IL-17 and IL-23 biologics in FAERS: 400,283 adverse-event reports by the numbers

The FDA Adverse Event Reporting System (FAERS) holds 400,283 individual safety reports that name at least one of the eight marketed IL-17, IL-23, and IL-12/23 biologics — secukinumab (Cosentyx), ustekinumab (Stelara), risankizumab (Skyrizi), ixekizumab (Taltz), guselkumab (Tremfya), bimekizumab (Bimzelx), tildrakizumab (Ilumya), and brodalumab (Siliq) — in any role, filed between 2009, when ustekinumab launched, and early 2026. Secukinumab leads the class with 148,500 reports (37.1 percent), ahead of ustekinumab at 89,869 (22.5 percent) and a fast-rising risankizumab at 78,647 (19.6 percent). A class-level 43.3 percent of reports — 173,138 — carry an FDA seriousness flag, and 9,097 reports (2.27 percent) record a fatal outcome. The reaction list is dominated by lack-of-efficacy and psoriasis terms — "drug ineffective" at 43,672 and "psoriasis" at 39,230 — but the family that defines the class sits lower in the raw count: 12,472 reports across the inflammatory-bowel-disease family, the postmarketing footprint of the IL-17 paradox that splits this class in half.

This article is a class-level descriptive read of IL-17, IL-23, and IL-12/23 biologic reporting in FAERS, written for pharmacovigilance, medical-affairs, market-access, and dermatology/rheumatology/gastroenterology teams who encounter these safety numbers in sequencing decisions, prior-authorization rationale, and the IL-17-versus-IL-23 formulary debate. Every figure here is computed from the public openFDA FAERS extract (20,328,575 total reports, export dated 2026-06-08). It is not a disproportionality signal analysis, it is not a safety claim, and it is not incidence data. FAERS is a spontaneous-reporting system: it captures what was reported, never what was caused, and it has no exposure denominator. These biologics are now among the highest-volume specialty dermatology and immunology agents in the world, so the reporting volume here is a small, skewed slice of real-world exposure. Those caveats shape every number below, and the small-denominator artifacts at the tail of the per-drug table — brodalumab and tildrakizumab — are spelled out explicitly. For the class-wide FAERS methodology and the database aggregate picture, see the companion analysis of 20 million FAERS reports; for adjacent class cuts, see TNF inhibitors and JAK inhibitors in FAERS. For the access picture, see the IL-23 inhibitor access landscape, the Cosentyx coverage guide, the Skyrizi coverage guide, and the Stelara biosimilar comparison. This article stays on the eight marketed IL-17/IL-23/IL-12/23 biologics.

Methodology, in one paragraph

A report is counted for an agent when its generic or brand name appears anywhere in that report's drug list — as a suspect, concomitant, or interacting drug — using a case-insensitive substring match across the drug_substances and drug_brands fields. Because a single report can name several drugs, the per-substance totals sum to more than the 400,283 class-level (union, deduplicated) reports: roughly 22,000 reports name more than one agent in the class, typically a patient sequenced from a TNF blocker to an IL-17 or IL-23, or between IL-17 and IL-23 agents. A "serious" report is any report the FDA coded as serious. A report counts toward death when the seriousness field carries a death flag; the resolved-Fatal-outcome field sits slightly lower (8,259 reports). Reactions are coded to MedDRA Preferred Terms; reaction counts are case-normalized to avoid splitting the same concept across "Injection site pain" and "INJECTION SITE PAIN," and the caret-encoded apostrophe in "Crohn^s disease" is normalized to "Crohn's disease." The adverse-event families aggregate related Preferred Terms (for example, "inflammatory bowel disease" combines Crohn's disease, ulcerative colitis, colitis, and inflammatory bowel disease terms), and a report contributes once to a family if any term in the family appears. The "any role" counts reported here are intentionally inclusive, so they will exceed suspect-only or differently normalized counts cited elsewhere for the same agent.

The reporting-volume picture, by drug

Three patterns matter for access and medical-affairs teams. First, volume tracks market tenure and dermatology penetration, not intrinsic risk: secukinumab leads because Cosentyx was first-in-class among the IL-17s (2015) and built the largest dermatology franchise, and ustekinumab's share reflects its 2009 launch and its long run as the dominant IL-12/23 before the IL-23-specific agents arrived. Second, risankizumab's serious share (63.6 percent) is the highest among the high-volume agents and reflects its expansion beyond plaque psoriasis into Crohn's disease (2022) and ulcerative colitis (2024) — IBD indications that pull a sicker, hospitalized reporting population into its mix, the opposite of the outpatient-dermatology skew that keeps ixekizumab (20.6 percent) and guselkumab (25.5 percent) low. Third, the two tail agents are small-denominator artifacts that must not be read as safety differentials: brodalumab's 88.6 percent serious share and 7.07 percent death-flag rate sit on just 2,192 reports — a residual, restricted population carrying a Boxed Warning for suicidal ideation and behavior and a REMS — and tildrakizumab's 9.08 percent death-flag rate sits on 2,423 reports. Both are statistical noise at this scale, not evidence that either agent is more dangerous than secukinumab. Quoting either tail percentage without that caveat is quoting a small-sample artifact.

The class-level outcome profile

A report can carry more than one outcome, so these shares sum to more than 100 percent. The dominant "unknown outcome" share — 69.9 percent, among the highest in this series — reflects a consumer-dominated reporting mix in which follow-up is rarely updated. The Fatal outcome count (8,259) sits below the death-flag measure (9,097) because not every death-flagged report carries a resolved Fatal outcome field. At the report level, 54,411 reports (13.6 percent) flag a hospitalization, 3,741 (0.9 percent) flag a life-threatening event, and 2,715 flag a disabling outcome. None of these percentages is incidence — the denominator is reports, not exposed patients.

The inflammatory-bowel-disease signal, and the paradox that splits the class

Stripping out the non-specific terms (drug ineffective, pain, fatigue, headache) that dominate the raw reaction list, the label-relevant adverse-event families that define the IL-17/IL-23 profile leave a clear footprint:

The IBD family is the family that defines this class — and it defines it in opposite directions for the two halves of the mechanism. The IL-17 inhibitors (secukinumab, ixekizumab, brodalumab, bimekizumab) carry label warnings for inflammatory bowel disease because blockade of IL-17A can exacerbate or unmask Crohn's disease and ulcerative colitis. A phase II trial of secukinumab in Crohn's disease was terminated for worsening disease, the Cosentyx label recommends caution and monitoring in patients with active Crohn's, and the EMA added an inflammatory-intestinal-disease term to the secukinumab summary of product characteristics in 2018–2019. Published FAERS disproportionality work has reported reporting-odds-ratio signals for IBD with secukinumab (Crohn's ROR 1.57; ulcerative colitis 2.08; IBD 4.0) and ixekizumab (Crohn's 1.45; UC 3.58; IBD 5.42) — the 12,472-report IBD family here is the descriptive volume behind those signals, with Crohn's disease coded as a reaction term on 7,687 reports across the class.

The IL-23 inhibitors move in exactly the opposite direction. Risankizumab (Skyrizi) was approved for moderately to severely active Crohn's disease in June 2022 and for ulcerative colitis in June 2024 — making it the first IL-23-specific inhibitor approved for both — and ustekinumab (Stelara, IL-12/23) is likewise approved for Crohn's and UC. So the same FAERS database records IL-23 agents treating the very disease that IL-17 agents worsened. That contrast is now the single most-cited clinical point in IL-17-versus-IL-23 sequencing: for a psoriasis patient with comorbid or at-risk IBD, the IL-23 agents are the preferred class and the IL-17 agents are relatively contraindicated in active Crohn's disease. The raw IBD reporting counts include both phenomena — Crohn's disease appears in reports for risankizumab as an indication being treated and in reports for secukinumab as an adverse event — so the family total is not a clean signal count for either direction, and the disproportionality literature, not the raw volumes, established the IL-17 signal.

The infection family (58,009 reports) carries the candidiasis signal unique to IL-17 blockade: IL-17 is central to mucocutaneous defense against Candida, so mucocutaneous candidiasis is the characteristic infection of the IL-17 class and appears in the Cosentyx, Taltz, and Bimzelx warnings and precautions. The eczematous-eruption family (1,702 reports) captures the severe eczematous and atopic-dermatitis-like eruptions, including erythroderma, that the secukinumab label flags in postmarketing reports.

Who is reporting

Consumers file 56 percent of the class's reports — a share that reflects the self-administered subcutaneous pen and syringe presentations that dominate Cosentyx, Taltz, Tremfya, Skyrizi, and Bimzelx and the direct-to-consumer marketing environment around psoriasis biologics. The physician share (13.8 percent) is lower than the TNF-blocker class because these agents are concentrated in outpatient dermatology and rheumatology rather than inpatient gastroenterology. The consumer-dominated mix is one reason the serious share (43.3 percent) sits below the TNF class and the "unknown outcome" share is so high.

The indication mix, and the IL-23 IBD expansion

The reaction list reads as a dermatology and psoriatic-disease indication map: psoriasis (39,230 reports as a coded reaction term), psoriatic arthropathy (9,440), and the pruritus and arthralgia cluster that surrounds them. The indication expansion that matters most for the class is the IL-23 move into inflammatory bowel disease — risankizumab's Crohn's (2022) and UC (2024) approvals, and ustekinumab's long-standing IBD indications — which is reshaping both the reporting population (pulling hospitalized IBD cases into risankizumab's mix) and the sequencing logic (IL-23 over IL-17 for IBD-at-risk patients). The COVID-19 term (8,609 reports) reflects the 2020–2022 pandemic window in which immunomodulated patients were a reporting focus.

The year-over-year accumulation curve

Two inflection points are visible. The 2015 jump (7,905 reports, from 1,656 the year before) tracks the secukinumab launch and the beginning of the IL-17 era in dermatology; the steady climb through 2018–2019 reflects the ixekizumab, guselumab, and tildrakizumab launches and risankizumab's 2019 entry. The 2022 step-up (50,946) coincides with risankizumab's Crohn's approval and the full expansion of the IL-23 franchise into IBD, and the 2025 peak (54,221) reflects continued IL-23 uptake and the bimekizumab expansion. Unlike the TNF class, IL-17/IL-23 reporting is still climbing, not declining, because these agents are earlier in their market lifecycle and still gaining formulary share.

What the labels actually say, and how they reach the formulary

The IL-17 and IL-23 labels share a warnings-and-precautions framework — serious infections, tuberculosis evaluation, and hypersensitivity — but diverge sharply on inflammatory bowel disease and on the candidiasis signal. The IL-17 inhibitors (Cosentyx, Taltz, Bimzelx, Siliq) carry the IBD-exacerbation warning and the mucocutaneous-candidiasis warning; brodalumab additionally carries a Boxed Warning for suicidal ideation and behavior with a REMS, which is the single largest access constraint on that agent and the reason its reporting base is so small. The IL-23 inhibitors (Skyrizi, Tremfya, Ilumya) and ustekinumab carry the cleaner serious-infection and hypersensitivity framework without the IBD-exacerbation warning, and risankizumab and ustekinumab are actively approved to treat IBD. The access consequence is the IL-17-versus-IL-23 sequencing logic: for IBD-at-risk psoriasis patients, IL-23 is preferred; for patients where IL-23 has failed or rapid skin clearance is the priority, IL-17 remains first-line, with IBD screening built into the PA criteria. Biosimilar entry is now reaching the IL-12/23 anchor: Stelara (ustekinumab) biosimilars are now FDA-approved and several carry interchangeability, which is reshaping the cost basis of the class.

How to read these numbers (and how not to)

• Volume is market tenure, not risk. Secukinumab's 148,500 reports reflect a 2015 launch and the largest dermatology franchise in the class; risankizumab's 78,647 reflect a 2019 launch and a still-expanding indication set. Rank reports per patient-year of exposure — which FAERS cannot compute — and the ordering changes.
• The IBD family cuts both ways. IL-17 agents worsen IBD; IL-23 agents treat it. The raw IBD count blends both, so it is not a clean signal for either direction.
• The tail agents are small-sample artifacts. Brodalumab's 88.6 percent serious share and tildrakizumab's 9.08 percent death-flag rate sit on roughly 2,000 reports each. Do not quote either as a safety differential.
• FAERS has no denominator. None of these numbers is an incidence rate, a relative risk, or a causal estimate. A 400,283-report class total says the surveillance system is watching this class; it does not say the class caused 400,283 events.

Sources

• US FDA, FDA Adverse Event Reporting System (FAERS) / openFDA drug adverse event data, public extract (20,328,575 reports, export dated 2026-06-08). Aggregates computed by PharmaDossier from the openFDA FAERS full extract. https://open.fda.gov/data/faers/
• US FDA, COSENTYX (secukinumab) Prescribing Information, including Warnings and Precautions for infections, inflammatory bowel disease, and hypersensitivity. https://www.rxlist.com/cosentyx-drug.htm
• Aetna, "Secukinumab (Cosentyx) Medical Clinical Policy Bulletin" — labeled warnings and precautions: serious infections, tuberculosis, inflammatory bowel disease, eczematous eruptions, hypersensitivity. https://www.aetna.com/cpb/medical/data/900_999/0905.html
• Napolitano M, et al., "A Review of the Safety of Interleukin-17A Inhibitor Secukinumab" (IBD comorbidity in psoriasis; secukinumab phase II Crohn's trial termination; postmarketing IBD/colitis signals). PMC9695424. https://pmc.ncbi.nlm.nih.gov/articles/PMC9695424
• Yang F, et al., "IL-17 inhibitor-associated inflammatory bowel disease" (FAERS reporting odds ratios for secukinumab, ixekizumab, brodalumab: Crohn's, ulcerative colitis, IBD). Frontiers in Pharmacology, 2023. https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2023.1124628/full
• AbbVie, "U.S. FDA Approves SKYRIZI (risankizumab-rzaa) for Ulcerative Colitis" (June 18, 2024) — first IL-23-specific inhibitor approved for both UC and Crohn's disease. https://news.abbvie.com/2024-06-18-U-S-FDA-Approves-SKYRIZI-R-risankizumab-rzaa-for-Ulcerative-Colitis,-Expanding-AbbVies-Portfolio-Across-Inflammatory-Bowel-Disease
• US FDA, Drugs.com Skyrizi (risankizumab) FDA approval history — plaque psoriasis (April 2019), psoriatic arthritis (2022), Crohn's disease (June 2022), ulcerative colitis (June 2024). https://www.drugs.com/history/skyrizi.html
• Venable / BiologicsHQ, "May 2025 Stelara and Humira Interchangeable Biosimilar Approvals" (ustekinumab biosimilar interchangeability). https://biologicshq.com/may-2025-stelara-and-humira-interchangeable-biosimilar-approvals
• US FDA, MedWatch adverse-event reporting program. https://www.fda.gov/safety/medwatch-fda-safety-information-and-adverse-event-reporting-program