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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 / 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 ixekizumab 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 ixekizumab can be managed on less than 15mg prednisolone (or equivalent).

Minor procedures

Consider continuing ixekizumab 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 29 days after administration of monthly ixekizumab).

EXCEPT:

If the Surgical Team deem the procedure to be of especially high infection risk, consider stopping 3-5 half-lives before surger³. 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).

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 ixekizumab 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 ixekizumab in previous 4 weeks.

Exacerbations, or new cases of inflammatory bowel disease have been reported with ixekizumab. If patient presents with abdominal signs and symptoms, consider inflammatory bowel disease as a differential diagnosis and if likely discontinue ixekizumab.

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

For psoriatic arthritis, ankylosing spondylitis and non-radiographic axial spondyloarthritis ixekizumab is typically administered every 4 weeks; however, for plaque psoriasis doses are administered at 0, 2, 4, 6, 8, 10 and 12 weeks then 4 weekly maintenance dosing. Ixekizumab has a half-life of 13 days. 

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), perioperatively, particularly for ixekizumab. 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 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 ixekizumab 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. The British Society for Rheumatology (BSR) guidelines do not include ixekizumab, as it was not approved by NICE at the time, however, their caveat that if surgery is associated with a very high risk of infection consideration should be given to stopping for 3-5 half-lives may still be applicable, 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 bDMARDs can safely be continued before minor surgery². 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 bDMARD 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 disease flare, particularly with medications with a long half-life, such as ixekizumab, 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

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:0.1007/s00393-021-01150-9
   
   
2. 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
   
   
3. Baxter K, Preston CL (eds), Stockley’s Drug Interactions (online) London: Pharmaceutical Press. http://www.medicinescomplete.com [Accessed 6^th February 2024]
   
   
4. Buchbinder, R. Glennon, V. Johnston RV. et al. 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
   
   
5. 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
   
   
6. 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:10.1093/rheumatology/key207
   
   
7. 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]
   
   
8. Joint Formulary Committee. British National Formulary (online) London: BMJ Group and Pharmaceutical Press http://www.medicinescomplete.com [Accessed 6^th February 2024]
   
   
9. 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:10.1016/j.jaad.2018.11.057
   
   
10. Moreira P, Correia A, Cerquerira M, Gil M. Perioperative management of disease-modifying antirheumatic drugs and other immunomodulators. ARP Rheumatol. 2022; 3: 218-224
    
    
11. Pandit, H. & Mankia, K. PERI-operative biologic DMARD management: Stoppage or COntinuation during orthoPaEdic operations: The PERISCOPE trial. Protocol v1.0 (February 2023)
    
    
12. 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
    
    
13. Summary of Product Characteristics – Taltz® (ixekizumab) 80 mg solution for injection in pre-filled pen. Eli Lilly and Company Limited. Accessed via medicines.org.uk 06/02/24 [date of revision of the text May 2023]