Psoriasis Biologics: IL-17 vs IL-23 Inhibitors in Head-to-Head Trials

Selecting Between IL-17 and IL-23: Clinical Framework

IL-17 inhibitors offer faster onset (measurable within 1-2 weeks), making them preferred when rapid clearance is clinically important. IL-23 inhibitors offer superior durability with less frequent dosing and rising efficacy over time, making them ideal for long-term maintenance. For patients with concomitant psoriatic arthritis, both classes are effective, but IL-17 inhibitors have more extensive joint data. IL-17 agents are contraindicated in active inflammatory bowel disease (risk of IBD flare), making IL-23 inhibitors the preferred choice in patients with comorbid Crohn disease or ulcerative colitis.

Safety and Monitoring Considerations

Both IL-17 and IL-23 inhibitor classes have favorable long-term safety profiles based on 5+ years of extension study data. Neither class requires routine laboratory monitoring. The main differentiators are candidiasis risk (higher with IL-17, especially bimekizumab) and the theoretical IBD risk with IL-17 agents. Infection rates are comparable to TNF inhibitors without the elevated tuberculosis reactivation risk. For atopic dermatitis, dupilumab and JAK inhibitors offer additional options. Pre-treatment screening should include hepatitis B/C serologies, tuberculosis testing, and assessment for IBD symptoms. Live vaccines should be avoided during active treatment with either class.

Talking to Patients About Treatment Goals

Many psoriasis patients have lived for years with the expectation that their skin will never be fully clear. Biologic therapy has changed this reality, and setting appropriate goals at the outset matters. In the era of IL-17 and IL-23 inhibitors, the treatment target should be near-complete clearance — not "better than before" but a skin state where the disease does not interfere with daily life, clothing choices, or self-image. Patients should understand that it may take several months to see the full benefit (particularly with IL-23 agents, which build efficacy over time) and that if the first biologic does not achieve the desired response, switching mechanism or agent is a standard and effective strategy.

Limitations and Evolving Questions

Despite the wealth of head-to-head data, several clinically relevant comparisons remain unaddressed. There are no large direct trials comparing IL-23 inhibitors to each other (risankizumab versus guselkumab), and the optimal approach when a patient fails one IL-23 agent — switch within class or change mechanism — is based on clinical judgment rather than randomized evidence. Whether the higher candidiasis rate with bimekizumab represents a clinically significant safety concern or a manageable adverse effect that is outweighed by its superior clearance rates is a question that longer-term real-world data will help resolve. And the cost of biologic therapy remains a significant barrier that prevents many eligible patients from accessing these treatments at all.

References

1. Secukinumab in plaque psoriasis - results of two phase 3 trials (ERASURE and FIXTURE)
2. Phase 3 Trials of Ixekizumab in Moderate-to-Severe Plaque Psoriasis (UNCOVER-1, -2, -3)
3. Bimekizumab efficacy and safety in moderate to severe plaque psoriasis (BE READY)
4. Bimekizumab efficacy and safety in moderate to severe plaque psoriasis (BE READY)
5. Efficacy and safety of guselkumab compared with adalimumab for continuous treatment of moderate to severe psoriasis (VOYAGE 1)
6. Efficacy and safety of risankizumab in moderate-to-severe plaque psoriasis (UltIMMa-1 and UltIMMa-2)
7. Tildrakizumab versus placebo or etanercept for chronic plaque psoriasis (reSURFACE 1 and reSURFACE 2)
8. Efficacy and safety of risankizumab vs. secukinumab in patients with moderate-to-severe plaque psoriasis (IMMerge)
9. Guselkumab versus secukinumab for the treatment of moderate-to-severe psoriasis (ECLIPSE)
10. Bimekizumab versus Secukinumab in Plaque Psoriasis (BE RADIANT)
11. Bimekizumab versus ustekinumab for the treatment of moderate to severe plaque psoriasis (BE VIVID)