESS, an open-label Phase IIIB trial.

BACKGROUND: Psoriasis is associated with poor health-related quality of life, including sleep impairment. OBJECTIVE: To assess the extent of sleep impairment, the effect of adalimumab on sleep and other patient-reported outcomes, and correlations between changes in these outcomes and sleep quality in patients with psoriasis. METHODS: Patients in the 16-week, open-label, Phase IIIb PROGRESS trial had chronic plaque psoriasis and suboptimal response to prior therapy (etanercept, methotrexate or narrowband ultraviolet B phototherapy). Adalimumab was self-injected subcutaneously (80 mg at week 0, then 40 mg every other week from week 1). The focus for this analysis was the Medical Outcomes Study Sleep Scale. Other patient-reported outcomes included the Dermatology Life Quality Index (DLQI), Psoriasis Area and Severity Index (PASI), Physician's Global Assessment, a visual analogue scale for psoriasis/psoriatic arthritis (PsA) pain, and the Work Productivity and Activity Index Questionnaire-Specific Health Problems. RESULTS: Patients with psoriasis had impaired sleep at baseline. The degree of sleep impairment was significantly associated with the extent of work productivity for all sleep measures and, for some sleep measures, was associated with DLQI impairment, clinical severity measured by PASI, the presence of PsA, and depression. Adalimumab treatment significantly improved sleep quality by 15% from baseline, as well as DLQI score, pain and work productivity. The improvement in sleep was partially explained (R(2 ) = 0·16, P < 0·001) by improvements in the objectively measured psoriasis signs in PASI. CONCLUSIONS: Adalimumab treatment improved sleep outcomes and other patient-reported outcomes including health-related quality of life, work productivity, daily activity and disease-related pain.

A randomized, double-blind, placebo-controlled study to evaluate the addition of methotrexate to etanercept in patients with moderate to severe plaque psoriasis.

BACKGROUND: Etanercept plus methotrexate combination therapy has not been adequately investigated in psoriasis. OBJECTIVES: To evaluate etanercept plus methotrexate vs. etanercept monotherapy in patients with moderate to severe plaque psoriasis who had not failed prior methotrexate or tumour necrosis factor-inhibitor therapy. METHODS: Patients received etanercept 50 mg twice weekly for 12 weeks followed by 50 mg once weekly for 12 weeks and were randomized 1 : 1 to receive methotrexate (7·5-15 mg weekly) or placebo. The primary endpoint was the proportion of patients achieving ≥75% improvement in Psoriasis Area and Severity Index (PASI 75) at week 24. RESULTS: In total, 239 patients were enrolled in each arm. PASI 75 was significantly higher at week 24 for the combination therapy group compared with the monotherapy group (77·3% vs. 60·3%; P < 0·0001). Other PASI improvement scores at week 12 [PASI 75, 70·2% vs. 54·3% (P = 0·01); PASI 50, 92·4% vs. 83·8% (P = 0·01); and PASI 90, 34·0% vs. 23·1% (P = 0·03)] showed similar results as did week 24 PASI 50 (91·6% vs. 84·6%; P = 0·01) and PASI 90 (53·8% vs. 34·2%; P = 0·01). Significantly more patients receiving combination therapy than monotherapy had static Physician's Global Assessment of clear/almost clear at week 12 (65·5% vs. 47·0%; P = 0·01) and week 24 (71·8% vs. 54·3%; P = 0·01). Adverse events (AEs) were reported in 74·9% and 59·8% of combination therapy and monotherapy groups, respectively; three serious AEs were reported in each arm. CONCLUSIONS: Combination therapy with etanercept plus methotrexate had acceptable tolerability and increased efficacy compared with etanercept monotherapy in patients with moderate to severe psoriasis.

Efficacy and safety results from a phase III, randomized controlled trial comparing the safety and efficacy of briakinumab with etanercept and placebo in patients with moderate to severe chronic plaque psoriasis.

BACKGROUND: The tumour necrosis factor-α antagonist etanercept and the interleukin (IL)-12/23p40 antagonist ustekinumab have been shown to be effective psoriasis therapies. The IL-12/23p40 antagonist briakinumab was shown to be effective psoriasis treatment in a phase II study. OBJECTIVES: To assess the efficacy, safety and tolerability of briakinumab compared with etanercept and placebo in patients with moderate to severe psoriasis. METHODS: Three hundred and fifty patients were enrolled in this phase III, 12-week study (M10-315, NCT00710580) and randomized in the following 2:2:1 ratio: 139 patients received 200 mg briakinumab at weeks 0 and 4 followed by 100 mg briakinumab at week 8; 139 patients received 50 mg of etanercept twice weekly 3-4 days apart at weeks 0-11; 72 patients received placebo injections matching active treatment. The co-primary efficacy endpoints were the proportion of patients achieving a Physician's Global Assessment (PGA) of 0/1 at week 12, and the proportion of patients achieving a Psoriasis Area and Severity Index (PASI) 75 response at week 12. RESULTS: Of the briakinumab-treated patients, 72·7% achieved a PGA of 0/1 at week 12 as compared with 29·5% of etanercept-treated patients and 4·2% of placebo-treated patients (P < 0·001, for both comparisons). Of the briakinumab-treated patients, 80·6% achieved a PASI 75 response at week 12 as compared with 39·6% of etanercept-treated and 6·9% of placebo-treated patients (P < 0·001, for both comparisons). Serious adverse events were reported in two (1·4%) briakinumab-treated patients, one (0·7%) etanercept-treated patient and two (2·8%) placebo-treated patients. CONCLUSIONS: In patients with moderate to severe psoriasis, briakinumab had superior efficacy to both placebo and etanercept at 12 weeks as administered in this study.

Benefit-risk assessment of tumour necrosis factor antagonists in the treatment of psoriasis.

BACKGROUND: Safety of tumour necrosis factor (TNF) antagonists is a primary concern for clinicians prescribing them to patients with psoriasis. OBJECTIVES: To determine the benefit-risk balance of TNF antagonists in psoriasis. METHODS: Through integrated analyses of published literature, we calculated the number needed to treat (NNT) for various efficacy measures and the number needed to harm (NNH) for various adverse events for approved dosing regimens of adalimumab, etanercept and infliximab. Integrated analyses that included open-label safety data from TNF-antagonist clinical trials were also conducted. RESULTS: PASI 75 treatment effect data from the literature result in NNT values of 1·6 (95% confidence interval, CI 1·5-1·7) for adalimumab 40 mg every other week; 3·2 (95% CI 2·8-3·7) for etanercept 50 mg weekly or 25 mg twice weekly, and 2·3 (95% CI 2·1-2·5) for etanercept 50 mg twice weekly; and 1·4 (95% CI 1·3-1·5) for infliximab 5 mg kg(-1) dosing. For serious noninfectious, serious infectious and malignant adverse events, point estimates of the NNHs are generally at least two orders of magnitude larger than the NNTs, and the 95% CIs for the NNHs for adalimumab, etanercept and infliximab overlap. Analyses that included open-label data corroborated, with increased exposure to study agents, the low risk of adverse events observed in placebo-controlled periods. CONCLUSIONS: These analyses demonstrated that, during the initial year of treatment, the likelihood of success with anti-TNF therapy for psoriasis was several orders of magnitude greater than the likelihood of serious toxicity.

Obesity in psoriasis: the metabolic, clinical and therapeutic implications. Report of an interdisciplinary conference and review.

Experts on psoriasis convened with authorities from other medical specialties to discuss the recently described association between psoriasis, obesity and subsequent cardiovascular comorbidity. Similar to other diseases of increased systemic inflammation, psoriasis has been linked to a heightened risk of myocardial infarction, especially in the more severely affected, younger patients. However, unlike in other inflammatory diseases - such as rheumatoid arthritis - more severely affected patients with psoriasis are much more likely to be obese. Importantly, the pathophysiology of both psoriasis and obesity shows many shared cytokines that are known to contribute to features of the metabolic syndrome, such as hypertension, dyslipidaemia and insulin resistance. The strong association between psoriasis and obesity potentially makes psoriasis an important healthcare issue that requires an update in its standard of care. This meeting reviewed the evidence-based literature and addressed how, moving forward, dermatologists and other specialists may redefine the magnitude of health risk associated with more severe psoriasis and its comorbidities, while clarifying both the epidemiology and pathophysiology of the association with obesity.

Comparison of clinical and pharmacokinetic profiles of etanercept 25 mg twice weekly and 50 mg once weekly in patients with psoriasis.

BACKGROUND: Etanercept is a tumour necrosis factor antagonist that is approved in the U.S.A., Canada and Europe for treating adult patients with chronic moderate to severe plaque psoriasis. OBJECTIVES: To assess whether clinical efficacy, safety and pharmacokinetic (PK) profiles of etanercept 50 mg once weekly are comparable to etanercept 25 mg twice weekly. METHODS: Patients from a U.S. phase 3 study and a global phase 3 study were subsequently enrolled in an open-label extension study (extension study) where they all received etanercept at a dose of 50 mg once weekly for an initial 12 weeks. Patients who had received at least 24 weeks of etanercept 25 mg twice weekly in the global phase 3 study and were enrolled in the extension study (n = 265) were assessed for efficacy and safety at extension study baseline and after 12 weeks of etanercept 50 mg once weekly. Efficacy endpoints included the Psoriasis Area and Severity Index (PASI), the Dermatology Life Quality Index and the Physician's Global Assessment of psoriasis. In addition, PK profiles from patients in the U.S. phase 3 study were compared with PK profiles from another set of patients in the extension study. Comparison was made between a subset of patients receiving etanercept 25 mg twice weekly dosing in the U.S. phase 3 study (n = 13) and those receiving etanercept 50 mg once weekly in the extension study (n = 84). RESULTS: The mean PASI score was 5.77 at extension study baseline after treatment with etanercept 25 mg twice weekly, which was sustained at 5.82 after 12 weeks of etanercept 50 mg once weekly. Similar results were observed in other efficacy endpoints. Etanercept 50 mg once weekly was generally well tolerated. No new safety findings were reported. PK profiles overlapped extensively between the two dosing regimens. CONCLUSIONS: In this report, we demonstrate that efficacy, safety and PK profiles were comparable between etanercept 25 mg twice weekly and 50 mg once weekly in patients who had received at least 24 weeks of etanercept 25 mg twice weekly prior to receiving etanercept 50 mg once weekly in the extension study.

Toxic epidermal necrolysis-like reaction secondary to colchicine overdose.

Colchicine is a microtubule-inhibiting drug used to treat gout, familial Mediterranean fever and many other skin diseases. Intoxication with colchicine affects multiple organs, often fatally. Cutaneous sequelae of colchicine toxicity are rare. We describe the clinical and histological features of a toxic epidermal necrolysis-like exanthem in a patient who lethally overdosed on colchicine.

Eyelash hypertrichosis in a patient treated with topical latanoprost.

We describe a female patient with a history of primary open-angle glaucoma who, following treatment with topical latanoprost, a synthetic prostaglandin F2 alpha analog, developed hypertrichosis of the eyelashes. Hypertrichosis, a recently described side effect of latanoprost--together with iridal pigmentation--represents a potentially permanent cosmetic side effect associated with the use of this highly effective intraocular pressure-lowering agent. The molecular mechanism underlying latanoprost-induced hypertrichosis is unknown.