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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 and dose frequency (see Further information).

The Surgical Team and patient’s Rheumatologist 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 anakinra 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 anakinra can be managed on less than 15mg prednisolone (or equivalent).

Minor procedures

Consider continuing anakinra 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 1 day after administration of daily anakinra.

Patients taking narrow therapeutic index medication

Some manufacturers predict that stopping or starting bDMARD therapy may affect expression of cytochrome P450 enzymes, which theoretically may affect metabolism of other medicines the patient may be taking. Additional monitoring may be needed in patient’s taking concomitant narrow therapeutic medication e.g. phenytoin, warfarin, theophylline when stopping anakinra before surgery.

Emergency surgery 

Withhold any doses due in the immediate post-operative period. Monitor closely for infection if patient has received a dose of anakinra in previous day.

Perioperative considerations

Control of body temperature and avoidance of blood transfusion may minimise the risk of infection.

Post-operative advice

If stopped, the literature recommends recommencing 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. However, we advise discussing with Surgeon and Rheumatologist on a case-by-case basis as withholding for this length of time is likely to result in perioperative disease flare given the short half-life of anakinra.

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

Anakinra is used for rheumatoid arthritis, Still’s disease and cryopyrin-associated periodic syndromes. Doses are administered daily as it has a short half-life (4 – 6 hours). 

Rationale for recommendations - risk of infection versus risk of disease

Currently there is limited evidence regarding the risk of infection in patients who continue biologic disease modifying anti-rheumatic drugs (bDMARDs), e.g. anakinra 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 recommendation to continue anakinra prior to minor procedures is extrapolated from the American Academy of Dermatologists / National Psoriasis Foundation (ADD / NPF) guidelines who advise biologics can safely be continued before minor surgery. The American College of Rheumatology / American Association of Hip and Knee Surgeons (ACR / AAHKS) advise planning surgery in most patients for after one dose of anakinra has been missed when the nadir of the drug is at its lowest. Similarly, the German Society for Rheumatology (GSR) advise a pause of 1 – 2 days should be sufficient due to the short half-life. 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.

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. 

References

1. Albrecht, K. Poddubnyy, D. Leipe, J. et Perioperative management of patients with inflammatory rheumatic diseases: Updated recommendations of the German Society for Rheumatology. Zeitschrift fur Rheumatologie. 2022, 82: 1-11 doi:10.1007/s00393-021-01150-9
   
   
2. Baxter K, Preston CL (eds), Stockley’s Drug Interactions (online) London: Pharmaceutical Press. http://www.medicinescomplete.com [Accessed 6^th February 2024]
   
   
3. Buchbinder, R. Glennon, V. Johnston RV. et Australian recommendations on perioperative use of disease-modifying anti-rheumatic drugs in people with inflammatory arthritis undergoing elective surgery. Internal Medicine Journal. 2023,53:1248–1255 doi:10.1111/imj.16073
   
   
4. 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
   
   
5. In: Brayfield A (Ed), Martindale: The Complete Drug Reference. London: The Royal Pharmaceutical Society of Great Britain. Electronic version. Truven Health Analytics, Greenwood Village, Colorado, USA. Available at: http://www.micromedexsolutions.com [Accessed 29^th January 2024]
   
   
6. Joint Formulary Committee. British National Formulary (online) London: BMJ Group and Pharmaceutical Press http://www.medicinescomplete.com [Accessed 6^th February 2024]
   
   
7. Menter, A. Strober, BE. Kaplan DH. et 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:10.1016/j.jaad.2018.11.057
   
   
8. Moreira P, Correia A, Cerquerira M, Gil M. Perioperative management of disease-modifying antirheumatic drugs and other immunomodulators. ARP Rheumatol. 2022; 3: 218-224
   
   
9. Summary of Product Characteristics – Kineret® (anakinra) 100 mg solution for injection in a pre-filled syringe. Swedish Orphan Biovitrum Ltd. Accessed via medicines.org.uk 06/02/24[date of revision of the text June 2023]