An Australian expert group has developed pre-therapy and vaccination screening guidance in a bid to ward off the unique complications associated with the use of advanced treatments for IBD. 

In a paper published in Alimentary Pharmacology & Therapeutics, Professor Rupert Leong, gastroenterologist and professor of medicine at University of Sydney and Macquarie University, and colleagues say ‘expanded risk mitigation strategies are essential’ given the increasingly complex IBD therapeutic landscape.  

The group, involving 19 gastroenterologists and consumer representatives, argue that it’s time to modify established screening guidelines because of the unique adverse effect profiles tied to advanced IBD treatment classes.

Beyond that, the group warn that given the immunosuppressive effects of advanced therapies, an ageing IBD population and global pandemics, reviewing infections and their vaccinations should be a priority – particularly for COVID-19, respiratory syncytial virus (RSV), pneumococcal and human papillomavirus (HPV) among others. 

The guidance, made up of six consensus statements, looks at assessment procedures and vaccinations before starting monoclonal antibodies, Janus kinase (JAK) inhibitors or sphingosine-1-phosphate (S1P) modulators for IBD. 

While vedolizumab, ustekinumab and the IL-23 inhibitors risankizumab and mirikizumab have favourable safety profiles with lower risks of infection and malignancy, other advanced agents carry greater risk of complex treatment complication, the group explains. 

The JAK inhibitors filgotinib, tofacitinib and upadacitinib have the potential to induce infections, malignancy, major adverse cardiac events (MACE) and thrombosis, while TNF inhibitors increase the risk of infections and related hospitalisations, the group notes. For S1P-modulators, ozanimod and etrasimod, hypertension, bradycardia and macular oedema are concerns. 

Consensus for agreement was achieved for six of eight statements. The panel unanimously disagreed with the statement that patients under consideration for advanced therapy should have John Cunningham (JC) virus serology universally performed.  

Meanwhile, the statement that patients under consideration for JAKi should undergo creatine kinase (CK) level testing prior to commencement, was met with mixed response – while none of the group strongly agreed or strongly disagreed with the statement, 26% agreed, 37% disagreed and 37% remained neutral, meaning the statement was rejected.  

The group’s evidence review revealed that, while CK elevation was a frequent laboratory abnormality reported in patients with UC treated with tofacitinib (12.3%), there was no significant clinical weakness, muscle pain and rhabdomyolysis.   

“In the absence of clinical significance and the lack of specificity, the need for CK universal testing and follow-up was deemed unnecessary by the consensus group. However, CK testing is required in those that develop muscle pain,” the group maintains. 

The remaining six statements received agreement by 80% or more of the group. 

The most strongly agreed statement, with ‘strong agreement’ from all panel members, recommends that vaccination should be undertaken for VZV, influenza, COVID-19 and pneumococcal and human papillomavirus (HPV) (if < 26 years old, or ≥ 26 with risk factors).  

Patients with IBD on systemic immunosuppressive therapy are more susceptible to VZV reactivation and may develop a more severe disease course from viral reactivation, the panel said.  

Among the risk factors for reactivation is older age, Asian ethnicity and those on corticosteroids, TNFi, JAK inhibitors and S1P modulators. What’s more, comorbidities such as rheumatoid arthritis, active haematological malignancies and monogenic IBD germline mutations also pose increased risk, they warn.  

“The recombinant VZV vaccine (Shingrix) is ideal in patients soon to commence or already on advanced therapies,” they advised. 

Elsewhere, the group says evidence supports both the COVID-19 vaccination in IBD, as well as the provision of additional vaccine doses for subgroups of suboptimal vaccination response such as in patients with uncontrolled disease activity and corticosteroid use. 

“Immunosuppressed IBD patients that develop symptomatic COVID-19 infection should be considered for early antiviral therapy irrespective of prior vaccination status,” they also note. 

Also receiving universal agreement from the panel is the recommendation that doctors order fasting lipid profile, cardiovascular and venous thromboembolism (VTE) risk assessment and age-appropriate cancer screening in addition to full blood count, renal and liver function tests prior to commencement.  

You can view the full list of recommendations here.