Drug Monograph
Secukinumab (Cosentyx)
secukinumab — fully human anti-interleukin-17A monoclonal antibody (IgG1κ)
Pharmacokinetic Profile
Half-Life
22–31 days (mean ~27 days)
Metabolism
Intracellular catabolism (no CYP involvement)
Protein Binding
Not applicable (IgG1 antibody)
Bioavailability
~73% (SC); range 55–85% across indications
Volume of Distribution
~7–8 L (central 3.6 L + peripheral 2.9 L)
Clinical Information
Drug Class
IL-17A Inhibitor (Human IgG1κ mAb)
Available Doses
SC: 75 mg, 150 mg, 300 mg; IV: 125 mg/5 mL vial
Route
Subcutaneous; IV (PsA, AS, nr-axSpA only)
Renal Adjustment
Not studied (not expected to affect mAb PK)
Hepatic Adjustment
Not studied (not expected to affect mAb PK)
Pregnancy
Use only if benefit justifies risk (no animal teratogenicity)
Lactation
Unknown excretion in human milk; weigh benefit-risk
Schedule
Prescription only (not scheduled)
Generic Available
No
Black Box Warning
No
Approved Indications & Off-Label Uses
| Indication | Approved Population | Therapy Type | Status |
|---|---|---|---|
| Moderate to severe plaque psoriasis | Patients ≥6 years; candidates for systemic therapy or phototherapy | Monotherapy | FDA Approved |
| Active psoriatic arthritis | Patients ≥2 years | Monotherapy or with methotrexate | FDA Approved |
| Active ankylosing spondylitis | Adults | Monotherapy | FDA Approved |
| Active non-radiographic axial spondyloarthritis | Adults with objective signs of inflammation | Monotherapy | FDA Approved |
| Active enthesitis-related arthritis | Pediatric patients ≥4 years | Monotherapy | FDA Approved |
| Moderate to severe hidradenitis suppurativa | Adults | Monotherapy | FDA Approved |
Secukinumab was the first IL-17A inhibitor approved by the FDA (January 2015). Unlike JAK inhibitors, secukinumab does not carry a boxed warning and can be used as a first-line biologic in most of its approved indications without requiring prior TNF inhibitor failure. In PsA, it can be used with or without methotrexate. An IV formulation was approved in October 2023 for PsA, AS, and nr-axSpA.
Off-Label Uses
Reactive arthritis: Case series and small open-label studies support use. Evidence quality: Low.
Behcet’s disease (mucocutaneous): Case reports of benefit. Evidence quality: Very low.
Generalized pustular psoriasis: Approved in some countries; data from Phase III trials available. Evidence quality: Moderate.
Dosing by Clinical Scenario
Subcutaneous Dosing — Primary Indications
| Clinical Scenario | Starting Dose | Maintenance Dose | Maximum Dose | Notes |
|---|---|---|---|---|
| Plaque psoriasis — adults | 300 mg SC at weeks 0, 1, 2, 3, 4 | 300 mg SC every 4 weeks | 300 mg q4w | 150 mg may be acceptable for some patients Each 300 mg dose can be given as 1×300 mg or 2×150 mg injections |
| Plaque psoriasis — pediatric (≥6 years, ≥50 kg) | 150 mg SC at weeks 0, 1, 2, 3, 4 | 150 mg SC every 4 weeks | 150 mg q4w | Weight-based: <50 kg = 75 mg |
| Psoriatic arthritis — with loading dose | 150 mg SC at weeks 0, 1, 2, 3, 4 | 150 mg SC every 4 weeks | 300 mg q4w | Increase to 300 mg if persistent active disease; use PsO dosing if coexistent moderate-severe PsO May be given with or without methotrexate |
| Psoriatic arthritis — without loading dose | 150 mg SC every 4 weeks | 150 mg SC every 4 weeks | 300 mg q4w | Consider 300 mg for inadequate response |
| Ankylosing spondylitis — with loading dose | 150 mg SC at weeks 0, 1, 2, 3, 4 | 150 mg SC every 4 weeks | 300 mg q4w | Increase to 300 mg if persistent active AS |
| Ankylosing spondylitis — without loading dose | 150 mg SC every 4 weeks | 150 mg SC every 4 weeks | 300 mg q4w | Loading dose is optional |
| Non-radiographic axial spondyloarthritis | 150 mg SC ± loading | 150 mg SC every 4 weeks | 150 mg q4w | With or without loading; loading = weeks 0, 1, 2, 3, 4 |
| Hidradenitis suppurativa — adults | 300 mg SC at weeks 0, 1, 2, 3, 4 | 300 mg SC every 4 weeks | 300 mg q2w | If inadequate response, increase to 300 mg every 2 weeks FDA approved for HS in 2023 |
| Enthesitis-related arthritis (≥4 years) | Weight-based: ≥50 kg=150 mg; ≥15 to <50 kg=75 mg | Same dose every 4 weeks | 150 mg q4w | Loading at weeks 0, 1, 2, 3, 4 |
Intravenous Dosing (PsA, AS, nr-axSpA Only — Adults)
| Clinical Scenario | Starting Dose | Maintenance Dose | Maximum Dose | Notes |
|---|---|---|---|---|
| PsA / AS / nr-axSpA — IV with loading | 6 mg/kg IV at Week 0 | 1.75 mg/kg IV every 4 weeks | 300 mg per infusion (maintenance) | Infuse over 30 minutes; approved Oct 2023 Use in-line 0.2 μm filter; dilute in 0.9% NaCl |
| PsA / AS / nr-axSpA — IV without loading | 1.75 mg/kg IV every 4 weeks | 1.75 mg/kg IV every 4 weeks | 300 mg per infusion | No loading dose option available |
Clinical Pearl — Loading Dose Strategy
The weekly loading dose at weeks 0–4 rapidly builds serum concentrations toward the therapeutic threshold (~20 μg/mL trough at steady state). Without loading, steady-state is not reached until approximately week 24. For PsA and AS, the loading dose is optional, but most clinicians use it to achieve faster symptom relief, particularly in patients with high disease activity. For plaque psoriasis and HS, the loading dose is always recommended.
Pharmacology & Mechanism of Action
Mechanism of Action
Secukinumab is a fully human IgG1κ monoclonal antibody that selectively binds to and neutralises interleukin-17A (IL-17A), a pro-inflammatory cytokine central to the pathogenesis of psoriatic disease, spondyloarthritis, and other IL-17-driven inflammatory conditions. IL-17A is produced predominantly by Th17 cells, γδ T cells, and innate lymphoid cells, and drives keratinocyte proliferation, neutrophil recruitment, and osteoclastogenesis in the joints and entheses. By blocking IL-17A binding to its receptor (IL-17RA/IL-17RC heterodimer), secukinumab suppresses downstream production of chemokines (CXCL1, CXCL8), antimicrobial peptides, and matrix metalloproteinases, thereby reducing the inflammatory cascade in skin, joints, and axial skeleton. Secukinumab does not bind IL-17F, IL-17B, IL-17C, IL-17D, or IL-17E.
ADME Profile
| Parameter | Value | Clinical Implication |
|---|---|---|
| Absorption | SC: Tmax ~5–6 days; bioavailability ~73% (range 55–85% across indications); steady state by week 24 with loading, with ~2-fold accumulation | Loading doses at weeks 0–4 rapidly build therapeutic levels; without loading, steady state is delayed to ~24 weeks |
| Distribution | Vd ~7–8 L total (central 3.6 L, peripheral 2.9 L); skin interstitial fluid concentrations reach 27–40% of serum levels | Vd close to blood volume — confirms limited tissue distribution typical of IgG1 antibodies; adequate skin penetration for psoriatic plaques |
| Metabolism | Intracellular catabolism to amino acids and small peptides; no CYP enzyme involvement; no active metabolites | Extremely low drug interaction potential — no CYP-mediated metabolism or transport interactions expected |
| Elimination | CL ~0.19 L/day; t½ 22–31 days (mean ~27 days); clearance and Vd increase with body weight | Monthly dosing interval well-supported by the long half-life; heavier patients may have lower trough concentrations |
Side Effects & Adverse Reactions
Data below are primarily from the pooled Phase III placebo-controlled psoriasis trials (PsO1–PsO4; COSENTYX 300 mg N=691, 150 mg N=692, placebo N=694) through 12 weeks (FDA PI). Long-term data from the open-label extension represent up to 3,582 subject-years of exposure.
≥10%
Very Common
| Adverse Effect | Incidence | Clinical Note |
|---|---|---|
| Nasopharyngitis | 11.4% (300 mg) | Most common adverse reaction; mild, self-limiting (vs 8.6% placebo) |
1–10%
Common
| Adverse Effect | Incidence | Clinical Note |
|---|---|---|
| Diarrhoea | 4.1% (300 mg) | Dose-related; generally mild and transient (vs 1.4% placebo) |
| Upper respiratory tract infection | 2.5% (300 mg) | Includes sinusitis, pharyngitis (vs 0.7% placebo) |
| Rhinitis | 1.4% | Mild; vs 0.7% placebo |
| Oral herpes | 1.3% (300 mg) | Dose-related pattern; herpes viral infections increase with higher serum concentrations (vs 0.3% placebo) |
| Mucocutaneous candida infections | 1.2% (300 mg) | Reflects the role of IL-17A in mucosal antifungal defence; includes oral and oesophageal candidiasis (vs 0.3% placebo). Most were mild-moderate and resolved with standard antifungal therapy |
| Pharyngitis | 1.2% (300 mg) | Mild (vs 0% placebo) |
| Urticaria | 1.2% (150 mg) | Hypersensitivity-related; usually mild |
| Rhinorrhoea | 1.2% (300 mg) | Mild (vs 0.1% placebo) |
Serious
Serious Adverse Effects (Regardless of Frequency)
| Adverse Effect | Estimated Frequency | Typical Onset | Required Action |
|---|---|---|---|
| Serious infections | 1.2% over 52 weeks (0.015/subject-year); 1.4/100 PY long-term | Any time during treatment | Discontinue until infection resolves; monitor closely; most common serious infections were cellulitis and pneumonia |
| Inflammatory bowel disease (new onset or exacerbation) | Uncommon (~0.1–0.2/100 PY) | Variable; weeks to months | Exercise caution in patients with IBD history; monitor for GI symptoms; discontinue if serious IBD develops; secukinumab worsened disease in an exploratory Crohn’s disease trial |
| Neutropenia (ANC <1.0 ×109/L) | ~1% long-term (0.3/100 PY) | Early treatment course | Most cases transient and reversible; no associated serious infections in the majority; monitor if clinically indicated |
| Anaphylaxis / angioedema | Rare | Any injection/infusion | Discontinue permanently; initiate emergency therapy; contraindicated in known hypersensitivity to secukinumab |
| Severe eczematous eruptions (postmarketing) | Rare (postmarketing reports) | Days to months after first dose | May need to discontinue; some patients were managed while continuing therapy; includes atopic dermatitis-like and dyshidrotic eczema eruptions |
| Hepatitis B reactivation | Rare (postmarketing) | Variable | Screen for HBV before initiation; consult hepatology if reactivation occurs; not recommended in active viral hepatitis |
Discontinuation
Discontinuation Rates
Adults (PsO — open-label extension)
4.5–5.4/100 PY TEAE leading to discontinuation
Top reasons: Infections, IBD, hypersensitivity reactions
Real-World PsA (GISEA Registry)
2.2% AE-related discontinuation
Note: Includes paradoxical psoriasis, GI discomfort, and Crohn’s disease as reported reasons
| Reason for Discontinuation | Incidence | Context |
|---|---|---|
| Infections | Most common | Serious infections (cellulitis, pneumonia) were the leading cause |
| Inflammatory bowel disease | Uncommon | Both new-onset and exacerbation of pre-existing IBD have led to discontinuation |
| Hypersensitivity | Rare | Urticaria, anaphylaxis, angioedema |
Managing Candida Infections
IL-17A plays a critical role in mucosal defence against Candida species. Patients on secukinumab have a higher rate of mucocutaneous candidiasis (oral thrush, oesophageal candidiasis) than those on placebo, and the rate increases with higher serum drug concentrations. Most cases are mild to moderate and respond to standard antifungal treatment without requiring discontinuation. Counsel patients to report persistent oral white patches, dysphagia, or vaginal candidiasis.
Drug Interactions
Secukinumab is a monoclonal antibody eliminated via intracellular catabolism. It does not interact with CYP enzymes or drug transporters and has minimal pharmacokinetic drug interaction potential. The main interactions are pharmacodynamic — relating to additive immunosuppression or impaired vaccine responses.
MajorLive Vaccines (MMR, varicella, oral polio, BCG, yellow fever)
MechanismIL-17A blockade impairs immune response to live vaccine antigens
EffectRisk of vaccine-strain infection; potential for diminished immunogenicity
ManagementAvoid live vaccines during treatment. Complete all live vaccinations before initiating secukinumab. Inactivated and recombinant vaccines may be given
FDA PIModerateOther Immunosuppressants / Biologics
MechanismAdditive immunosuppression through complementary immune pathways
EffectIncreased infection risk without established additional benefit
ManagementCombination with other biologics not studied and not recommended. Methotrexate may be used concurrently in PsA. Allow adequate washout when switching between biologics
FDA PI / Clinical PracticeModerateCYP450 Substrates with Narrow Therapeutic Index (warfarin, ciclosporin, theophylline)
MechanismChronic inflammation suppresses CYP activity; IL-17 inhibition may normalise CYP expression (theoretical)
EffectPotential for decreased levels of narrow-TI drugs as inflammation resolves (class effect of cytokine inhibitors)
ManagementConsider monitoring narrow-TI drugs when initiating or discontinuing secukinumab, especially warfarin (monitor INR)
FDA PI / Pharmacological TheoryMinorMethotrexate
MechanismNo pharmacokinetic interaction; complementary mechanisms
EffectCombination studied in FUTURE trials for PsA; no dose adjustment needed
ManagementAcceptable and studied combination for PsA; standard MTX monitoring applies
FUTURE 1 & 2 TrialsMonitoring Parameters
- TB ScreeningBaseline
RoutineEvaluate for latent and active TB before initiating. Do not start in active TB; treat latent TB before initiation. Monitor for TB signs/symptoms during treatment. Postmarketing cases of active TB in patients with latent TB history have been reported. - Hepatitis B ScreeningBaseline
RoutineScreen HBsAg, anti-HBc, anti-HBs. HBV reactivation reported in postmarketing setting. Not recommended in active viral hepatitis. Consult hepatology for HBsAg-positive patients. - Signs of InfectionEvery visit
Trigger-basedMonitor for fever, cough, dyspnoea, skin infections, oral thrush. Candida infections are a known risk. Discontinue secukinumab for serious infections until resolved. - IBD SymptomsEvery visit
Trigger-basedAsk about new or worsening abdominal pain, diarrhoea, bloody stools. Cases of Crohn’s disease and ulcerative colitis (exacerbation and new onset) occurred in clinical trials. Exercise particular caution in patients with pre-existing IBD. - Skin ExaminationPeriodic
Trigger-basedMonitor for eczematous eruptions (atopic dermatitis-like, dyshidrotic eczema, erythroderma), which have been reported in postmarketing. Some cases required hospitalization. Also evaluate injection site reactions. - ImmunisationsBaseline
RoutineComplete age-appropriate vaccinations before starting. Avoid live vaccines during treatment. Inactivated vaccines (including influenza, COVID-19) can be given. Consider Shingrix completion within the first year.
Contraindications & Cautions
Absolute Contraindications
- Known serious hypersensitivity to secukinumab or any excipient — anaphylaxis and angioedema have been reported
- Active tuberculosis infection — treat latent TB before initiation
Relative Contraindications (Specialist Input Recommended)
- Active inflammatory bowel disease — secukinumab worsened Crohn’s disease in an exploratory trial; new-onset IBD occurred in clinical trials; exercise extreme caution and consider alternative agents
- Active serious infection — do not initiate until infection is controlled
- Active viral hepatitis (HBV or HCV) — not recommended; HBV reactivation reported postmarketing
Use with Caution
- Chronic or recurrent infections — higher infection rate observed versus placebo; monitor closely
- Latex sensitivity — removable caps of Sensoready pen and certain prefilled syringes contain natural rubber latex
- Pregnancy — limited human data; no animal teratogenicity observed at up to 30× MRHD; use only if benefit justifies risk
- Concomitant immunosuppressive biologics — combination with other biologics not studied and not recommended
FDA Safety Advisory — Inflammatory Bowel Disease
IBD Exacerbation and New-Onset IBD
Exacerbations of Crohn’s disease and ulcerative colitis, including new-onset cases, occurred during clinical trials with secukinumab across all approved indications. An exploratory trial in active Crohn’s disease showed trends toward worsened disease activity with secukinumab compared to placebo. In the HS programme, IBD incidence was higher at the 300 mg q2w dose. Exercise caution when prescribing secukinumab to patients with IBD and monitor for GI symptoms throughout treatment.
Patient Counselling
Purpose of Therapy
Secukinumab is a biologic medicine that targets a specific protein called IL-17A, which drives the inflammation responsible for skin plaques, joint pain, and spinal stiffness. By blocking IL-17A, it reduces inflammation in the skin, joints, and spine. It is given as an injection under the skin (or occasionally as an IV infusion) and works over several weeks to improve symptoms.
How to Take
Secukinumab is injected subcutaneously (under the skin) in the thigh, abdomen, or upper arm. The first five doses are given weekly (at weeks 0, 1, 2, 3, and 4) to build up the medicine quickly, followed by one injection every four weeks. Patients or caregivers can learn to self-inject at home after proper training. Rotate injection sites and avoid areas of tender, bruised, or psoriatic skin. Allow pens/syringes to reach room temperature before injection (15–45 minutes depending on device).
Infection Risk
Tell patientThis medicine can lower your ability to fight certain infections. Good hand hygiene, avoiding people who are unwell, and staying up to date with vaccinations (before starting treatment) are all important. Yeast infections (oral thrush, vaginal candidiasis) may be more common because the protein this medicine blocks also helps defend against yeast.
Call prescriberContact your doctor if you develop fever, persistent cough, painful or red skin areas, white patches in the mouth that do not resolve, or any signs of a serious infection.
Bowel Symptoms
Tell patientIn rare cases, this medicine has been associated with new or worsening inflammatory bowel disease (such as Crohn’s disease). It is important to report any new persistent abdominal pain, diarrhoea, or blood in the stool.
Call prescriberSeek prompt medical attention for persistent or severe abdominal pain, bloody diarrhoea, or unexplained weight loss.
Allergic Reactions
Tell patientSerious allergic reactions (including swelling of the face, lips, or tongue, difficulty breathing, and widespread rash) have been reported rarely. The Sensoready pen and some prefilled syringe caps contain natural rubber latex — inform your prescriber if you have a latex allergy.
Call prescriberSeek emergency care immediately for any signs of a severe allergic reaction after injection.
Storage & Self-Injection
Tell patientStore secukinumab in the refrigerator (2–8°C). Do not freeze or shake. Allow the pen or syringe to reach room temperature before injection. Inspect the solution — it should be clear to slightly opalescent and colourless to slightly yellow. Do not use if discoloured or containing particles.
Call prescriberIf you are unsure about injection technique or notice persistent redness, swelling, or pain at the injection site that does not improve.
Skin Changes
Tell patientRarely, patients have developed new eczema-like skin eruptions while taking secukinumab. This is different from your psoriasis and may appear as itchy, weeping, or red patches, sometimes on the hands or feet.
Call prescriberReport any new rash or skin changes that look different from your usual psoriasis or skin condition.
Sources
Regulatory (PI / SmPC)
- COSENTYX (secukinumab) [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals Corp.; Revised 08/2025. FDA Label (PDF)Primary regulatory source for all dosing, indications, adverse reactions, and warnings. Includes HS indication and updated IBD/hypersensitivity warnings.
- European Medicines Agency. Cosentyx (secukinumab): EPAR — Product information. EMA Product PageEU regulatory perspective including SmPC; provides complementary pregnancy/lactation guidance.
Key Clinical Trials
- Langley RG, Elewski BE, Lebwohl M, et al. Secukinumab in plaque psoriasis — results of two phase 3 trials. N Engl J Med. 2014;371(4):326-338. doi:10.1056/NEJMoa1314258ERASURE and FIXTURE trials establishing secukinumab 300 mg efficacy in moderate-to-severe plaque psoriasis; source for primary adverse reaction data.
- Mease PJ, McInnes IB, Kirkham B, et al. Secukinumab inhibition of interleukin-17A in patients with psoriatic arthritis. N Engl J Med. 2015;373(14):1329-1339. doi:10.1056/NEJMoa1412679FUTURE 1 trial demonstrating significant ACR20 response in PsA with secukinumab, including resolution of dactylitis and enthesitis.
- McInnes IB, Mease PJ, Kirkham B, et al. Secukinumab, a human anti-interleukin-17A monoclonal antibody, in patients with psoriatic arthritis (FUTURE 2). Lancet. 2015;386(9999):1137-1146. doi:10.1016/S0140-6736(15)61134-5FUTURE 2 trial with SC-only loading; demonstrated sustained ACR20/50/70 responses through 2 years.
- Baeten D, Sieper J, Braun J, et al. Secukinumab, an interleukin-17A inhibitor, in ankylosing spondylitis. N Engl J Med. 2015;373(26):2534-2548. doi:10.1056/NEJMoa1505066MEASURE 1 and MEASURE 2 trials establishing secukinumab efficacy in AS; ASAS20/40 endpoints significantly improved versus placebo.
- Deodhar A, Blanco R, Engström-Laurent A, et al. Secukinumab improves signs and symptoms of non-radiographic axial spondyloarthritis: primary results of a randomized controlled phase III study. Arthritis Rheumatol. 2021;73(1):110-120. doi:10.1002/art.41477Phase III trial establishing secukinumab 150 mg efficacy in nr-axSpA with significant ASAS40 improvement versus placebo at week 16.
Guidelines
- Gossec L, Kerschbaumer A, Ferreira RJO, et al. EULAR recommendations for the management of psoriatic arthritis with pharmacological therapies: 2023 update. Ann Rheum Dis. 2024;83(6):706-719. doi:10.1136/ard-2024-225531Most recent EULAR PsA recommendations; positions IL-17 inhibitors as first-line biologic options alongside TNF inhibitors, with specific guidance based on skin involvement and extra-musculoskeletal manifestations.
- Ramiro S, Nikiphorou E, Sepriano A, et al. ASAS-EULAR recommendations for the management of axial spondyloarthritis: 2022 update. Ann Rheum Dis. 2023;82(1):19-34. doi:10.1136/ard-2022-223296ASAS-EULAR 2022 update recommends IL-17 inhibitors as first-line biologics for axial SpA; addresses the position of secukinumab alongside TNF inhibitors.
Mechanistic / Basic Science
- Gaffen SL, Jain R, Garg AV, Cua DJ. The IL-23–IL-17 immune axis: from mechanisms to therapeutic testing. Nat Rev Immunol. 2014;14(9):585-600. doi:10.1038/nri3707Foundational review of the IL-23/IL-17 axis explaining why IL-17A blockade is effective in psoriatic disease and spondyloarthritis.
Pharmacokinetics / Special Populations
- Bruin G, Loesche C, Nyirady J, Sander O. Population pharmacokinetic modeling of secukinumab in patients with moderate to severe psoriasis. J Clin Pharmacol. 2017;57(7):876-885. doi:10.1002/jcph.875Definitive population PK model for secukinumab; source for clearance (0.19 L/day), Vd, bioavailability (73%), and body weight effects.
- Deodhar A, Mease PJ, McInnes IB, et al. Long-term safety of secukinumab in patients with moderate-to-severe plaque psoriasis, psoriatic arthritis, and ankylosing spondylitis: integrated pooled clinical trial and post-marketing surveillance data. Arthritis Res Ther. 2019;21(1):111. doi:10.1186/s13075-019-1882-2Integrated long-term safety analysis pooling clinical trial and postmarketing data across PsO, PsA, and AS; provides exposure-adjusted serious infection and IBD rates.
- Kolbinger F, Di Padova F, Deodhar A, et al. Secukinumab for the treatment of psoriasis, psoriatic arthritis, and axial spondyloarthritis: physical and pharmacological properties underlie the observed clinical efficacy and safety. Pharmacol Ther. 2022;229:107925. doi:10.1016/j.pharmthera.2021.107925Comprehensive review linking PK properties (half-life, tissue distribution, therapeutic index) to clinical outcomes; source for skin interstitial fluid concentration data.