As part of the National Institute for Health and Care Excellence single technology appraisal process, brodalumab was assessed to determine the clinical and cost effectiveness of its use in the treatment of moderate-to-severe plaque psoriasis. The Centre for Reviews and Dissemination and the Centre for Health Economics Technology Assessment Group at the University of York were commissioned to act as the independent Evidence Review Group. This article provides a summary of the Evidence Review Group's review of the company's submission, the Evidence Review Group report and the National Institute for Health and Care Excellence Appraisal Committee's subsequent guidance issued in March 2018. The main clinical effectiveness data were derived from three well-conducted, multicentre, double-blind randomised controlled trials. The trials demonstrated that brodalumab statistically significantly reduced the severity of psoriasis and its impact on health-related quality of life, compared with placebo, at 12 weeks. In comparison with ustekinumab, statistically significantly more patients taking brodalumab had reduced psoriasis severity at 12 weeks. Psoriasis severity and quality of life also appeared improved at 52 weeks, although statistical significance was not assessed. Withdrawal rates were comparable to drug survival rates of other biological therapies and rates of adverse events were similar between brodalumab and ustekinumab. A network meta-analysis was presented, comparing brodalumab with other therapies available at the same point in the treatment pathway (i.e. in patients for whom standard systemic therapy or phototherapy is inadequately effective, not tolerated or contraindicated). The network meta-analysis ranked treatments in order of effectiveness, in terms of achieving different levels of Psoriasis Area and Severity Index response. The results indicated that brodalumab had a similar probability of response to ixekizumab, secukinumab and infliximab and a higher probability of response than ustekinumab, adalimumab, etanercept, apremilast, dimethyl fumarate and placebo. The company's economic model compared nine treatment sequences that included three lines of active therapy, consisting of brodalumab and other comparators recommended by the National Institute for Health and Care Excellence, followed by best supportive care. The sequence with brodalumab in the first-line position dominated sequences that started with adalimumab, infliximab, secukinumab and ustekinumab. The incremental cost-effectiveness ratio of the brodalumab sequence compared to less effective and non-dominated sequences ranged from £7145 (vs. the etanercept sequence) to £13,353 (vs. the dimethyl fumarate sequence) per quality-adjusted life-year gained. The incremental cost-effectiveness ratio for the more costly and effective ixekizumab sequence was £894,010 per quality-adjusted life-year gained compared to the brodalumab sequence. At a threshold of £20,000 per quality-adjusted life-year gained, the brodalumab sequence had the highest probability of being cost effective (96%). The main limitation of the company's economic model was the restrictive nature of the sequences compared. Twelve separate scenarios based on key uncertainties were explored by the Evidence Review Group. The only scenarios where brodalumab was ranked lower than first were not considered to be more appropriate or plausible than the assumptions or scenarios included in the company's base case. The treatment rankings identified in the Evidence Review Group's alternative base case were identical to those derived from the company's base case model. At the first National Institute for Health and Care Excellence Appraisal Committee meeting, the Committee concluded that brodalumab appears to be as effective as other anti-interleukin-17 agents and is cost effective, based on the discount agreed in the patient access scheme. Brodalumab is recommended as an option for treating adults with severe plaque psoriasis (defined by a total Psoriasis Area and Severity Index score of 10 or more and a Dermatology Life Quality Index score of more than 10) who have not responded to other systemic non-biological therapies. Brodalumab should be stopped at 12 weeks if the psoriasis has not responded adequately.

Determine disease activity in a low income juvenile idiopathic arthritis (JIA) cohort. 164 JIA patients from families with less than US$ 4500.00/capita mean annual income followed in Fortaleza-CE, Brazil, were cross-sectionally evaluated between May 2015-April 2016. Mean age was 14 ± 5.1 years (95 female) with 10.31 ± 3.7 years disease duration. Polyarticular category predominated, with 63 (38.4%) patients, followed by 40 (24%) enthesitis-related (ERA), and 36 (22%) oligoarticular. All but 1 out of 84 parents declared less than US$ 10,000.00 annual family income. Eighty-eight (60.7%) were receiving methotrexate and 19 (13%) leflunomide including 12 (63%) using both; 46 (28%) were on biologic DMARD including 20 (43.5%) adalimumab, 17 (41.5) etanercept, 5 (10.8%) tocilizumab, 2 (4.2%) abatacept, and 1 (2.1%) each on infliximab and canakinumab. Mean CHAQ and JADAS27 were 0.36 ± 0.55 and 5.31 ± 8.5, respectively. Thirty-two (20%) out of 159 patients had deformities. A bivariate analysis revealed that polyarticular had more deformities than oligoarticular patients (p = 0.002; OR = 2.389; 95% CI 1.37-4.14). Logistic regression showed no association between high JADAS and family income (p = 0.339; OR = 1.45; 95% CI 0.67-3.31). A general linear model showed significantly lower CHAQ score in patients from families earning more as compared to those earning less than 300.00 US$ monthly (p = 0.002). This study reports JIA disease activity in a low income population. Low income apparently did not influence prognosis given the low mean JADAS27 and CHAQ scores vis-à-vis data from other cohorts.

To compare the efficacy of adalimumab (ADA) and infliximab (IFX) in patients with non-infectious intermediate uveitis, posterior uveitis, and panuveitis. Demographic, clinical, instrumental, and therapeutic data from patients enrolled were collected at the start of treatment, at 12-month follow-up, and at the last follow-up assessment. One hundred seven patients (46 females, 187 eyes) were enrolled, 66 (61.7%) treated with ADA and 41 (38.3%) with IFX. Bilateral involvement was observed in 80 cases. The mean follow-up was 26.45 ± 21.71 months for ADA patients and 56.60 ± 56.04 months for IFX patients. The overall decrease of uveitis frequency during the first 12 months of treatment was 66.7% in the IFX group and 84.2% in the ADA group, compared to the previous 12 months (p = 0.09). A significantly higher corticosteroid dosage was found among patients treated with ADA at the last follow-up visit (p = 0.008). The percentage of patients co-administered with corticosteroids was significantly higher among ADA patients both at the 12-month visit (p = 0.03) and at the last visit (p = 0.0004). The frequency of uveitic macular edema (UME) was significantly higher among patients treated with ADA compared to those treated with IFX at the 12-month assessment (p = 0.015) and at the last follow-up visit (p = 0.011); central macular thickness was significantly higher in ADA group compared to the IFX group at the last follow-up assessment (p = 0.04). ADA and IFX have shown a similar efficacy in controlling uveitis relapses, but IFX showed a more pronounced corticosteroid sparing effect and a significantly higher capacity in resolving UME compared to ADA.

Adalimumab is one of the top-selling drugs worldwide. Its imminent patent expiration has seen the emergence of numerous biosimilar agents. In this article, we recap the evidence from bio-originator trials in rheumatoid arthritis (RA) to provide context for a critical review of biosimilar trial data.