Positive effects are seen in both Psoriasis Area and Severity Index (PASI) score and symptoms of depression in psoriasis patients with an insufficient response to tumor necrosis factor-alpha inhibition (TNF-α) and switch to interleukin 17 inhibition through brodalumab, according to recent findings.¹

This new research was viewed as useful, given that psoriasis has been linked to several different comorbidities including increased cardiovascular disorders, psoriatic arthritis, and depression.² Psoriasis treatment and its association with mental health outcomes was acknowledged by the study’s investigators as less established.³

The investigators—led by Ylva Andersch-Björkman, from the University of Gothenburg’s Department of Dermatology and Venereology at the Institute of Clinical Sciences, Sahlgrenska Academy—noted that while tools for mental health assessment exist, there are not any that are used by default in dermatology.

“Therefore, two different tools were selected for use in our study: the Self-assessment Montgomery-Asberg Depression Rating Scale (MADRS-S) for depression and the Hospital Anxiety and Depression Scale (HADS) covering both depression and anxiety,” Andersch-Björkman and colleagues wrote. “Both questionnaires correlate reasonably well with expert ratings.”

Background and Findings

The investigators conducted their research in several different clinics located in Sweden known to actively prescribe biologics for patients. The study’s participants were found consecutively in outpatient clinic settings located at the Department of Dermatology and Venereology in University Hospitals found in both Gothenburg and Malmö, in addition to other hospitals with dermatology departments.

The research team’s data collection period took place between December 2018 and January 2020. In order for participants to be eligible, the individuals had to have been given TNF-α treatment for a minimum of 4 months and have shown an absolute PASI of over 7 or a PASI score ranging from 3 - 7 combined with a DLQI higher than 5, with either being at the time of inclusion.

The team required the participants to be 18 years old at least, as well as proficient in Swedish and without any major mental or cognitive impairments. The investigators used an open-label, parallel-group, randomized, multicenter, phase 4 study design in order to determine the efficacy of brodalumab for participants with reported moderate-to-severe plaque psoriasis who had also not responded correctly to TNF-α inhibition.

The study’s participants were randomly assigned using a 1:1 ratio to be treated with brodalumab as per the product characteristics. This was 210 mg at weeks 0, 1, 2, then followed by 210 mg at every 2 weeks for 12 weeks for the brodalumab arm, but participants would continue TNF-α for a further 12 weeks prior to brodalumab transition in the TNF/brodalumab arm.

Among those in the TNF/brodalumab patient group, the investigators’ assessments took place at the outset of their research at weeks 8 and then 12. The participants’ switch to brodalumab occurred at the 12th week, or earlier if the severity of their disease indicated its necessity.

Following the participants’ screening phase, the final cohort ended up with a total of 20 participants, 70% of which were men. Interestingly, 3 participants decided to discontinue their part in the research for varying reasons, including 1 having reported joint pain, another with travel constraints, and the third showing signs of unspecified stomach problems at the time of the TNF-α treatment.

The research team used PASI, Static Physician's Global Assessment (sPGA), the Patient Global Assessment form (PaGA), the Pruritus Visual Analogue Scale (VAS), and DLQI as assessment tools for the participants.

Overall, after a 12-week course of treatment using brodalumab, the investigators reported notable enhancements in the participants’ mean scores of sPGA, PASI, PaGA, Pruritus VAS, DLQI, and MADRS-S. They also added that while they did see improvements in HADS-D and HADS-A scores, these improvements were shown not to have reached statistical significance.

The team showed that following 12 weeks of brodalumab treatment, only a single participant was shown to have scored as depressed. The investigators concluded that when TNF-inhibitors are shown to be insufficient in their efficacy, use of brodalumab as an alternative is effective as an approach to improving life quality.

Their data align well with their anticipated outcomes and form the basis for the Swedish guidelines related to the management of the skin disease. The investigators added that the swift and strong response seen in HADS-A, MADRS-S, and HADS-D demonstrated the value of considering mental health in decisions for patients.

For Swedish guidelines specifically, this insight could prompt earlier consideration of more potent treatments such as brodalumab for certain patients as opposed to the current criteria.

Furthermore, the research team noted that the response to treatment in participants’ scores for DLQI, HADS-D, HADS-A, and MADRS-S suggested a similar trend among those with less than 75% and greater than or equal to 75% improvement in their PASI score.

The team added that such a trend indicates greater evidence that IL-17 inhibition could directly affect both depression and anxiety, not only through indirect psoriasis improvement.

“These results are fully in line with expectations and reflect the basis for the Swedish guidelines for psoriatic treatment,” they wrote. “In addition, we found that the change of treatment had positive effects on anxiety and depression symptoms. This is in line with other studies.”

References

1. ^{Andersch-Björkman, Y, Micu, E, Seifert, O, Lonne-Rahm, S-B, Gillstedt, M, Osmancevic, A. Effects of brodalumab on psoriasis and depressive symptoms in patients with insufficient response to TNF-α inhibitors. J Dermatol. 2023; 00: 1–14. https://doi.org/10.1111/1346-8138.16917.}
2. ^{Elmets C, Leonardi C, Davis DMR, Gelfand J, Lichten J, Mehta NN, et al. Joint AAD-NPF guidelines of care for the management and treatment of psoriasis with awareness and attention to comorbidities. J Am Acad Dermatol. 2019; 80: 1073–1113.}
3. ^{Lotrich FE, El-Gabalawy H, Guenther LC, Ware C. The role of inflammation in the pathophysiology of depression: different treatments and their effects. J Rheumatol Suppl. 2011; 88: 48–54.}