Secukinumab
- Article Author:
- Shamma Aboobacker
- Article Author:
- Heidi Kurn
- Article Editor:
- Ahmad Al Aboud
- Updated:
- 6/28/2020 9:44:03 PM
- For CME on this topic:
- Secukinumab CME
- PubMed Link:
- Secukinumab
Indications
Secukinumab is a novel biologic agent that specifically targets interleukin-17 (IL-17) involved in a pathological process. It is a fully human monoclonal antibody. Recent literature refers to secukinumab as ‘a new kid on the block.’ Many clinical trials have demonstrated its efficacy for the management of plaque psoriasis in 2015, psoriatic arthritis, and ankylosing spondylitis in 2016. Additionally, the drug has a commendable safety profile.[1]
FDA approved indications:
- Moderate to severe psoriasis
- Hypertrophic palmoplantar psoriasis
- Generalized pustular psoriasis
- Psoriatic arthritis
- Ankylosing spondylitis
- Rheumatoid arthritis
- Systemic lupus erythematosus
- Familial Mediterranean fever
- Tumor necrosis factor receptor-associated periodic syndrome (TRAPS)
Psoriasis – Clinical studies have labeled secukinumab suitable as first-line therapy for moderate to severe cases of active, stable disease, hypertrophic palmoplantar psoriasis, and generalized pustular psoriasis in adult patients. In cases of prior failure to systemic therapies, contraindications, or intolerability to systemic agents, the drug is an acceptable choice for the initiation of biologic therapy.
Psoriatic arthritis – For active disease not responding to systemic agents in adult patients, secukinumab is prescribable as first-line therapy.
Ankylosing spondylitis – For active disease not responding to systemic agents or moderate-to-severe disease in adult patients are indications for secukinumab.[1]
Mechanism of Action
Interleukin-17 is a proinflammatory cytokine released by T-helper-17 (Th17) cells. Under the action of interleukin-6 and transforming growth factor-ß, CD4 T cells differentiate into Th17 cells and induce expression of interleukin-23 receptors (IL-23R) and IL-17. Apart from T-cells, mast cells and neutrophils also secrete IL-17.
Interleukin-17 encompasses a group of cytokines, IL-17A to IL-17F, with IL-17A being the key effector cytokine. Furthermore, IL-17A is described to be 10-30 more potent than IL-17F displaying a greater affinity to the interleukin-17 receptor (IL-17R).
The efferent pathway from binding to IL7R involves the secretion of chemokines (CCL20, CXCL1m CXCL8) that augments the inflammatory response while activating the innate immune system. The known effects of IL-17 become amplified by other cytokines such as tumor necrosis factor-a.[5]
Another effect of IL-17 is seemingly contradictory, being a stimulator of cancer cell invasion while promoting T-cell mediated tumor rejection. The significance is unknown due to a lack of evidence confirming a carcinogenic or protective.[6]
The basic notion behind the use of biologics is to block the disease process at a very early stage, being more specific and reducing the side effects of therapy. Secukinumab specifically targets IL-17A, thereby blocking its binding with IL-17R and expression of cytokines. This blockade normalizes the inflammatory processes and thus combats epidermal hyperproliferation, T-cell infiltration, and excessive expression of pathogenic genes.[5]
Administration
Secukinumab comes formulated as lyophilized powder of 150 mg in a vial, prefilled syringe, or a sensory ready pen that requires storage at a cool temperature (2 to 8 degrees C).[7]
Before administration, the pen or prefilled syringe must be kept aside for 20 to 30 mins until it reaches room temperature. Product reconstitution is with 10 ml sterile distilled water following which gentle stirring is performed to dissolve the powder and kept aside for 10 mins. The solution must be inspected to be free of residual particles or discoloration, and must administration must follow promptly.
Administration of secukinumab should be by a specialist physician while performing routine monitoring of the disease. It is given subcutaneously at sites such as upper arm, thigh, abdomen while avoiding sites of previous injection or tender, bruised, inflamed, indurated, or lesional skin.
The pharmacokinetic profile of the drug is such that it will attain peak concentrations after 5-6 days and a two-fold increase achieved after monthly dosing that becomes stable after 20 weeks. The average bioavailability is 73%, while the distribution is primarily peripheral, thereby increasing its specificity. The half-life is 27 days, with its elimination being dose and time-dependent.[5]
FDA approved indications with dosages[8]:
- Psoriasis – 300 mg subcutaneous injection at weeks 0, 1, 2, 3, 4, and every four weeks thereafter.
- Psoriatic arthritis – Two regimens may be followed, with or without the loading dose.
With loading dose; 150 mg given subcutaneously at weeks 0, 1, 2, 3, and 4: followed by a dose every four weeks.
Without loading dose; 150 mg via subcutaneous route at intervals of 4 weeks.
In case of no response, up-dosing to 300 mg is an option.
- Ankylosing spondylitis - Two regimens may be followed, with and without a loading dose.
With loading dose; 150 mg given subcutaneously at weeks 0,1,2,3, and 4: followed by a dose every four weeks.
Without loading dose; 150 mg via subcutaneous route at intervals of 4 weeks.
In case of no response, up-dosing to 300 mg is an option.
Intravenous dosing of 300 mg at 3-week intervals, followed by a maintenance dosing of 3 mg/kg every four weeks, showed long-term efficacy.
Adverse Effects
Secukinumab has a favorable safety profile; however, the following adverse effects have been reported[1][2][9]:
- Nasopharyngitis
- Diarrhea
- Upper respiratory tract infection
- Inflammatory bowel disease and Exacerbation of Crohn disease
- Urticaria and anaphylaxis
- Headache
- Pruritus
- Hypertension
- Arthralgia and back pain
- Cough
- Rhinorrhea
- Injection site reaction
- Infections
- Pyoderma
- Candidiasis
- Malignancies
- Nonmelanoma skin cancer (basal cell carcinoma, squamous cell carcinoma)
- Melanoma
- Bladder cancer
- Thyroid cancer
- Neutropenia
Contraindications
The absolute contraindications for the use of biologics are the presence of active infections, more importantly, latent or active tuberculosis, hepatitis B, C and HIV, and hypersensitivity to secukinumab or latex.
Other contraindications include[10]:
- PUVA sessions
- Premalignant conditions
- Demyelinating disease
- Optic neuritis
- Multiple sclerosis
- Children
- Pregnancy and lactation
- Congestive heart failure
- Fever
- Jaundice or marked liver enzyme elevations
Pregnancy – As an IgG1 molecule, secukinumab could cross the placenta, but mostly in the third trimester. Studies do not indicate the harmful effects of secukinumab on pregnancy or fetal development. However, a precautionary measure is to avoid use in pregnancy.
Monitoring
Baseline Monitoring
- Complete blood count and Hemogram
- Erythrocyte sedimentation rate or C-reactive protein
- Liver function test
- Renal function test and urinalysis
- Serum electrolytes
- Anti-nuclear and anti-dsDNA antibodies
- Screening for hepatitis and HIV infection
- Chest x-ray
- Tuberculin skin testing or Quantiferon Gold test
- Pregnancy test in females of childbearing age
If indicated – Serology for varicella-zoster and measles.
Ongoing Monitoring
Evaluation of response to treatment is measurable by respective assessment scores, i.e., Psoriasis Area and Severity Index (PASI), Dermatology Life Quality Index (DLQI) at three months initially and subsequently every six months.
Complete blood count and hemogram repeated at three months and every six months after that
Liver function tests, renal function tests, serum electrolytes, and urinalysis evaluations should be at three months and every six months after.[10][11]
Toxicity
The safety profile of secukinumab leaves it highly recommendable. Since secukinumab interferes with the normal immune process, it enhances the risk of infections, including staphylococcal and candidal, however mild disease results and not disseminated.
Concerning pregnancy, a few studies have outlined pregnancy occurring while on secukinumab therapy with no congenital anomalies or risk of abortion, and thereby, strict contraception is not the stated case. However, studies mention potential deleterious effects if taken during the third trimester due to placental transfer, and therefore the drug should be withdrawn or considered contraindicated in pregnancy and lactation.
Another possible toxic effect is the carcinogenic potential, with existing reports of malignancies such as non-melanoma skin cancers (basal cell carcinoma and squamous cell carcinoma), melanoma, bladder cancer, and thyroid cancer.[1]
Enhancing Healthcare Team Outcomes
The common notion related to biologic therapy is the necessity for lifelong or long-term treatment, the failure of which can lead to incomplete resolution or recurrences. With secukinumab, relapses and recurrences are less frequent and can are preventable with a maintenance regime of fixed-interval dosing. Also, following patient education by an interprofessional team of a nurse, pharmacist, and physician, subsequent doses can be self-administered, thereby increasing patient compliance and adherence.[5] The pharmacist can verify all dosing, check for drug-drug interactions, and counsel the patient on adverse events and signs that would warrant contacting their clinician. Nurses can also provide counsel, monitor therapeutic progress as well as for adverse events, and verify patient compliance. These examples show how an interprofessional team approach can optimize outcomes with secukinumab therapy. [Level V]
Patients on active secukinumab therapy should avoid live vaccines and contact with infectious agents due to the markedly depressed immunity that can lead to infection. Furthermore, the administration of non-live vaccines is also discouraged due to the unlikelihood of mounting a desired immune response.[10]
The likelihood of a history of latent or active tuberculosis with no confirmation of complete therapy or recent travel to a country with a high prevalence of tuberculosis may warrant a course of empiric anti-tubercular treatment.