Etanercept: a TNF blocker given by injection for inflammatory arthritis

The UK product information, here for the biosimilar Benepali, places etanercept among the immunosuppressant TNF-alpha inhibitors. TNF is a dominant cytokine in the inflammatory process of rheumatoid arthritis, and raised levels are also found in the joint lining and psoriatic plaques of people with psoriatic arthritis and in tissues in axial spondyloarthritis. Etanercept soaks up TNF and so reduces inflammation.

In rheumatoid arthritis it has been shown, alone or with methotrexate, to reduce the rate of progression of joint damage on X-ray and to improve physical function.

In adults, etanercept in combination with methotrexate is indicated for moderate to severe active rheumatoid arthritis when the response to DMARDs including methotrexate has been inadequate, and it can be given alone if methotrexate is not tolerated or inappropriate. It is also indicated for severe, active and progressive rheumatoid arthritis not previously treated with methotrexate, and for active and progressive psoriatic arthritis after an inadequate response to previous DMARD therapy.

In children it is indicated for polyarthritis and extended oligoarthritis from age 2 and for psoriatic arthritis and enthesitis-related arthritis in adolescents from age 12 in specified circumstances. The full list also covers axial spondyloarthritis and other conditions, and your specialist decides which indication applies.

Patients should be evaluated for infections before, during and after treatment, bearing in mind that the half-life of etanercept is about 70 hours. Serious infections, sepsis, tuberculosis and opportunistic infections, including invasive fungal infections, listeriosis and legionellosis, have been reported. If a serious infection develops, administration should be discontinued.

Before starting, everyone must be evaluated for both active and latent tuberculosis, with history and appropriate tests. Active tuberculosis means etanercept must not be started, and latent tuberculosis needs treatment first. Reactivation of hepatitis B in previously infected people has been reported, and worsening of hepatitis C has also been reported. Seek advice if you develop a persistent cough, weight loss or low-grade fever during or after treatment.

The most commonly reported effects are injection site reactions (pain, swelling, itching, redness and bleeding), and infections such as upper respiratory tract infections, bronchitis, bladder infections and skin infections. Serious reactions reported include serious infections, tuberculosis, and, rarely, serious blood, nerve and autoimmune reactions, including pancytopenia and very rare cases of aplastic anaemia.

Because TNF blockers affect the immune system, tell your team promptly about fever, a persistent cough, painful skin infections, unexplained bruising or bleeding, or new numbness, tingling, vision changes or weakness.

Combining etanercept with anakinra was associated with a higher rate of serious infection, and concurrent abatacept increased serious adverse events without added benefit. Adding etanercept to established sulfasalazine was associated with a statistically significant fall in white blood cell counts. No interactions were observed with glucocorticoids, salicylates (other than sulfasalazine), NSAIDs or analgesics, and no clinically significant pharmacokinetic interactions were seen with methotrexate, digoxin or warfarin.

Live vaccines are a standard concern with TNF blockers, so tell anyone giving a vaccination that you use etanercept and follow your specialist team's vaccination advice.

Women of childbearing potential should consider appropriate contraception during therapy and for three weeks after stopping. Animal studies showed no evidence of harm to the foetus, and observational data have been examined, but etanercept crosses the placenta and has been detected in the serum of infants born to treated mothers, whose clinical impact is unknown; infants may be at increased risk of infection.

Etanercept has been detected at low levels in human milk. Exposure in a breastfed infant is expected to be low because it is largely degraded in the gut, but limited data exist, so your specialist advises on feeding. Effects on fertility have not been studied.