Q&A: Side Effects of Anti-TNF Therapy

Tumor necrosis factor-a (TNF-a) was originally named for its ability to trigger necrosis of transplanted tumor cells in mice. The purification and cloning of a molecule called “cachectin”, which causes wasting in chronic diseases, was subsequently found to be identical to TNF-a. TNF is produced primarily by macrophages and, to a lesser extent, by lymphocytes.

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In this article:
What is a TNF Inhibitor?
MCQ exam: clinical scenario
MCQ exam: answer
MCQ exam: explanation

What is a TNF Inhibitor?

A TNF inhibitor is a pharmaceutical drug that suppresses the physiologic response to Tumor Necrosis Factor (TNF), which is part of the inflammatory response. In other words, a TNF inhibitor helps stop inflammation.

TNF is involved in autoimmune and immune-mediated disorders such as rheumatoid arthritis, ankylosing spondylitis, inflammatory bowel disease (Crohns and ulcerative colitis), psoriasis, hidradenitis suppurativa and refractory asthma, so TNF inhibitors may be used in their treatment as it reduces/stops inflammation and can stop disease progression by targeting the inflammation-causing substance, Tumor Necrosis Factor (TNF).

However, TNF inhibitors have very important side effects that occur in some people who are on treatment with them.

MCQ exam: clinical scenario

A 64 year-old woman with severe rheumatoid arthritis has severe fatigue and is found to have multiple swollen lymph nodes. She is currently managed with infliximab.

She is found to have antinuclear antibody positivity.

What is the likely diagnosis?

a) Lymphoma
b) Generalised tuberculosis
c) SLE-type syndrome
d) Reactivation of rheumatoid disease
e) Chronic myeloid leukaemia

MCQ exam: answer

The correct answer is A.
Lymphoma is the correct answer.

MCQ exam: explanation

Early experience with antiTNF-a therapy has identified 7 types of adverse effects that seem to be of particular concern:

(1) infection including sepsis and tuberculosis (especially reactivation of latent tuberculosis)
(2) malignancies such as lymphoma
(3) haematological disorders such as anaemia and pancytopenia
(4) demyelinating disorders and neuropathy
(5) exacerbation of CHF (congestive heart failure)
(6) production of autoantibodies and autoimmune responses (immunosuppression)
(7) infusion related problems (as hypersensitivity - pain, erythema, localized rash and haemorrhage at injection site)

Use of these agents is also associated with an increased development of antinuclear antibody positivity. Although this is insignificant in many patients, in some cases it may be associated with a lupus-like syndrome that appears transient and resolves after drug discontinuation.

Reference(s)
1). American College of Rheumatology: TNF Inhibitors. Available online: https://www.rheumatology.org/I-Am-A/Patient-Caregiver/Treatments/TNF-Inhibitors
2). Johns Hopkins Arthritis Center: Anti-TNF Therapy for Rheumatoid Arthritis. Available online: https://www.hopkinsarthritis.org/arthritis-info/rheumatoid-arthritis/ra-treatment/anti-tnf-therapy-for-ra/
3). Scheinfeld N (September 2004). "A comprehensive review and evaluation of the side effects of the tumor necrosis factor blockers etanercept, infliximab and adalimumab". J Dermatolog Treat. 15 (5): 280–94. doi:10.1080/09546630410017275. PMID 15370396.