Secukinumab
IL 17A antibody for psoriasis and spondyloarthritides
Secukinumab is a fully human monoclonal IgG1 antibody that selectively neutralises interleukin 17A. Novartis launched the compound in 2015 under the brand name Cosentyx. Secukinumab was the first approved IL 17A inhibitor and has quickly established itself as one of the most important biologics in dermatology and rheumatology. It is approved for moderate to severe plaque psoriasis, for psoriatic arthritis, for ankylosing spondylitis and non radiographic axial spondyloarthritis, for hidradenitis suppurativa and, in paediatrics, for juvenile idiopathic arthritis and plaque psoriasis from the age of 6 years.
The clinical efficacy of secukinumab on skin and joints is well documented by numerous phase III trials (ERASURE, FIXTURE, MEASURE, FUTURE). In psoriasis, about 80 percent of treated patients achieve a 75 percent improvement in the PASI score after 12 weeks, and around 60 percent reach a 90 percent improvement. The safety data covering more than 10 years of clinical use are favourable, which makes secukinumab one of the most frequently prescribed biologics for inflammatory skin diseases.
Mechanism of Action
Interleukin 17A is a pro inflammatory cytokine produced primarily by T helper 17 cells but also by other immune cells. It plays a central role in the onset and maintenance of chronic inflammatory skin diseases and spondyloarthritides. Secukinumab binds with high affinity to IL 17A and prevents interaction with the IL 17 receptor complex.
This blockade interrupts downstream signalling pathways that activate pro inflammatory genes in keratinocytes, synoviocytes and entheses. The consequence is reduced chemokine release, reduced infiltration by inflammatory cells and reduced tissue remodelling. In the skin the plaques clear, in the joints the inflammatory activity decreases and in the spine inflammatory lesions recede.
The half life is about 27 days. After subcutaneous administration secukinumab is slowly absorbed and therapeutic plasma levels build up over the first weeks. As with other monoclonal antibodies, elimination takes place via proteolytic degradation. Dose adjustments in renal or hepatic impairment are not required.
Indications
- Moderate to severe plaque psoriasis in adults and children from 6 years who are candidates for systemic therapy
- Active psoriatic arthritis with inadequate response to conventional DMARDs or TNF inhibitors
- Active ankylosing spondylitis (Bechterew's disease) with inadequate response to conventional therapy
- Active non radiographic axial spondyloarthritis with objective signs of inflammation (elevated CRP, MRI findings)
- Active hidradenitis suppurativa in adults
- Juvenile idiopathic arthritis: enthesitis related arthritis and juvenile psoriatic arthritis in children from 6 years
Dosage and Administration
Plaque psoriasis in adults: 300 mg subcutaneously in weeks 0, 1, 2, 3 and 4, then every 4 weeks as maintenance dose. In patients with body weight of 90 kg or more and inadequate response to 300 mg every 4 weeks, dose escalation to 450 mg every 4 weeks is possible. Psoriatic arthritis: 150 mg in weeks 0, 1, 2, 3 and 4, then every 4 weeks. In case of previous TNF failure or concomitant moderate to severe plaque psoriasis 300 mg.
Ankylosing spondylitis and axial spondyloarthritis: 150 mg in weeks 0, 1, 2, 3 and 4, then every 4 weeks. Hidradenitis suppurativa: 300 mg in weeks 0, 1, 2, 3 and 4, then every 4 weeks, with the option to switch to every 2 weeks in case of inadequate response.
Paediatric patients: weight based dosing, plaque psoriasis follows the usual schedule. Injection is subcutaneous into the thigh, abdomen (at least 5 cm from the navel) or upper arm. Different injection sites should be rotated. After training self injection at home is possible.
Side Effects
Very common and common: upper respiratory tract infections (nasopharyngitis), rhinitis, oral candidiasis, injection site reactions, headache, diarrhoea, pruritus, urticaria.
Uncommon: oral herpes, otitis externa, conjunctivitis, muscle pain, back pain, tinea infections, folliculitis.
Rare but important: severe hypersensitivity reactions including anaphylaxis, reactivation of latent tuberculosis, opportunistic infections, exacerbation or new onset of chronic inflammatory bowel disease (especially Crohn's disease).
Candidiasis: IL 17A is crucial for host defence against Candida. Under secukinumab the incidence of oral, genital and cutaneous candidiasis is increased, although lower than under bimekizumab. Most cases are superficial and easy to treat.
Interactions
- Live vaccines (MMR, varicella, yellow fever, live zoster vaccine): avoid during therapy and for at least 5 half lives after end of treatment
- Inactivated vaccines: may be administered, immune response may be partially attenuated, influenza and pneumococcal vaccination recommended
- Methotrexate, ciclosporin, leflunomide, conventional DMARDs: combination possible in psoriatic arthritis, secukinumab monotherapy often provides effective control
- Other biological therapies (TNF inhibitors, IL 12/23 blockers): combination not recommended
- CYP substrates: biologics theoretically affect CYP enzymes via reduction of inflammation, usually not clinically relevant
Special Notes
Screening before therapy: tuberculosis test (IGRA or Mantoux), hepatitis B and C serology, HIV status in at risk patients. Check vaccination status and update live vaccines at least 4 weeks before starting therapy.
Chronic inflammatory bowel disease: In patients with known ulcerative colitis or Crohn's disease secukinumab should be used cautiously. Under IL 17A blockade new cases or exacerbations have been described, although the effect is complex. New or worsening abdominal symptoms during therapy require gastroenterological evaluation.
Pregnancy: data are limited, use only after careful benefit risk assessment. IgG antibodies cross the placenta in the second and third trimesters. Women of childbearing potential should use reliable contraception during therapy and for at least 20 weeks after the end of treatment. Breastfeeding: passage into breast milk has not been quantified reliably, breastfeeding is not generally recommended and should be individually weighed.
Monitoring: clinical response via PASI, BASDAI, DLQI, joint examination. Ask regularly about signs of infection. Blood count and liver values yearly or on clinical change. Oral mucosa and genital hygiene for recurrent candidiasis, topical antifungals if needed.
Pen and prefilled syringe: The autoinjector pen (SensoReady) and prefilled syringe are intended for self administration after training. Storage is in the refrigerator at 2 to 8 degrees Celsius. Bring to room temperature 15 to 30 minutes before use to reduce injection pain.
You may also be interested in
- Bimekizumab, IL 17A and IL 17F antibody
- Ustekinumab, IL 12/23 blocker in psoriasis and Crohn's disease
- Methotrexate, conventional DMARD in psoriatic arthritis
- Baricitinib, JAK inhibitor in rheumatological disease
- Etanercept, TNF receptor fusion protein
Frequently Asked Questions
How quickly does secukinumab work in psoriasis?
The first visible improvements often appear within the first 4 weeks. The full effect can be judged after 16 weeks, when 80 percent of treated patients reach a 75 percent improvement in the PASI score. If response is inadequate after 16 weeks, the indication can be reassessed or the dose increased.
Is secukinumab safe for long term use?
The safety data now extend over more than 10 years of continuous use. The frequency of serious infections, malignancies and cardiovascular events is not significantly increased. The main focus remains on superficial candidiasis and on the question of chronic inflammatory bowel disease.
When secukinumab, when bimekizumab?
Both act against IL 17A, and bimekizumab additionally blocks IL 17F. In comparative trials bimekizumab shows somewhat higher rates of PASI 90 and PASI 100, but also more frequent oral candidiasis. The choice depends on individual response, risk profile and adherence. Thanks to long market experience secukinumab remains a reliable first or second line option.
Can I be vaccinated during therapy?
Inactivated vaccines such as the yearly influenza vaccine, pneumococcus, COVID 19 and HPV are possible during therapy and are explicitly recommended, although the immune response may be somewhat attenuated. Live vaccines such as MMR, varicella, yellow fever or live zoster vaccine should ideally be updated before therapy starts and are contraindicated during treatment.
Sources
- EMA, Cosentyx (Secukinumab) EPAR
- AWMF, S3 guidelines on psoriasis and axial spondyloarthritis
- Gelbe Liste, secukinumab active substance profile
- BfArM, Federal Institute for Drugs and Medical Devices
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