Izokibep for the treatment of moderate-to-severe plaque psoriasis
Today's report also covers fractures and falls in psoriatic arthritis patients, efficacy and safety of apremilast, and more (1,600 words, 6 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 tenth 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
Izokibep for the treatment of moderate-to-severe plaque psoriasis
This phase II study, known as AFFIRM-35, assessed the dose response, efficacy, and safety of izokibep, an interleukin (IL)-17A inhibitor, in patients with moderate-to-severe plaque psoriasis who had inadequate responses to two or more standard therapies.
Published in the British Journal of Dermatology (doi.org/10.1093/bjd/ljad186), 109 adult patients were enrolled in the study and randomized into five groups: placebo, izokibep 2 mg, 20 mg, 80 mg, or 160 mg, administered every two weeks for 12 weeks. After this initial phase, patients initially receiving placebo were switched to izokibep 80 mg, and dosing intervals for all patients were adjusted based on Psoriasis Area and Severity Index (PASI) scores. The core study was followed by two optional one-year extension periods, resulting in a total study duration of three years.
The primary endpoint was the achievement of a 90% reduction in PASI score (PASI 90) at week 12. Results indicated that PASI 90 response rates increased in a dose-dependent manner, with rates of 0%, 5%, 19%, 71%, and 59% for the placebo, 2 mg, 20 mg, 80 mg, and 160 mg izokibep groups, respectively, at week 12. Rapid dose-dependent improvements were also observed across other efficacy outcomes.
During the placebo-controlled period, adverse events (AEs) in the izokibep groups were generally similar to placebo, except for mild injection site reactions. AEs were predominantly mild to moderate, and the drug was well tolerated.
Izokibep maintained its efficacy at higher dosage levels for up to three years, with no emergence of new safety signals. These findings suggest that izokibep is well-tolerated and effective in treating plaque psoriasis. Higher doses or more frequent dosing may further enhance response rates.
Comment: There could never be enough biologics to treat our patients as some come and some disappear depending on economics and adverse events associated with these medications. In this case there is a new interleukin 17 inhibitor called izokibep. This again shows the power of interleukin 17 inhibitors by having an extremely high PASI-90 response with this drug. Because this is an early phase study, the dosing has not been finally determined. Although interleukin 23 inhibitors affect the master cytokine, interleukin 23, the end result is always reducing interleukin 17 which these interleukin 17 inhibitors, such as secukinumab, ixekizumab, bimekizumab, and brodalumab directly attack. Phase III studies will determine how izokibep reacts in the larger population.
Fractures, falls in patients with PsA
The study in The Journal of Dermatology (DOI: 10.1111/1346-8138.16710) explored bone mineral density (BMD), the 10-year fracture risk, the number of prevalent fractures, and the frequency of falls in relation to psoriatic arthritis (PsA) disease characteristics in a cohort with PsA.
A total of 61 PsA patients and 69 consecutive, age-matched controls underwent a physical examination, bone mineral density (BMD, and T-score) assessments, and calculation of a 10-year fracture risk. The odds ratio (OR) for low BMD and the 10-year risk of hip fracture was higher (p=0.0029; 0.0002, p<0.001, OR=21,9, p=0.014) in the PsA group. According to the investigators, the PsA patients were more predisposed to prevalent fractures, including peripheral and vertebral fractures, and falls (OR 3.42; 2.26; 13.33; 2.95, respectively), compared to the control group.
Scalp psoriasis and late-onset psoriasis were significantly associated with a great number of prevalent fractures (p=0.0049; 0.029), and the number of falls per year correlated with late-onset psoriasis and flexural psoriasis (p=0.007; 0.023).
The authors conclude that PsA is an independent risk factor for reduced bone density and falls, resulting in related bone fractures. Patients with late-onset psoriasis are more likely to experience falls and related fractures, particularly if their disease involves the scalp and body folds.
Comment: This study looked at another comorbidity that may be associated with psoriasis and psoriatic arthritis. A bone mineral density test was performed, and the 10-year fracture risk was examined. A very high odds ratio for low bone mineral density and 10-year risk of hip fracture was seen in the psoriatic arthritis group. This study confirmed that psoriatic arthritis patients were more predisposed to fracture and reduction in bone mineral density. In addition, scalp psoriasis and late onset psoriasis was associated with more fractures as well. The authors concluded that psoriatic arthritis was an independent risk factor for reduced bone density and potentially fractures.
This tells us that a new comorbidity such as osteoporosis that was not previously recognized in psoriatic disease may be important to examine, especially in late onset psoriasis or those who have psoriatic arthritis. This may prevent additional morbidities such as hip fractures, or other factors that can lead to further complications. Certainly further studies are required, however, primary care practitioners or other specialists associated with osteoporosis may consider testing bone mineral density in patients with psoriatic arthritis.
Efficacy and safety of apremilast in patients with limited skin involvement, plaque psoriasis in special areas and impaired quality of life: Results from the EMBRACE randomized trial
This study, published in the Journal of the European Academy of Dermatology and Venereology (DOI: 10.1111/jdv.18689), evaluated the impact on QoL, efficacy, and safety of apremilast 30 mg b.i.d. in patients with limited skin involvement with plaque psoriasis manifestations in special areas (including visible locations scalp, nails, genital reas, or palmoplantar areas) and impaired QoL.
All 277 patients included in this phase 4, randomized, placebo-controlled, multinational study had plaque psoriasis not controlled by topical therapy; lack of response, contraindication, or intolerance to conventional first-line systemic therapy; psoriasis in ≥1 special areas; Psoriasis Area and Severity Index (PASI) ≥3 to ≤10; and Dermatology Life Quality Index (DLQI) >10. The primary endpoints was DLQI response (≥4-point reduction) at Week 16.
Of the 277 randomized patients (apremilast: n=185; placebo: n=92), a total of 221 completed Week 16 (apremilast: n=152; placebo: n=69). The authors report the primary endpoint (≥4-point reduction in DLQI at Week 16) was met by significantly more patients receiving apremilast (73.3%) vs. placebo (41.3%; p<0.0001). They also note that significantly greater improvement in affected body surface area (BSA) and PASI was observed with apremilast vs. placebo at Week 16 as well as in itch numeric rating scale (-2.5 vs -0.9, p<0.0001), skin discomfort/pain visual analog scale (-21.5 vs. -5.4, p=0.0003), and greater achievement of Patient Benefit Index ≥1 (77% vs. 40%, p<0.0001) at Week 16. No new safety signals were observed. The authors conclude that apremilast significantly improved skin-related QoL in patients with limited skin involvement with plaque psoriasis in special areas and highly impaired QoL. They note the safety profile was consistent with previous apremilast studies.
Comment: Apremilast is an excellent choice for patients who require or demand oral therapy that is safe and effective without the need for blood monitoring or concerns associated with the adverse events seen with traditional systemics such as cyclosporine, methotrexate, and acitretin. This study looks at severe quality of life impairment, and one or more special site involvement but a PASI between 3 and 10 in these patients. This important endpoint achieved by this study was the significant improvement in DLQI as early as week 16. Other important endpoints met included reduction in itch as well as reduction in BSA and PASI score. This re-emphasizes the facts that apremilast is a useful and beneficial oral anti-psoriatic option for patients who prefer oral therapy.
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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