Detailed Information

Ixekizumab is a humanized IgG4 mAb that selectively binds with the IL-17A cytokine and inhibits its interaction with the IL-17 receptor. IL-17A is a naturally occurring cytokine involved in normal inflammatory and immune responses. Ixekizumab inhibits the release of proinflammatory cytokines and chemokines.1

No head-to-head trials have been conducted comparing the efficacy and safety of ixekizumab to that of risankizumab in the treatment of psoriasis.

Since clinical trials are conducted under widely varying and controlled conditions, efficacy outcomes and adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Risankizumab-rzaa is a humanized IgG1 mAb that selectively binds to the p19 subunit of the human IL-23 cytokine and inhibits its interaction with the IL-23 receptor. IL-23 is a naturally occurring cytokine that is involved in inflammatory and immune responses. Risankizumab-rzaa inhibits the release of proinflammatory cytokines and chemokines.2

Adjusted Indirect Comparison of Ixekizumab and Risankizumab in Plaque Psoriasis

The methodology used to indirectly compare the primary efficacy outcomes (PASI 75 and PASI 90) of ixekizumab and risankizumab in patients with moderate-to-severe psoriasis were

AIC using the Bucher method, and
MAIC using the Signorovitch method, which is an extension of AIC taking into account differences in baseline characteristics and/or treatment effect modifiers matched to the means of the characteristics available in the literature.3

Both methods of indirect comparisons used are subject to limitations including the potential for bias due to differences between trial populations and imbalances in unobserved factors between trials. These limitations can only be avoided with head-to-head randomized trials.4,5

As shown in Study Design for Indirect Comparison of Ixekizumab and Risankizumab, ustekinumab and placebo were used as the common comparators for the indirect comparison of ixekizumab and risankizumab.3

Study Design for Indirect Comparison of Ixekizumab and Risankizumab3

The risk difference for PASI responses are available in

Ixekizumab vs Risankizumab Indirect Comparison of PASI 75 Responses at Week 12 Via Comparator Bridges
Ixekizumab vs Risankizumab Indirect Comparison of PASI 90 Responses at Week 4 Via Comparator Bridges
Ixekizumab vs Risankizumab Indirect Comparison of PASI 90 Responses at Week 8 Via Comparator Bridges, and
Ixekizumab vs Risankizumab Indirect Comparison of PASI 90 Responses at Week 12 Via Comparator Bridges.

The authors concluded that indirect comparison across multiple analysis methods using a placebo comparator bridge indicated that ixekizumab provides clinical benefits over risankizumab in terms of PASI 75 and PASI 90 response and with regard to speed of action up to week 12 in patients with moderate-to-severe psoriasis.3

In the ustekinumab bridge, efficacy analysis was performed on a smaller sample size (256 unmatched ixekizumab-treated patients compared to 1952 unmatched ixekizumab-treated patients in the placebo bridge) which may have led to less precise results.3

Ixekizumab vs Risankizumab Indirect Comparison of PASI 75 Responses at Week 12 Via Comparator Bridges3

Ixekizumab vs Risankizumab Indirect Comparison of PASI 90 Responses at Week 4 Via Comparator Bridges3

Ixekizumab vs Risankizumab Indirect Comparison of PASI 90 Responses at Week 8 Via Comparator Bridges3

Ixekizumab vs Risankizumab Indirect Comparison of PASI 90 Responses at Week 12 Via Comparator Bridges3

References

1Taltz [package insert]. Indianapolis, IN: Eli Lilly and Company; 2021.

2SKYRIZI [package insert]. North Chicago, IL: AbbVie Inc; 2019.

3Gottlieb A, Ramot Y, Smith S, et al. Indirect comparison of ixekizumab versus risankizumab for up to 12 weeks of treatment in patients with moderate-to-severe psoriasis. Poster presented at: 77th Annual Meeting of the American Academy of Dermatology; March 1-5, 2019; Washington, DC. https://www.aad.org/eposters/Submissions/getFile.aspx?id=9775&type=sub

4Bucher HC, Guyatt GH, Griffith LE, et al. The results of direct and indirect treatment comparisons in meta-analysis of randomized controlled trials. J Clin Epidemiol 1997;50(6):683-691. https://doi.org/10.1016/S0895-4356(97)00049-8

5Signorovitch JE, Wu EQ, Yu AP, et al. Comparative effectiveness without head-to-head trials: a method for matching-adjusted indirect comparisons applied to psoriasis treatment with adalimumab or etanercept. Pharmacoeconomics. 2010;28(10):935-945. http://dx.doi.org/10.2165/11538370-000000000-00000

Glossary

AIC = adjusted indirect comparison

IgG1 = immunoglobulin G subclass 1

IgG4 = immunoglobulin G subclass 4

IL = interleukin

mAb(s) = monoclonal antibody

MAIC = matched-adjusted indirect comparison

PASI = Psoriasis Area and Severity Index

PASI 75 = 75% improvement from baseline in Psoriasis Area and Severity Index

PASI 90 = 90% improvement from baseline in Psoriasis Area and Severity Index

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Ixekizumab: Comparison With Risankizumab in Psoriasis