DISCUSS IN DETAIL REGARDING SAFETY CONCERNS WITH USE OF ANTI TNF ALPHA THERAPY ?
A 1 INTRODUCTION
1 Tumour necrosis factor alpha or TNFα is a cytokine.
2 Cytokines are substances released by the body during inflammation.
3 Inflammation is a normal process generated by the body to fight against harmful bacteria and viruses.
4 Normally, this inflammation is controlled and regulated.
5 In rheumatoid arthritis this process breaks down, therefore the joints of patients with rheumatoid arthritis become inflamed.
6 An excessive amount of TNFα is present in the blood and joints of patients with rheumatoid arthritis.
7 TNFα is a particularly powerful cytokine because it causes the release of other cytokines from the body (such as IL1 and IL6).
8 So , Blocking TNFα can reduce inflammation and joint damage.
9 Currently, there are five licenced treatments, etanercept (Enbrel), infliximab (Remicade), adalimumab (Humira), certolizumab pegol (Cimzia) and golimumab (Simponi) that can block the effect of TNFα.
10 TNF inhibitor is a pharmaceutical drug that suppresses the physiologic response to tumor necrosis factor (TNF), which is part of the inflammatory response.
11 TNF is involved in autoimmune and immune-mediated disorders such as rheumatoid arthritis, ankylosing spondylitis, inflammatory bowel disease, psoriasis, hidradenitis suppurativa and refractory asthma, so TNF inhibitors may be used in their treatment.
12 The important side effects of TNF inhibitors include lymphomas, infections (especially reactivation of latent tuberculosis), congestive heart failure, demyelinating disease, a lupus-like syndrome, induction of auto-antibodies, injection site reactions, and systemic side effects.
13 Inhibition of TNF effects can be achieved with a
A ) monoclonal antibody such as infliximab(Remicade), adalimumab (Humira), certolizumab pegol (Cimzia), and golimumab (Simponi),
B ) with a circulating receptor fusion protein such as etanercept (Enbrel).
C ) Thalidomide (Immunoprin) and its derivatives lenalidomide (Revlimid) and pomalidomide (Pomalyst, Imnovid) are also active against TNF.
14 Naturally acting anti TNF products - CURCUMIN ( TURMERIC ) , CATECHINS ( GREEN TEA ) , CANNABIS
15 Majority of side effects being reported is from the use of etarnecept such as heart failure , drug induced lupus , demyelinating disorders
16 are not recommended in demyelinating disorders
TYPES OF ANTI TNF
1 Adalimumab is an anti-TNF-alpha recombinant human IgG1 monoclonal antibody.
2 Etanercept is recombinant human TNF receptor fusion protein (consisting of p75 TNF-alpha receptor and human IgG) which inhibits the binding of TNF to its cell surface receptor.
3 Infliximab is a chimeric anti-TNF-alpha monoclonal antibody
1 RHEUMATOID ARTHRITIS
2 HIRADENITIS SUPPURTIVA
3 PLAQUE TYPE PSORIASIS
4 induction and maintenance of remission in luminal Crohn's disease.
5 JUVENILE RA
6 PSORIATIC ARTHRITIS
7 ANKYLOSING SPONDYLITIS
1 INCREASED RISK OF SERIOUS INFECTIONS LIKE PNEUMONIA , OPPORTUNISTIC INFECTIONS - Tuberculosis , listerosis , histoplasmosis
A ) TNF-α plays an important role in TB pathogenesis and in particular granuloma formation, containment and clearance of TB infection
B ) Most cases of TB occurred within the first 6 months of anti-TNF therapy and more often present as disseminated, extrapulmonary or atypical mycobacteria compared with the rest of the population.
2 NON HODGKIN LYMPHOMA - 20 to 25 fold
A ) Of the lymphomas, 54% were detected within 8 weeks of anti-TNF treatment initiation, and two patients remitted after cessation of treatment.
B ) Patients with previous cancer have to be monitored closely because of the possibility that they might be more vulnerable to subsequent tumor development on anti-TNF drugs.
C ) the risks appear to be dose dependent, with those on high-dose therapy (defined as ≥6 mg/kg infliximab every 8 weeks or ≥40 mg adalimumab every other week) having the greatest risk
3 NON MELANOTIC SKIN CANCER AND MELANOMA
A ) TNF-α plays an important role in surveillance of malignancy and hence there is a theoretical risk of increased tumor formation with anti-TNF-α agents.
4 HEPATOSPLENIC T CELL LYMPHOMA
A ) In RA, monitoring should continue on a six-monthly basis using the DAS28 calculator. Treatment should be discontinued if adequate response is not maintained.
B ) In juvenile arthritis, etanercept should be tried for six months before stopping and continued for up to two years although, again, disease activity and individual response should be taken into consideration.
C ) In Crohn's disease, treatment should be continued for 12 months or until treatment fails, whichever is the shorter. Loss of response to anti-TNF-alpha drugs is becoming an increasing clinical problem; the reason for this unknown.
D ) In psoriatic arthritis, treatment should be stopped after 12 weeks if there is no adequate response, unless the patient's psoriasis start to improve.