This Franco-Belgian multicentre study provides valuable real-world data on the effectiveness and safety of brodalumab in the treatment of moderate-to-severe psoriasis in adults. At W12/16, nearly half of the patients achieved complete clearance of their psoriasis, and this effectiveness was sustained at W52, with 62% of patients remaining completely cleared. This outcome demonstrates the effectiveness of brodalumab over time, which is consistent with findings from previous clinical trials [4] as well as real-world studies [22,23,24,25,26,27,28,29]. These results further emphasize brodalumab’s potential as a relevant therapeutic option for patients with moderate-to-severe psoriasis.

In addition to PASI scores, the improvement in quality of life, as measured by the DLQI questionnaire, also underscores the benefit of brodalumab treatment. Improvements in the mean DLQI, as well as the proportion of patients achieving DLQI ≤ 1 and DLQI decrease ≥ 4 points (DLQId4), were observed at both W12/16 and W52. Nevertheless, quality of life is influenced by seasonality, especially for the patients with chronic diseases. Seasonality significantly affects mental health and can be seen even in laboratory animals [30]. Analysis of DLQI at 12/16 weeks could be impacted by seasonality, while taking into account DLQI over a period of 52 weeks reduces the impact of seasonality. DLQI improvements reflect the clinical relevance of brodalumab, as the reduction in quality-of-life burden is a critical consideration for patients with psoriasis. Moreover, the consistency of these results over time further supports the role of brodalumab in improving both the clinical and functional aspects of psoriasis management.

From a safety perspective, 26.6% of patients experienced AEs. All AEs had already been identified in previous clinical trials or observational studies. The incidence of AEs leading to discontinuation (4.2%) and serious AEs (4.9%) observed in this study were consistent with the known safety profile of brodalumab [31]. Furthermore, randomized clinical trials of IL-17 and IL-23 inhibitors reported AEs in 57% of patients (95% CI 0.55–0.59) after 12 weeks, 52% (95% CI 0.49–0.55) after 16 weeks, 72% (95% CI 0.66–0.78) after 24 weeks, and 81% (95% CI 0.76–0.86) after 52 weeks, respectively [32]. An observational series reported significantly lower rates of severe/discontinuation events expressed as percentages or events per 100 patient-years [33].

Real-life studies describe an overall favourable safety profile, with respiratory infections, arthralgias, and skin and joint events reported. Arthralgia was the most common AE motivating discontinuation in a cohort (main reason for discontinuation among 24.2% of patients who discontinued treatment) [34]. An Italian retrospective series reported that brodalumab was safe in routine practice with no major new safety signals, and that treatment was discontinued for AEs in 11.5% of patients in a 24-week study [24] and without new safety signals after 36 months in a large cohort of 606 patients [35]. In this study, treatment discontinuation was observed in 4.2% of patients. Safety data underscore the favourable safety profile of brodalumab in real-world clinical practice. Nevertheless, it would be interesting to correlate safety data with drug survival data to provide a detailed description of the reasons for discontinuation (ineffectiveness vs. AEs).

At baseline, certain patient characteristics were associated with higher disease severity and poorer quality of life, particularly in bioexperienced patients, those with multiple high-impact psoriasis areas, and those with overweight or obesity. These findings are consistent with existing literature, which has highlighted the impact of comorbidities, such as obesity, and prior biologic exposure on treatment outcomes in psoriasis [9,10,11]. In our study, bioexperienced patients, who had previously failed or been exposed to other biologic therapies, exhibited a higher baseline DLQI, suggesting that these patients may experience greater disease burden despite prior treatments. The presence of multiple HIAs further complicates treatment response, underlining the need for individualized treatment strategies in these subgroups.

Brodalumab demonstrates effectiveness and safety in the treatment of moderate-to-severe psoriasis in real-world clinical practice. The results of this study provide further support for the use of brodalumab in diverse patient populations, including those with comorbidities or high-impact areas of psoriasis. Some subgroup analyses focused on relatively small numbers, potentially affecting statistical robustness. Future studies should explore the long-term effects of brodalumab in these specific subgroups to refine treatment strategies and improve patient outcomes in psoriasis management.

Influence of BMI on the Effectiveness of Brodalumab

A prospective study of over 8000 patients estimated that individuals with a BMI > 30 have a 71% increased risk of developing psoriasis [36]. In France, the prevalence of obesity is notably higher among patients with psoriasis compared to the general population [37]. Moreover, it has been well documented that obesity can diminish the effectiveness of treatments, largely due to the associated inflammation and the distribution of inflammatory mediators in adipose tissue [9,10,11]. Despite this, availability of data on the effectiveness of brodalumab in patients with obesity in real-world settings remains limited.

Previous studies have indicated that biologic therapies are associated with an increased risk of treatment failure in patients with obesity. A prospective multicentre study of nearly 3000 patients treated with various biologics (anti-TNF, anti-IL-17, anti-IL-12/23, and anti-IL-23) found a 30% reduction in the likelihood of achieving PASI 90 in patients with obesity [38]. This highlights the challenges faced by patients with obesity in achieving optimal therapeutic outcomes with biologic therapies. However, a recent review suggested that brodalumab remains an effective and safe treatment option for these patients, offering the potential for skin clearance and improvement in quality of life despite the presence of obesity-related treatment challenges [39].

In the PSO-TARGET cohort, a correlation between BMI and baseline mean DLQI score was observed, suggesting that psoriasis has a more profound impact on the quality of life of patients with overweight and obesity, compared to those with normal BMI. This finding underscores the importance of considering BMI when evaluating psoriasis severity and choosing treatment. Notably, by W52, 62.5% of patients with overweight and 48.6% of patients with obesity in our cohort achieved complete clearance of psoriasis, further supporting the effectiveness of brodalumab in these groups. Additionally, approximately 80% of patients with overweight or obesity experienced improvements in quality of life, as evidenced by DLQI scores, by as early as W12/16 and sustained through to W52. No significant differences were observed between the BMI groups, suggesting effectiveness of brodalumab regardless of BMI.

Our real-world data confirms that brodalumab is not only an effective treatment for psoriasis in patients with overweight and obesity but also offers sustained long-term benefits, both in terms of skin clearance and quality of life improvements. In line with recent German data, this supports brodalumab as a valuable therapeutic option for patients with overweight or obesity, who may otherwise face reduced treatment effectiveness with alternative biologic agents [40].

Impact of Bioexperience on the Effectiveness of Brodalumab

Patients with prior biologic treatment exposure may experience a reduced likelihood of responding to subsequent biologic therapies compared to treatment-naïve patients. Repeated exposure to biologics can alter the immune system’s response, potentially diminishing the effectiveness of subsequent treatments [10,11,12]. However, recent reviews of available biologics have indicated that bioexperienced patients can still achieve favourable outcomes, particularly with anti-IL-17 and anti-IL-23 therapies [41].

In the PSO-TARGET cohort, the effectiveness of brodalumab was significantly slightly lower in bioexperienced patients compared to bionaïve patients. Nevertheless, over half of the bioexperienced patients achieved complete skin clearance by W52, suggesting that brodalumab remains an effective treatment option even in patients with prior biologic exposure. Furthermore, brodalumab improved the quality of life for bioexperienced patients. By W12/16, more than half of the bioexperienced patients achieved a reduction of at least 4 points in their DLQI score, a clinically meaningful change. At W52, approximately two-thirds of bioexperienced patients achieved a DLQI score of < 1, suggesting that brodalumab improved quality of life. In parallel, brodalumab also appeared to be an interesting treatment for bionaïve patients: 65.5% of them achieved skin clearance and 75.0% achieved DLQI ≤ 1 at W52.

Given that quality of life is a key factor in treatment decision-making for patients with psoriasis [21], these findings underscore the importance of brodalumab as an effective therapeutic option for patients who have previously received biologic treatments. It offers not only skin clearance but also notable improvements in quality of life, addressing an important unmet need in this patient population. In bioexperienced patients, analysing drug survival data is of particular interest. A recent meta-analysis provided an overview of available drug survival studies regarding IL-17 and IL-23 inhibitors. This meta-analysis revealed that IL-17 and IL-23 inhibitors generally exhibit high drug survival rates. Notably, drug survival estimates were higher in bionaïve patients compared to those who had prior exposure to biologic treatments [42]. In the PSO-TARGET cohort, the drug survival data align with these findings. Drug survival remained high in both bionaïve and bioexperienced patients over the 52-week follow-up period, though lower rates were observed in bioexperienced patients.

Brodalumab showed effectiveness in bioexperienced and bionaïve patients. In a recent German real-world evidence study, effectiveness of brodalumab was confirmed in relevant subgroup analysis according to previous treatment (bionaïve and different prior biologics) [43]. However, a more detailed analysis of treatment effectiveness based on specific prior biologics could provide further insights into the potential of brodalumab and particularly on the positioning of brodalumab in the therapeutic strategy for psoriasis.

Effectiveness of Brodalumab According to High-Impact Areas at Baseline

Certain body areas, including the genitals, nails, scalp, and intertriginous regions, are considered as high-impact areas. Patients with psoriasis affecting these areas often face challenges in applying topical treatments, experience greater stigmatization, and report an impact on their quality of life. Notably, this impact on quality of life can persist even when overall psoriasis scores improve [44]. Biologic therapies have shown effectiveness in addressing psoriasis in HIAs, with growing evidence supporting the beneficial effects of brodalumab in these contexts [44].

In the PSO-TARGET cohort, nearly 85% of patients presented with one or more HIAs at baseline. These patients exhibited higher values for BSA, PASI, and DLQI, reflecting the heightened disease burden. Despite this, brodalumab remained effective in these patients, regardless of the number of HIAs at baseline. Quality-of-life data further underscore the utility of brodalumab, with approximately 80% of patients with ≥ 2 HIAs achieving a reduction of at least 4 points in their DLQI scores from W12/16, sustained through W52. Drug survival data support the effectiveness of brodalumab, showing high drug survival rates in patients regardless of the number of HIAs at baseline.

These findings highlight the value of brodalumab as an effective treatment option for patients with psoriasis involving one or more HIAs, addressing both clinical severity and quality-of-life outcomes. Further analysis on outcomes by specific types of high-impact areas (scalp, nails, genital, etc.) would strengthen the effectiveness of brodalumab in these subgroups of patients.

Effectiveness of Brodalumab in Older Patients (≥ 65 Years)

Currently, there is a paucity of real-world data on the effectiveness and safety of brodalumab in older patients with psoriasis (≥ 65 years) [17]. Treating psoriasis in older adults poses unique challenges due to the increased prevalence of comorbid conditions and the effects of immunosenescence [45]. A recent systematic review reported similar effectiveness for biologic therapies across all classes between nonolder adult and older patients [45]. Additionally, a more recent retrospective multicentre real-world study demonstrated that brodalumab maintains comparable effectiveness to that observed in randomized controlled trials and exhibits an acceptable safety profile even in older patients [17].

In the PSO-TARGET cohort, 18.9% of patients were classified as older. These patients had a longer disease history but exhibited lower mean PASI and DLQI scores at baseline compared to younger patients. While the effectiveness of brodalumab in older patients was slightly lower in terms of PASI improvement and DLQI reduction, the proportions of older and younger patients achieving DLQI ≤ 1 during the follow-up period were similar, 65.2% and 74% respectively. In a recent retrospective study on 121 patients with moderate-to-severe plaque psoriasis treated with secukinumab, ixekizumab, guselkumab, or risankizumab, a significant delayed initial response was observed in older patients [46]. With brodalumab, our data revealed no significant difference from week 12/16 regardless of age group. AEs were not observed to be more frequent or severe in older patients (Supplementary materials Table 4); 3.7% of patients aged ≥ 65 years discontinued treatment, compared to 4.2% in the overall cohort. Similarly, infections were not more frequent in older patients, occurring in 3.7% of those aged ≥ 65 years versus 4.9% in the entire cohort. These findings suggest that the safety profile of brodalumab is consistent across age groups. Our analysis confirms the safety and effectiveness of brodalumab in real life in older patients who have sometimes several comorbidities and are often poorly represented in clinical trials. Brodalumab thus emerges as a promising treatment option for older patients with psoriasis, offering substantial improvements in quality of life. However, further studies focusing on this specific subpopulation are warranted to confirm and expand upon these findings.

Strengths and Limitations

The study’s strengths lie in its real-world setting, providing insights into the effectiveness and safety of brodalumab in a diverse cohort of patients, including those often excluded from randomized controlled trials. However, limitations of the study include its observational design, post hoc statistical analyses, the lack of a control group, and the potential for selection bias, as patients were included on the basis of the clinician’s decision to initiate brodalumab treatment. Despite these limitations, the data offer valuable insights into the long-term outcomes of brodalumab in routine clinical practice.

Brodalumab blocks signalling pathways involving five IL-17 isoforms, all implicated in psoriasis pathogenesis [3, 4]. Nevertheless, studies revealed various genetic profiles of the patients with psoriasis and other cytokines, such as the IL-20 family, play a significant role in this variation [47,48,49]. In parallel, some other immune-regulating genes [50] seemed to be involved in psoriasis. In this observational study, the genetic profile of patients was unknown, while it could impact the brodalumab response.

In the PSO-TARGET cohort, we assessed and analysed drug survival both overall and across four specific subpopulations. Drug survival serves as a key indicator of the long-term effectiveness and safety of biotherapies in dermatology, often regarded as a reliable real-life measure of treatment success in psoriasis [42, 51]. Subgroups included bioexperienced, older patients, those with overweight or obesity, and those with ≥ 1 high-impact area. Evaluating drug survival beyond 52 weeks would provide further valuable insights. Nevertheless, as a result of the real-world setting, the number of patients in each subgroup was small (e.g. n = 27 for older and n = 47 for patients with obesity) making it more difficult to extrapolate conclusions for the overall population of patients with psoriasis. Moreover, our results were consistent with published data on brodalumab.

Within the PSO-TARGET cohort, a limited number of high-impact areas were documented at baseline, specifically the scalp, nails, intertriginous areas, and genitals. However, specific scoring tools such as the Physician’s Global Assessment of genitalia (PGA-G), Palmoplantar Psoriasis Area and Severity Index (ppPASI), Nail Psoriasis Severity Index (NAPSI), and Psoriasis Scalp Severity Index (PSSI) were not employed at baseline or during follow-up visits. While the data underscore the effectiveness of brodalumab in treating patients with high-impact areas, they do not allow for a precise evaluation of the drug’s impact on specific localizations.

Notably, previous studies have highlighted the benefits of brodalumab in improving palmoplantar psoriasis [29, 45]. However, palmoplantar locations were not accounted for in this study, representing a potential area for further investigation to better understand the localization-specific effects of brodalumab.