|Year : 2015 | Volume
| Issue : 1 | Page : 50-52
Etanercept: Indian perspective
Murlidhar Rajagopalan1, Resham Vasani2
1 Consultant Dermatologist, Skin Clinic, Chennai, Tamil Nadu, India
2 Consultant Dermatologist, Anand Polyclinic, Matunga, Mumbai, Maharashtra, India
|Date of Web Publication||1-Dec-2015|
C-1, 22, Karmakshetra, Near Shanmukhananda Hall, Sion, Mumbai - 400 037, Maharashtra
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Rajagopalan M, Vasani R. Etanercept: Indian perspective. Indian J Drugs Dermatol 2015;1:50-2
| What Is a Biologic?|| |
Biologicals are large molecules derived from living cells and are used in the treatment, diagnosis or prevention of disease. They include therapeutic proteins, deoxyribonucleic acid vaccines, monoclonal antibodies and fusion proteins. Biologic medicines are often 200–1000 times the size of a small molecule drug and are far more complex structurally. These are almost always injected in the patient's body. The future biologicals may be smaller molecules.
| What Is the Difference between a Biological and a Biosimilar?|| |
A biosimilar is a biological medicinal product that contains a version of the active ingredient of an already authorized original biological medicinal product. The active ingredients are similar but not identical copies of the originator biologic. There are minor differences in the clinically inactive components for which there are said to be no clinically meaningful differences between the biological product and the reference product in terms of the safety, purity, and potency of the product. Such medicines are labeled as "Biosimilar."
| What Is Etanercept?|| |
Etanercept is recombinant human soluble tumor necrosis factor (TNF)-α receptor antagonist and is a dimeric fully human fusion protein produced in Chinese hamster ovary. Etanercept binds to soluble TNF-α more than membrane-bound TNF-α. The binding is not permanent and in situ ations where it is required, the complex can be separated spontaneously (i.e., especially important in the context of tuberculosis [TB]) preventing cytokine to bind to any cell surface receptor.
| What Are Indications of Etanercept in Dermatology?|| |
The Food and Drug Administration-approved indications of etanercept are psoriasis and psoriatic arthritis. The off-label indications include neutrophilic dermatoses, autoimmune bullous disorders, sarcoidosis, connective tissue disorders, graft versus host disease, hidradenitis suppurativa, multicentric reticulohistiocytosis, and inflammatory acne syndromes such as Synovitits, Acne, Pustulosis, Hyperostosis, and Osteitis (SAPHO) syndrome. It has been tried in early drug reactions as well.
| How Is Etanercept Available?|| |
Etanercept 25 mg is available as a sterile preservative-free lyophilized powder that is reconstituted with 1 ml of supplied bacteriostatic water. The reconstituted solution has to be stored in the refrigerator and not frozen. It is stable for up to 14 days in the refrigerator. It is also available as a prefilled syringe of 50 mg of etanercept. It is also to be stored in the refrigerator and not frozen. It should be allowed to return to room temperature for about 15 min to decrease injection-related pain.
| What Are the Cases of Psoriasis or Psoriatic Arthritis Where One Would Prefer Etanercept?|| |
Classically, I would use etanercept or a biological in cases where the disease is resistant to conventional drugs, or the prolonged administration of conventional drugs has produced end-organ toxicity.
| What Is the Dose of Etanercept?|| |
It can be started at the dose of 50 mg twice a week initially. It can be further decreased to 50 mg/week which can be further reduced to 25 mg once weekly or 50 mg every other week depending upon the clinical response. The site of injection is thigh/abdomen/upper arms. The site of injection is rotated to at least 1 inch apart from the last site of injection.
| Is the Dosing Pattern Followed for the Indian Scenario Different? If Yes, Please Elaborate the Dose and the Reasons for the Same|| |
The dosing pattern in India is influenced by cost factors. Many doctors use it once a week with variable classification criteria for psoriatic arthritis and Psoriasis Area Severity Index (PASI) responses. However, the effect is sometimes better in some patients than in others; hence doctors do try and reduce the dose or increase the gap between doses to achieve a good Dermatological Quality of Life Index. There are no trials comparing varying doses. As far as possible, it is better to adhere to the designated dose schedule.
| What Are the Contraindications of Etanercept?|| |
The contraindications include,
- Known hypersensitivity
- Concurrent administration of interleukin-1 receptor antagonist
- Active infection
- Chronic and localized infections including TB
- Malignancy within 5 years of therapy being initiated
- TB (especially in India)
- Multiple sclerosis
- Heart failure.
| What Are the Investigations Required to Perform Before Administration of Etanercept Especially in the Indian Setting?|| |
The investigations recommended include hemogram, liver function tests, renal function tests, hepatitis B and C serologies, urine routine and microscopy and screening for TB.
| How Should We Screen for Underlying Tuberculosis?|| |
In the Indian setting, it is extremely important to screen for active and latent TB. The investigations include,
- A detailed history should be elicited of prior TB, history of anti-TB therapy, compliance to treatment
- Thorough physical examination
- X-ray chest
- Tuberculin test – not useful in the Indian setting. Reasons are:
- Universal Bacillus Calmette–Guérin (BCG) vaccination renders purified protein derivative (PPD) skin test positive for several years. PPD test carried out 15 years or more after BCG vaccine is not influenced by vaccination
- Infection with mycobacteria other than TB may be responsible for positive Mantoux test (MT)
- It can be false negative because of immunosuppressants such as methotrexate or corticosteroids. Hence, it should be performed at least a month after stopping corticosteroids and at least 3 months after stopping other immunosuppressants
- Quantiferon gold assay is performed in most of the clinical trials of biologics in India. Quantiferon gold is useful especially in patients who are immunosupprressed by previous therapy or in whom a Mantoux is difficult to interpret because of previous BCG or immunosuppression. This test is useful mainly to detect latent TB. Biologicals can reactivate latent TB hence the importance of this test.
All patients with a positive MT (>5 mm) or past history of TB; should receive prophylactic anti-TB therapy. Prophylactic therapy is 9 months of daily isoniazid or 6 months of isoniazid with rifampicin.
If the patient is asymptomatic, but X-ray chest is abnormal, and there is the absence of constitutional symptoms of fever, anorexia, or weight loss and one should look for progression by doing X-ray chest every 3 months. Anti-TNF-α should be withheld until active TB is excluded.
If a patient develops active TB during therapy, he/she should receive full anti-TB chemotherapy and discontinue anti-TNF-α therapy.
| What Are the Adverse Effects of Etanercept?|| |
- Injection site reactions are the most commonly reported the adverse effect of etanercept. It can appear as an erythematous, edematous patch, or plaque which may be asymptomatic, tender or pruritic. In my practice, I have not observed any injection reaction until date. The treatment includes warm water compresses, topical corticosteroids, and oral antihistamines
- Patients with underlying comorbidities that predispose them to infections like diabetes mellitus should be monitored closely while on etanercept. Precipitation of TB is an important drawback of etanercept therapy. This holds true for any biological
- Etanercept should be used with caution in a patient with a personal or family history of multiple sclerosis or other demyelinating diseases since it can precipitate or aggravate the same
- Autoimmunity or antidrug antibodies are produced in a few patients on etanercept but these autoantibodies are not neutralizing unlike monoclonal antibodies nor they are found to be associated with ineffective treatment. Positive anti-nuclear antibodies are reported, but in very few cases actually translate into drug induced lupus and thankfully the antibodies disappear after discontinuation of treatment
- Etanercept should be used with caution in patients with cardiac failure since it can aggravate the same.
| Why Do Tumor Necrosis Factor-α Inhibitors Increase the Chance of Tuberculosis?|| |
TNF-α and interferons cause oxidative damage to the mycobacterial constituents. TNF-α also mediates macrophage apoptosis, stimulates the release of inflammatory cytokines of CD-8 cytotoxic cells, helps in granuloma formation. Hence, TNF-α blockers increase the chances of reactivation of latent TB.
| What Is Your Experience Regarding Safety of Etanercept? How Long Do You Monitor Patient for Tuberculosis?|| |
I feel etanercept is a safe and effective drug, I have used it for more than 10 years, and there are no major safety issues as yet. Monthly examination and every 3-month blood workup for complete blood count, liver function tests, C-reactive protein, and urine routine are enough. We do not need very detailed workups every time.
| Why Etanercept Has Better Safety Profile Than Others?|| |
It binds more to soluble receptors and is easily dissociated from the TNF molecule. This confers an advantage in safety. Although it binds to membrane-bound receptors, it does not cause cell apoptosis, which is also an advantage in terms of safety.
| Can You Please Share the Average Cost Incurred to the Patient on Etanercept Therapy?|| |
Etanercept is expected to be given to the patient for at least 6 months. The cost of the biological for this period works out to approximately Rs. 5 lakhs but discounts of up to 20% are available. The biosimilar variant is about 20% cheaper than the discounted price of the biological. However, I cannot comment on the efficacy comparison as I have not used the biosimilar variant, and there is no literature on it as yet.
| How Does Etanercept Compare Vis-A-Vis Infliximab?|| |
There is no evidence to suggest that one anti-TNF-α therapy is more efficacious than others. Infliximab is useful when etanercept has failed and vice versa. However, though there are no direct head to head trials, a meta-analysis of PASI scores do indicate that infliximab is definitely superior to etanercept in terms of efficacy but not necessarily in terms of safety.
There are more cases of TB reported with infliximab than etanercept because,
- Dose of infliximab is usually higher than the dose used for etanercept
- Infliximab has higher half life
- Infliximab has high association rates and very low dissociation rates
- Infliximab produces continuous and irreversible blockade of TNF-α than etanercept
- Infliximab binds monomeric (inactive) and trimeric (active) forms of soluble TNF while etanercept is more likely to bind to the active trimeric form
- Infliximab forms stable complexes with soluble TNF-α while etanercept tends to form relatively unstable complexes allowing dissociation of TNF-α
- Infliximab but not etanercept fix complement and lyse cells that express TNF-α on their surface. Therefore, peripheral CD4 count decreases with infliximab and increases with etanercept.
Thus, in terms of efficacy, infliximab scores over etanercept. However, as there is more risk of TB, etanercept is more appropriate in Indian settings.
| Where Does Etanercept Stand in the Treatment of Psoriasis in India?|| |
In India, etanercept stands tall in the list of systemic agents for psoriasis as it is more effective and relatively safe for use in extensive psoriasis. However, the cost is the main limiting factor.
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Conflicts of interest
There are no conflicts of interest.