Bimekizumab safety in moderate to severe plaque psoriasis: Rates of hepatic events and changes in liver parameters over two years in randomized phase III/IIIb trials
Today's report also covers roflumilast foam, biologic failure in psoriasis, and more 1,700 words, 7 minutes, 30 seconds)
The Vender on Psoriasis e-newsletter is supported by an unrestricted grant from Sun Pharma Canada
Good morning and welcome to the thirteenth issue of Special Reports: Skin Spectrum Weekly presents “Vender on Psoriasis.” This series is based on Dr. Vender’s popular column appearing in each edition of The Chronicle of Skin & Allergy, which offers expert commentary and opinions on current clinical developments in PsO. We’d love to get your feedback and suggestions and invite you to be in touch. Please write to us at health@chronicle.org
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Bimekizumab safety in moderate to severe plaque psoriasis: Rates of hepatic events and changes in liver parameters over two years in randomized phase III/IIIb trials
This study in the Journal of the American Academy of Dermatology (April 6, 2024) evaluated the hepatic safety of bimekizumab, an IL-17A and IL-17F inhibitor, in patients with moderate to severe plaque psoriasis over two years across five phase III/IIIb trials. Patients with psoriasis are at increased risk of liver function abnormalities due to associated comorbidities such as obesity, diabetes, and dyslipidemia, as well as potential hepatotoxicity from certain systemic psoriasis treatments.
Data from 2,186 patients who received ≥1 dose of bimekizumab were analyzed. The exposure-adjusted incidence rate (EAIR) of hepatic treatment-emergent adverse events (TEAEs) over two years was 3.5 per 100 patient-years, with no increase from the first to second year. The two-year EAIRs of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) elevations >3x and >5x the upper limit of normal (ULN) were 2.3 and 0.6 per 100 patient-years, respectively, similar to placebo, adalimumab, secukinumab, and ustekinumab during controlled study periods.
Mean ALT and AST levels remained consistent over two years in bimekizumab-treated patients. Clinical markers of liver fibrosis, the Fibrosis-4 (FIB-4) Index and AST to Platelet Ratio Index (APRI), did not increase through two years, regardless of baseline fibrosis risk.
The majority of hepatic TEAEs were mild or moderate in severity, with low rates of severe (0.3/100 patient-years), serious (0.1/100 patient-years), and discontinuation-leading (0.3/100 patient-years) events over two years.
The study showed the rates of hepatic AEs with bimekizumab were consistent through two years, with incidences of transaminase elevations similar to comparators during controlled periods. Clinical markers of liver fibrosis did not increase in bimekizumab-treated patients, suggesting a favourable hepatic safety profile over two years.
Comment: This study provides valuable insights into the hepatic safety profile of bimekizumab in patients with moderate to severe plaque psoriasis over a two-year period. Given the increased risk of liver function abnormalities in psoriasis patients due to associated comorbidities and potential hepatotoxicity from systemic treatments, assessing the safety of new therapies is crucial.
The analysis of data from over 2,000 patients treated with bimekizumab revealed a low incidence rate of hepatic treatment-emergent adverse events (TEAEs) over the two-year period, with no significant increase over time. The rates of ALT and AST elevations were comparable to those observed with placebo and other psoriasis treatments during controlled study periods, indicating a similar hepatic safety profile.
Furthermore, the consistency of mean ALT and AST levels over two years and the lack of increase in clinical markers of liver fibrosis suggest a favourable hepatic safety profile for bimekizumab. The majority of hepatic TEAEs were mild or moderate in severity, with low rates of severe, serious, and discontinuation-leading events, further supporting the safety of bimekizumab in this regard.
Overall, these findings suggest that bimekizumab maintains a consistent and favourable hepatic safety profile over two years of treatment, providing reassurance for clinicians and patients considering this therapy for moderate to severe plaque psoriasis. No monitoring is required or suggested by product monograph or expert consensus.
Efficacy and safety of roflumilast foam 0.3% in adolescents and adults with seborrheic dermatitis
Roflumilast foam 0.3% is a novel, once-daily, steroid-free topical treatment that has demonstrated significant efficacy and favourable safety for seborrheic dermatitis in adolescents and adults in a recent study (J Am Acad Dermatol 2024 Jan 20; EPub ahead of print). In a phase III, randomized, double-blind, vehicle-controlled trial, 79.5% of patients treated with roflumilast foam achieved Investigator Global Assessment (IGA) success at week 8, defined as an IGA score of clear or almost clear plus a ≥2-grade improvement from baseline, compared to only 58.0% with vehicle (p<0.001). Roflumilast foam also showed superior IGA success rates at weeks 2 and 4.
Additionally, roflumilast foam provided rapid and significant reductions in erythema, scaling, and itch associated with seborrheic dermatitis. It was well-tolerated, with a low rate of treatment-related adverse events similar to vehicle. As a phosphodiesterase-4 inhibitor with anti-inflammatory properties, roflumilast represents a novel mechanism of action for treating seborrheic dermatitis, filling an unmet need for effective non-steroidal topical therapies. The foam vehicle enables easy application in hair-bearing areas like the scalp. Overall, these data support roflumilast foam 0.3% as a promising new topical treatment for seborrheic dermatitis in adolescents and adults.
Comment: The study highlights the promising efficacy and safety profile of roflumilast foam 0.3% as a novel, steroid-free topical treatment for seborrheic dermatitis in adolescents and adults. The phase III trial demonstrated significant improvement in Investigator Global Assessment (IGA) scores at week 8 compared to vehicle, with a high proportion of patients achieving success. Moreover, the foam exhibited superiority in IGA success rates at earlier time points and showed rapid reduction in key symptoms such as erythema, scaling, and itch.
Importantly, roflumilast foam was well-tolerated with a low rate of treatment-related adverse events, aligning with the safety profile of the vehicle. Its mechanism of action as a phosphodiesterase-4 inhibitor with anti-inflammatory properties presents a novel approach in the treatment of seborrheic dermatitis, addressing an unmet need for effective non-steroidal topical therapies. The foam formulation facilitates convenient application, particularly in hair-bearing areas like the scalp.
Overall, these findings suggest that roflumilast foam 0.3% holds promise as a valuable addition to the treatment armamentarium for seborrheic dermatitis, offering both efficacy and tolerability benefits for patients across different age groups. No other treatments in many years have become available or have been approved for this skin disorder.
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Sociodemographic and clinical characteristics associated with multiple biologic failure in psoriasis: A 2015-2022 prospective cohort analysis of the CorEvitas psoriasis registry
This prospective cohort study analyzed 1,039 psoriasis patients who initiated their first biologic therapy between 2015-2020 and had ≥24 months follow-up data. Published in the Journal of the American Academy of Dermatology (Nov. 2023; 974-983), a total of 47.2% had a good response by continuing their first biologic ≥2 years, while 6.3% experienced multiple biologic failure, defined as discontinuing ≥2 biologics of different classes due to inadequate efficacy despite ≥90 days use each.
Female sex (OR 2.13), shorter psoriasis duration (OR 0.59 per SD increase in years), earlier year of biologic initiation, prior nonbiologic systemic therapy use, history of hyperlipidemia (OR 2.02), and Medicaid insurance (OR 3.31) were significantly associated with higher odds of multiple biologic failure versus good response.
The most common biologic sequence in multiple biologic failure patients was a tumour necrosis factor-α inhibitor followed by an interleukin-17 inhibitor. At last follow-up, mean PASI scores were 1.0 and 4.8 for good response and multiple biologic failure groups, respectively, compared to 10.0 and 9.4 at baseline.
Approximately 6% of psoriasis patients met the criteria for multiple biologic failure. Female sex, shorter disease duration, earlier biologic initiation year, prior systemic therapy, hyperlipidemia, and Medicaid insurance increased the odds of multiple failures. The investigators noted that the tumour necrosis factor-α to interleukin-17 inhibitor sequence was most common in multiple failures, and multiple failures had higher disease activity scores at last follow-up versus good responders.
In summary, this study identified sociodemographic and clinical factors present at biologic initiation associated with higher risk of poor therapeutic response across multiple biologic classes in psoriasis. These characteristics may help stratify patients warranting more frequent monitoring.
Comment: This prospective cohort study sheds light on factors associated with therapeutic response to biologic therapy in psoriasis patients. The findings suggest that nearly half of patients maintain a good response to their first biologic over a two-year period, while a small percentage experience multiple biologic failures, defined as inadequate efficacy despite trying at least two biologics of different classes.
The study identifies several factors linked to higher odds of multiple biologic failure, including female sex, shorter psoriasis duration, earlier initiation of biologic therapy, prior use of nonbiologic systemic therapies, history of hyperlipidemia, and Medicaid insurance. Interestingly, the most common sequence of biologics in patients with multiple failures involved a tumour necrosis factor-α inhibitor followed by an interleukin-17 inhibitor.
At the last follow-up, patients with multiple biologic failures exhibited higher disease activity scores compared to those with a good response, underscoring the challenges faced by this subgroup of patients. The study underscores the importance of identifying sociodemographic and clinical factors at biologic initiation that may predict poor therapeutic response, aiding in the stratification of patients who may require closer monitoring or alternative treatment approaches.
Overall, this study provides valuable insights into the real-world effectiveness of biologic therapies in psoriasis and highlights the need for personalized treatment strategies to optimize outcomes in patients with varying risk profiles. This also reflects real world experience.
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If you find the contents of this newsletter interesting, please check out the Vender on Psoriasis podcast. It’s available at Apple iTunes, Stitcher, Spotify, or wherever you get your podcasts.
Dr. Ron Vender is a Hamilton-based certified dermatologist with over 30 years of clinical practice experience and over 100 clinical trials in psoriasis. He is founder and director of Dermatrials Research Incorporated and Venderm Consulting, specializing in treatments and management solutions for individuals with psoriasis.
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