secukinumab

**Mechanism:** Secukinumab binds IL-17A and prevents it from engaging the IL-17 receptor (IL-17RA/RC) on keratinocytes, synovial/entheseal cells, and other stromal cells. IL-17A is produced by Th17 cells, γδ T cells, ILC3s, and other cells, with IL-23 driving Th17 maintenance and expansion. Blocking IL-17A reduces downstream neutrophil recruitment and keratinocyte hyperproliferation (via IL-6, IL-8, CXCL1, GM-CSF, and antimicrobial peptides), which interrupts the psoriatic inflammatory cascade.

**Class and pathway:** It is an IL-17 inhibitor. Related drugs: ixekizumab (IL-17A), brodalumab (IL-17 receptor A antagonist), and bimekizumab (IL-17A and IL-17F). Compare these with IL-23 inhibitors (guselkumab, risankizumab, tildrakizumab), the IL-12/23 (p40) inhibitor ustekinumab, TNF-α inhibitors (adalimumab, etanercept, infliximab), and the PDE-4 inhibitor apremilast.

**Indications:** - Moderate-to-severe plaque psoriasis (candidates for systemic therapy or phototherapy) - Psoriatic arthritis - Ankylosing spondylitis and non-radiographic axial spondyloarthritis - Enthesitis-related arthritis (pediatric) - Hidradenitis suppurativa (approved in 2023)

**Administration:** Subcutaneous injection with loading doses (weekly for the first 5 weeks), then every 4 weeks. An IV formulation exists for some rheumatologic indications.

**Adverse effects (high-yield):** - **Mucocutaneous candidiasis** (oral, esophageal, vulvovaginal). IL-17 is critical for defense against Candida and extracellular bacteria at mucosal and epithelial surfaces. This links to the inborn errors of immunity: chronic mucocutaneous candidiasis (IL-17/IL-17R defects or AIRE mutations) and hyper-IgE syndrome (STAT3 mutation, so Th17 deficiency). - **Inflammatory bowel disease**: can exacerbate or newly cause Crohn disease and ulcerative colitis. Avoid or use caution in patients with active IBD. IL-17 appears to be protective for gut barrier integrity, and the IL-17 inhibitor trial in Crohn disease worsened disease. - Upper respiratory infections, nasopharyngitis, diarrhea. - Neutropenia (uncommon), hypersensitivity reactions including rare anaphylaxis, and a latex-sensitivity caution (some presentations' needle caps contain natural rubber latex). - Infection risk overall: screen for **latent TB** before starting (and treat if positive), although the TB reactivation risk appears lower than with TNF inhibitors. - Avoid live vaccines during therapy.

**Clinical pearls:** - It is a good option for psoriatic disease with axial or enthesitis involvement, where it is effective for both skin and joints. - It is not effective for Crohn disease, unlike IL-12/23 and IL-23 inhibitors (ustekinumab, risankizumab), which treat it. This is a classic board-style contrast. - It does not carry TNF-inhibitor class warnings for demyelinating disease or heart failure exacerbation, and it is not associated with the TNF-inhibitor risk of reactivating hepatitis B to the same degree, though screening is still prudent. - Brodalumab (not secukinumab) carries a boxed warning for suicidal ideation and behavior. - Mouse-derived (-omab), chimeric (-ximab), humanized (-zumab), and fully human (-umab) naming: secukinumab is "-umab," so fully human, which lowers immunogenicity.

**Naming:** "-kin-" denotes an interleukin target; "-u-" denotes a human source; "-mab" denotes a monoclonal antibody.