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Take a look at a selection of our recent media coverage:
7th September 2021
The National Institute for Health and Care Excellence (NICE) has approved the use of the monoclonal antibody Cosentyx (secukinumab) as an option for the treatment of plaque psoriasis in children and young people aged 6 to 17 years of age. It is only recommended where the psoriasis area and severity index (PASI), which is a measure of disease severity, is greater than 10 (meaning moderate to severe disease) and where other systemic therapies have been unsuccessful. The systemic therapies mentioned in the guidance are ciclosporin, methotrexate, as well as phototherapy, although Cosentyx can also be used in cases where any of these treatments are contra-indicated. In addition, NICE has recommended use of Cosentyx only where the manufacturer provides the drug in line with an agreed commercial arrangement.
The outcome of interest when using Cosentyx is the achievement of a PASI75, i.e., a 75% improvement in disease severity, after 12 weeks of treatment. If such an improvement has not occurred, then NICE recommends stopping Cosentyx. A further point in the guideline is that where a clinician considers that secukinumab is the most appropriate therapy, the least expensive option should be used and it has been increasing recognised that there are huge potential and achievable savings for the NHS through the use of biosimilars,
In making its decision, NICE received information on the comparative clinical efficacy of other biologics used in psoriasis including etanercept, adalimumab and ustekinumab. The committee noted from studies that secukinumab was more effective than etanercept, based on a higher proportion of participants achieving a PASI75 and that the efficacy was comparable with ustekinumab. Although there were no direct comparisons of Cosentyx with adalimumab in the paediatric population, a network meta-analysis submitted by the manufacturer, showed that adalimumab was as effective as ustekinumab. Furthermore, there were no differences in safety outcomes for Cosentyx compared with other similar biologics.
Source. NICE 2021
24th August 2021
Psoriasis is best described as a complex, chronic, multifactorial and inflammatory disease characterised by increased proliferation of keratinocyte cells in the skin giving rise to silvery/white plaques. The disease typically presents on extensor surfaces such as the elbows, knees and lower back and there if often involvement of the scalp. The incidence of psoriasis appears to vary across the world, with a recent study noting a wide variation. For instance, the incidence was 30.3 per 100,000 person years in Taiwan but 321 per 100,000 person years in Italy. Among those with psoriasis, one study of over 9,000 patients, found that just over half (51.8%) had mild disease, with 35.8% and 12.4% having moderate and severe disease respectively. Patients with mild to moderate disease are normally managed with topical therapies, whereas those with moderate to severe disease are increasing treated with biological agents, in particular, monoclonal antibodies. Although the precise cause of psoriasis remains to be determined, several interleukins appear to be important disease drivers, especially the interleukin-17 (IL-17) pathway which includes six similar agents, IL-17A – IL-17F. Research suggests that two members of the IL-17 family, IL-17A and IL-17F are implicated in autoimmunity and IL17F appears to regulate pro-inflammatory gene expression and which requires the IL-17A receptor, suggesting that both are involved in the pathology of psoriasis. Bimekizumab is the first monoclonal antibody which selectively inhibits both IL-17A and IL-17F and is therefore a potentially important advancement in the management of patients with moderate to severe psoriasis.
The EU approval of bimekizumab was supported by the results of three phase 3 clinical trials, all undertaken in patients with moderate to severe psoriasis. The first, BE READY, randomised 435 patients (4:1) to bimekizumab 320 mg every 4 weeks or placebo. The co-primary endpoint was a PASI90 (i.e., 90% improvement in disease severity compared to baseline) and the proportion of patients achieving a score of 0 (i.e., clear skin) or 1 (almost clear), based on a 5-point investigator global assessment (IGA) score after 16 weeks of treatment. The results showed that a staggering 91% of those assigned to bimekizumab achieved a PASI90 compared to only 1% in the placebo group. In the BE VIVID trial, 567 patients were randomised to bimekizumab (at the same dosage as the BE READY trial) or this time, ustekinumab 45 or 90 mg every 12 weeks and which is an active comparator or placebo. Once again at week 16 there was a high response in the bimekizumab group with 85% achieving a PASI90 compared to 50% in the ustekinumab. The third trial, BE SURE, enrolled 478 patients who were randomised to either bimekizumab (same dosage as in the other trials) or adalimumab (another active comparator) at a dose of 40 mg every 2 weeks. At week 16, a PASI90 was achieved 85.3% of those using bimekizumab and 57.2% of those given adalimumab.
The most common adverse effects from bimekizumab are upper respiratory tract infections (14.5%) and patients are advised to seek medical advice if they display symptoms suggestive of an infection.
The EU approval applies to all 27 member states as well as Iceland, Liechtenstein and Norway at a dose of 320 mg administered by subcutaneous injections every 4 weeks for week 16 and every 8 weeks thereafter. The drug is currently under review by the US Food and Drug administration.
Source: UCB press release 2021
11th June 2021
Psoriasis is a chronic, inflammatory conditions that affects 1% of children and adolescents in the US. Moreover, due to the visible nature of the condition, psoriasis can have a negative impact on children’s quality of life.
The interleukin-17A (IL-17A) inhibitor, secukinumab (brand name Cosentyx) can now be used for the treatment of moderate-to-severe psoriasis in children from the age of six who are candidates for systemic or phototherapy because of the severity of their psoriasis. The drug has more than 14 years of clinical experience and long-term, 5-year clinical data. The approved dosing is 75 or 150mg, depending on the child’s weight (i.e., 75mg for those < 50kg and 150mg > 50kg) and the drug is administered by subcutaneous injection every four weeks after an initial loading regime. A further advantage is that after suitable counselling, the dose can be given by an adult carer, hence avoiding the need to visit a healthcare professional.
The approval of Cosentyx was based on the results of two Phase III trials that were undertaken in children aged between 6 and 18 years. The first trial was a 52-week, randomised, double-blind, placebo controlled study with 162 children with severe plaque psoriasis. The study had a co-primary endpoint: the proportion achieving a psoriasis area severity index (PASI) 75 score (i.e., a 75% improvement in disease severity) and an investigator’s global assessment of either “clear” (no psoriasis) or “almost clear” at week 12.
Among children <50kg, after 12 weeks, 55% vs 10% (Cosentyx vs placebo) had achieved a PASI 75. Similarly in those weighing >50kg, the corresponding PASI 75 values were 86% vs 19% (Cosentyx vs placebo). For children weighing <50kg, the proportion achieving a score of clear or almost clear was 32% vs 5% (Cosentyx vs placebo). Similarly, among children weighing > 50kg, the corresponding values were 81% vs 5%.
The second trial was designed to assess safety although the press release contains no data from this study and at present, neither study has been published.
Discussing the new approval, Randy Beranek, President and CEO of the National Psoriasis Foundation, said “Having expanded treatment options for this patient population is a step in the right direction to help reduce the burden of plaque psoriasis“.
7th December 2020
Real-world data can be derived from patient registries and are of value because they illustrate whether the expected efficacy determined in a randomised trial holds up in practice. Using information held in the British Association of Dermatologists Biologics and Immunomodulators Register (BADBIR), a team from the Centre for Dermatology, Salford, UK, examined the comparative effectiveness of two biologics, secukinumab and ustekinumab used in patients with moderate to severe psoriasis, defined in terms of a psoriasis and area severity index (PASI) of 12 or more prior to starting with either biologic. The PASI serves as a measure of disease severity with scores above 10, indicating at least moderate disease severity. The researchers restricted the drug initiation dates to on or after September 2013 (when both drugs became available) and before September 2018, to allow for patients to have completed at least 12 months of therapy. The primary outcome for the study was the difference in the proportion of patients who achieved a PASI of 2 or lower (i.e. virtually disease free) after 12 months of therapy. The authors used the results of a recent RCT in which the two biologics were studied head-to-head, as a baseline to compare the effectiveness data derived from the BADBIR registry.
A total of 1231 patients were included, 917 receiving ustekinumab (mean age 45 years, 40% female) and the remainder secukinumab (mean age 46 with 38% female). A PASI at 12 months post-treatment was available for only 42% and 45.5% of those given secukinumab and ustekinumab respectively. Secukinumab was superior to ustekinumab in achieving a PASI of 2 (relative risk = 1.28, 95% CI 1.06 – 1.55). However, a further and important finding from the BADBIR registry data was that the estimate of efficacy from the RCT appeared much lower in practice. For example, secukinumab and ustekinumab were 17.5% and 15.1% less effective than the RCT data would suggest.
Commenting on these findings, the authors suggested that given this discrepancy, clinicians should aim to inform patients prescribed either drug that the true effectiveness was likely to be lower than expected based on the results shown in the clinical trial.
You ZZN et al. Randomised trial replication using observational data for comparative effectiveness of secukinumab and ustekinumab in psoriasis. A study from the British Association of Dermatologists Biologics and Immunomodulators register. JAMA Dermatol 2020