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Altres ajuts: The AMAGINE-1, AMAGINE-2 and AMAGINE- 3 trials were sponsored by Amgen and AstraZeneca; this analysis was performed by LEO Pharma. Medical writing support was provided by Ian Eustace from Adelphi Communications Ltd, Bollington, UK, funded by LEO Pharma. Background: Modern biologics achieve complete skin clearance [100% improvement in psoriasis area and severity index (PASI 100)] in 30-45% of psoriasis patients. Cumulative benefit considering rapidity, frequency and sustainability of response has not been thoroughly investigated. Objectives: Compare the frequency, rapidity and sustainability of PASI 90 and 100 response in patients with moderate-to-severe psoriasis treated with brodalumab or ustekinumab. Methods: Integrated analyses of the brodalumab Phase III AMAGINE-2 (NCT01708603) and -3 (NCT01708629) trials were performed to determine proportion of patients achieving PASI response per visit; corresponding odds ratios (OR) were calculated. Cumulative clinical benefit of treatment was determined with area-under-the-curve (AUC) analysis. Cumulative incidence of response was analysed using a competing risk model of PASI response or rescue. Sustained response was evaluated by time to inadequate response using Kaplan-Meier methods. Proportion of time spent in different response states was descriptively analysed. Association between PASI response and health-related quality of life [Dermatology Life Quality Index (DLQI)] was assessed using data from all treatment groups from AMAGINE-1, -2 and -3. Results: A significantly higher proportion of patients treated with brodalumab achieved PASI 100 vs. ustekinumab (Week 52: 51% vs. 28%; OR [95% CI] 2.8 [2.1, 3.7]; P < 0.0001), with significant differences observed from Week 4. Cumulative benefit through 52 weeks was 69% higher with brodalumab (AUC ratio: 1.69; P < 0.001). Brodalumab patients were also significantly more likely to achieve a PASI 100 at least once over 52 weeks vs. ustekinumab (76% vs. 52%; P < 0.0001). Once response was achieved, brodalumab patients had a low likelihood of failure or need for rescue. There was significant positive association between PASI response level and DLQI0/1 achievement (P < 0.0001). Conclusion: Brodalumab treatment resulted in significantly higher levels of skin clearance, longer sustained response and greater cumulative treatment benefit vs. ustekinumab.

Altres ajuts: Amgen; AstraZeneca. Background: The pathway for treatment of psoriasis is partly dependent upon disease severity, and patients may experience inadequate response at any point along the treatment pathway. Patients who repeatedly fail therapy represent a population in whom effective and well-tolerated treatment options are limited. Objectives: To investigate and describe patients achieving Psoriasis Area and Severity Index (PASI) 100 and cumulative treatment benefit over time in patients with moderate-to-severe psoriasis receiving brodalumab or ustekinumab by prior treatment. Methods: We conducted a post hoc analysis of data from two phase 3, randomized, controlled, 52-week AMAGINE trials of brodalumab to describe patients who achieved complete clearance as measured by PASI 100 by prior treatment subgroup (naïve to systemic and biologic treatment, systemic-treated but biologic-naïve, biologic-treated without failure, and biologic-treated with failure). A competing risk model was used to assess cumulative incidence over a 52-week period with outcomes of PASI 100 or inadequate response. Cumulative clinical benefit of treatment was determined with an area under the curve analysis. Results: The 52-week cumulative incidence of patients achieving PASI 100 was consistently higher for brodalumab vs. ustekinumab across treatment pathway subgroups (76% vs. 58% in systemic/biologic-naïve patients, 78% vs. 55% in systemic-treated/biologic-naïve patients, 75% vs. 41% in biologic-treated patients without failure, and 70% vs. 30% in biologic-treated patients with failure). Rates of inadequate response were lower with brodalumab compared with ustekinumab across all subgroups. Cumulative treatment benefit was also higher for all subgroups treated with brodalumab compared with those treated with ustekinumab. Conclusion: Treatment with brodalumab was associated with higher levels of complete clearance and greater cumulative benefit over time compared with ustekinumab, in patients with moderate-to-severe psoriasis, regardless of prior treatment experience.

BACKGROUND: Patients with plaque psoriasis treated with biologic therapies need more efficacious, safe, and convenient treatments to improve quality of life. Risankizumab and secukinumab inhibit interleukin (IL)-23 and IL-17A, respectively, and are effective in adult patients with moderate-to-severe plaque psoriasis but have different dosing regimens.OBJECTIVES: Directly compare efficacy and safety of risankizumab vs. secukinumab over 52 weeks.METHODS: IMMerge was an international, phase 3, multicentre, open-label, efficacy assessor-blinded, active-comparator study, in which adult patients with chronic, moderate-to-severe plaque psoriasis were randomised in a 1:1 ratio to treatment with risankizumab 150mg or secukinumab 300mg. Primary efficacy end points were proportions of patients achieving ≥90% improvement from baseline in Psoriasis Area Severity Index (PASI 90) at week 16 (noninferiority comparison with margin of 12%) and week 52 (superiority comparison).RESULTS: A total of 327 patients from nine countries were treated with risankizumab (n=164) or secukinumab (n=163). Risankizumab was noninferior to secukinumab in proportion of patients achieving PASI 90 at week 16 [73∙8% vs. 65∙6%; difference of 8∙2% [96∙25% confidence interval (CI) -2∙2, 18∙6] within 12% noninferiority margin], and superior to secukinumab at week 52 [86∙6% vs. 57∙1%; difference of 29∙8% (95% CI 20∙8, 38∙8); PCONCLUSIONS: At week 52, risankizumab demonstrated superior efficacy and similar safety with less frequent dosing compared with secukinumab.

BACKGROUND: Tildrakizumab is a specific anti-interleukin-23p19 monoclonal antibody approved for the treatment of plaque psoriasis.OBJECTIVES: To evaluate the long-term efficacy and safety of tildrakizumab treatment for patients with moderate-to-severe psoriasis for up to 148 weeks.METHODS: Pooled analysis from two double-blind, randomized controlled trials: reSURFACE 1 and reSURFACE 2. Efficacy was assessed for responders (≥ 75% improvement in Psoriasis Area and Severity Index; PASI 75) and partial responders (PASI 50-75) to tildrakizumab 100 mg and 200 mg at week 28 who were maintained on the same dose (administered every 12 weeks), and for partial responders or nonresponders (PASI < 50) to etanercept 50 mg at week 28 who, after a 4-week washout, were switched to tildrakizumab 200 mg (administered at weeks 32 and 36, and every 12 weeks thereafter). Safety was assessed in the all-patients-as-treated population. Three different methods of imputing missing data were used: nonresponder imputation (NRI), multiple imputation and observed cases. The Clinicaltrials.gov numbers are NCT01722331 (reSURFACE 1) and NCT01729754 (reSURFACE 2).RESULTS: At week 148 (NRI), 72·6%, 53·8% and 28·9% of tildrakizumab 100-mg responders and 80·2%, 59·9% and 32·6% of tildrakizumab 200-mg responders had PASI 75, 90 and 100 responses, respectively. For partial responders to tildrakizumab 100 mg and 200 mg, the proportions of patients achieving PASI 75, 90 and 100 responses were 32·5%, 25·0% and 10·0%; and 47·1%, 27·5% and 12·8%, respectively. For patients who were partial responders or nonresponders to etanercept, the proportions of patients achieving PASI 75, 90 and 100 responses were 66·9%, 43·8% and 14·9% at week 148. Rates of discontinuations due to adverse events [tildrakizumab 100 mg: 1·7 per 100 patient-years (PYs); tildrakizumab 200 mg: 1·2 per 100 PYs] and exposure-adjusted rates of serious adverse events (5·9 per 100 PYs; 5·5 per 100 PYs), severe infections (1·1 per 100 PYs; 1·1 per 100 PYs), malignancies (0·6 per 100 PYs; 0·4 per 100 PYs) and major adverse cardiovascular events (0·4 per 100 PYs; 0·5 per 100 PYs) were low.CONCLUSIONS: Tildrakizumab was well tolerated and efficacy was well maintained in week 28 responders who continued tildrakizumab treatment through 3 years, or improved among etanercept partial responders or nonresponders who switched to tildrakizumab.