Brands of this drug
Benepali, Enbrel, Erelzi
Issues for surgery
Risk of perioperative flare in disease activity (potentially leading to an increase in glucocorticoid use) if omitted.
Risk of post-operative infection if continued.
Advice in the perioperative period
Elective surgery
Establish indication, dose frequency and brand of biosimilar (see Further information).
The Surgical Team and patient’s Rheumatologist / Dermatologist along with the patient should be involved in the planning for elective surgery to balance the potential benefit of preventing post-operative infection by stopping etanercept against the risk of developing severe or unstable disease.
Modifiable risk factors for perioperative infection, such as glycaemic control and smoking should ideally be addressed prior to surgery.
Glucocorticoid use is associated with increased perioperative infection in a dose dependent manner. Where possible consider delaying elective surgery until patients taking etanercept can be managed on less than 15mg prednisolone per day (or equivalent).
Minor procedures
Consider continuing etanercept before low-risk surgery (i.e. surgery without a break in sterile technique, during which the respiratory, gastrointestinal, and genitourinary tracts are not entered) e.g. endoscopy, bronchoscopy, hysteroscopy, cystoscopy, breast biopsy, dermatologic or ophthalmological procedures.
All other procedures
Surgery should be scheduled to enable the patient to miss ONE dose (i.e., scheduling surgery for a minimum of 8 days after weekly etanercept). For patients taking etanercept twice weekly the guidelines also suggest a minimum 8 day gap, however in practice it may be necessary to discuss with Rheumatologist / Dermatologist.
EXCEPT: -
If the Surgical Team deem the procedure to be of especially high infection risk, consider stopping 3-5 half-lives before surgery. Be mindful that a flare in disease activity may occur, which may result in glucocorticoids being administered, further increasing the infection risk (see Further information).
Emergency surgery
Withhold any doses due in the immediate post-operative period. Monitor closely for infection if patient has received a dose of etanercept in the previous week.
Perioperative considerations
Control of body temperature and avoidance of blood transfusion may minimise the risk of infection.
Post-operative advice
If stopped, recommence post-operatively when there is evidence of wound healing, all sutures and staples are out, there is no significant swelling, erythema, or drainage, and there is no ongoing nonsurgical site infection. This is typically around 14 days post-operatively.
Interactions with common anaesthetic agents
None.
Interactions with other common medicines used in the perioperative period
None.
Further information
Indications, dosing frequency and half-life
Etanercept is used for plaque psoriasis, rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis and non-radiographic axial spondyloarthritis. Doses are typically administered twice weekly or weekly. Etanercept has a half-life of 70hours.
Biosimilar medication
Etanercept has several biosimilar brands which are considered to be therapeutically equivalent to the originator biological medicine within their authorised indications. However, biosimilar medicines must be prescribed by brand name to prevent inadvertent switching.
Rationale for recommendations - risk of infection versus risk of disease
Inflammatory arthritis
Currently there is limited evidence regarding the risk of infection in patients who continue biologic disease modifying anti-rheumatic drugs (bDMARDs), e.g. etanercept perioperatively. Several meta-analyses have been conducted; however, the methodology of the underpinning studies is not comparable with respect to confounding factors and stopping duration. Thus, recommendations from eminent societies are largely based on expert opinion.
The British Society for Rheumatology (BSR), American College of Rheumatology / American Association of Hip and Knee Surgeons (ACR / AAHKS) and German Society for Rheumatology (GSR) advise planning surgery in most patients for after one dose of etanercept has been missed when the nadir of the drug is at its lowest. This pragmatic approach seeks to minimise the stopping period and thus the risk of a perioperative flare in symptoms which would result in an increase in glucocorticoid use, which would further increase the risk of infection. However, they caveat that if surgery is associated with a very high risk of infection consideration should be given to stopping for 3-5 half-lives, but this must be balanced against the risk of perioperative flare.
Conversely the Australian recommendations suggest it may be possible to continue bDMARDs perioperatively (unless individuals have a high risk of infection or where impact of infection would be severe when surgery should be timed as outlined above). Whilst there is little evidence to support or refute this recommendation, there may be more evidence for this once the PERISCOPE trial has been evaluated. This clinical trial involves randomising patients on bDMARDs for inflammatory arthritis to either continue or stop bDMARDs prior to elective orthopaedic surgery, including arthroplasty, however patient recruitment is just starting and publication is not anticipated until at least 2026.
Psoriasis
The evidence for risk of post-operative infection in patients with psoriasis is minimal and is often extrapolated from other populations. The American Academy of Dermatologists / National Psoriasis Foundation (ADD / NPF) advise biologics can safely be continued before minor surgery. However, unlike the rheumatology societies the British Association of Dermatologists and AAD / NPF are more cautious with their recommendations for other surgery, suggesting most patients should stop biologic therapy for a period of time equivalent to 3 - 5 half-lives before surgery or the length of the treatment cycle, whichever is longer. Given the lack of robust evidence that a longer interruption of treatment is beneficial this seems an overly cautious approach, and risks a perioperative flare, which is likely to necessitate glucocorticoid use and subsequently increase the risk of infection. Therefore, for simplicity, and in the absence of evidence to the contrary we have extrapolated the recommendations for rheumatology patients to this patient population.
References
Albrecht, K. Poddubnyy, D. Leipe, J. et al. Perioperative management of patients with inflammatory rheumatic diseases: Updated recommendations of the German Society for Rheumatology. Zeitschrift fur Rheumatologie. 2022, 82: 1-11. DOI.org/10.1007/s00393-021-01150-9
Al-Janabi, A. and Yiu, ZZN. Biologics in Psoriasis: Updated Perspectives on Long-Term Safety and Risk Management. Psoriasis (Auckl). 2022; 12:1-14 DOI:10.2147/PTT.S328575
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Goodman, SM. Springer, BD. Chen AF. American College of Rheumatology and American Association of Hip and Knee Surgeons (AAHKS) 2022 American College of Rheumatology / American Association of Hip and Knee Surgeons Guideline for the Perioperative Management of Antirheumatic Medication in Patients with Rheumatic Diseases Undergoing Elective Total Hip or Total Knee Arthroplasty. 2022;74(9):1399-1408 DOI 10.1002/acr.24893
Holroyd, CR. Seth, R. Bukhari, M. et al. The British Society for Rheumatology biologic DMARD safety guidelines in inflammatory arthritis. Rheumatology. 2019; 58:220-226 DOI.org/10.1093/rheumatology/key207
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Menter, A. Strober, BE. Kaplan DH. et al. Derm Joint AAD-NPF guidelines of care for the management and treatment of psoriasis with biologics. J Am Acad Dermatol. 2019; 80:1029-1072 DOI.org/10.1016/j.jaad.2018.11.057
Moreira P, Correia A, Cerquerira M, Gil M. Perioperative management of disease-modifying antirheumatic drugs and other immunomodulators. ARP Rheumatol. 2022; 3: 218-224.
Pandit, H. & Mankia, K. PERI-operative biologic DMARD management: Stoppage or COntinuation during orthoPaEdic operations: The PERISCOPE trial. Protocol v1.0 (February 2023).
Smith, CH. Yiu, ZZN. Bale, T. et al. British Association of Dermatologists guidelines for biologic therapy for psoriasis 2020: a rapid update. Br J Dermatol. 2020;183(4):628–637. DOI: 10.1111/bjd.19039
Summary of Product Characteristics – Benepali (etanercept) 50 mg solution for injection in pre-filled pen. Biogen Biosimilars. Accessed via www.medicines.org.uk 29/01/24 [date of revision of the text September 2023]
Summary of Product Characteristics – Enbrel (etanercept) 50 mg solution for injection in pre-filled pen. Pfizer Limited. Accessed via www.medicines.org.uk 29/01/24 [date of revision of the text December 2023]