More Rapid Improvement Seen With Ixekizumab vs Guselkumab for Plaque Psoriasis

Psoriasis is a chronic disease that affects 2% to 3% of men and women.2 The disease is characterized by plaques and reddish scaly patches. Some women develop pustular psoriasis, which can be life-threatening if severe.3 Although most women with psoriasis notice symptom improvement during pregnancy, 10% to 20% have symptom deterioration.3 The effect of psoriasis on fetal health is unclear.2 Some studies have suggested that psoriasis, which is a TH1-driven disease, contributes to lower birth weight as observed in other TH1-driven diseases.2 The proposed negative effects of psoriasis on fetal health are usually linked to moderate or severe psoriasis. Topical corticosteroids are safe to use during pregnancy, but topical tar products, tazarotene, and retinoids are teratogenic and should be avoided.2,7 Ultraviolent B phototherapy is safe in pregnant women with moderate to severe psoriasis but may compromise folate levels.2 Limited data are available about the safety of biologics during pregnancy, and careful consideration is required before prescribing.2,7
Ixekizumab provided complete skin clearance and improved quality of life in patients with plaque psoriasis by week 12 of a comparison study with guselkumab.

The superiority of ixekizumab vs guselkumab for rapidly improving the symptoms of moderate to severe plaque psoriasis was supported by results from a comparison study published in the British Journal of Dermatology, Safety signals were comparable in the ixekizumab and guselkumab trial arms.   

The IXORA-R study was a randomized, double-blind trial which compared the efficacy of interleukin (IL)-17 inhibitor ixekizumab with IL-23 inhibitor guselkumab. Eligible patients were ≥18 years of age with moderate to severe plaque psoriasis, defined per 3 criteria: (1) Global Assessment of Disease (sPGA) score of ≥3; (2) Psoriasis Area and Severity Index (PASI) ≥12; and (3) ≥10% body surface area affected. Patients were randomly assigned 1:1 to receive subcutaneous ixekizumab or guselkumab injections for 12 weeks. Injections were administered biweekly at approved doses (80-160 mg for ixekizumab; 100 mg for guselkumab). The primary endpoint was 100% improvement in PASI at week 12. As secondary endpoints, investigators also assessed achievement of 50%, 75%, or 90% improvement in PASI and complete clearance on sPGA. The Cochran-Mantel-Haenszel test was used to calculate the odds of obtaining study endpoints with ixekizumab vs guselkumab. Safety events were monitored throughout the trial duration.

A total of 1027 patients were randomly assigned to receive treatment: 507 to guselkumab and 520 to ixekizumab. The majority (94%) of patients completed 12 weeks of treatment. Mean age at enrollment was 49.0 ± 14.4 years, and 37% were women. At week 12, PASI 100 was achieved by 41% of the ixekizumab group, compared with 25% of the guselkumab group (odds ratio [OR], 2.14; 95% CI, 1.63-2.81; P <.001). Compared with the guselkumab group, greater percentages of the ixekizumab group obtained PASI 50 response at week 1 (OR, 4.73; 95% CI, 3.13-7.13), PASI 75 response at week 2 (OR, 6.26; 95% CI, 3.89-10.08), PASI 90 response at week 4 (OR, 3.21; 95% CI, 2.15-4.78), and PASI 100 response at week 4 (OR, 5.35; 95% CI, 2.33-12.28) (all P <.001). Complete clearance on sPGA was also more common in the ixekizumab arm (OR, 2.15; 95% CI, 1.64-2.82; P <.001).

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Treatment-emergent adverse events occurred with similar frequencies across study arms. Upper respiratory tract infection occurred in 7% each of the ixekizumab and guselkumab groups, and injection site reactions occurred slightly more commonly in patients treated with ixekizumab vs guselkumab (13% vs 3%). All injection site reactions were mild to moderate in severity.

As some of the study limitations, the researchers cited that patients were only from North America and that the study was not powered to permit a comparison of frequency of safety events.

These data support the efficacy of ixekizumab in achieving short-term improvements for moderate to severe plaque psoriasis. “The results suggest ixekizumab can deliver patients more rapid complete skin clearance and improved quality of life compared to guselkumab,” investigators wrote.

Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.

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Blauvelt A, Papp K, Gottlieb A, et al. A head-to-head comparison of ixekizumab versus guselkumab in patients with moderate-to-severe plaque psoriasis: 12-week efficacy, safety, and speed of response from a randomized, double-blinded trial [published online December 30, 2019]. Br J Dermatol. doi: 10.1111/bjd.18851