Dr Claire Barrett

A comprehensive review of infection risk in patients on targeted and biologic therapies for rheumatoid or psoriatic arthritis has reinforced the complexity of attributing risk to specific agents.

The review, published in Annals of the Rheumatic Diseases, notes that RA and PsA per se are associated with an increased infectious risk and highlights the additional contribution of individual risk factors, comorbidities and previous therapies.

“For all the licensed targeted therapies, this slight increased risk is acceptable regarding the risk of an alternative treatment, usually higher doses of steroids or classical immunosuppressive drugs like methotrexate or hydroxychloroquine,” the review authors said.

“Steroids, besides increasing the risk of diabetes, cardiovascular events, osteoporosis, also increase the risk of infections even given at a very low daily dose of 5mg/day.”

“Thus, the infectious risk of any new targeted drug has to be analysed regarding what would be the infectious risk of pursuing or increasing steroids rather than giving this new targeted drug.”

The review recommended screening for infections such as TB and hepatitis B, and age-appropriate vaccinations for Streptococcus pneumoniae, influenza and other pathogens, before commencing TNF inhibitors.

It also recommends their discontinuation in the event of serious infection .

Regarding the use of other biologics, recommendations and comments included:

• IL-6-targeting agents: screening for latent TB infection should be performed although there was a lower risk than with TNFs; diagnosis of infectious episodes during therapy may be hindered due to the suppression of CRP synthesis.
• IL-17-targeting agents: associated with a dose-dependent increased risk of mucocutaneous candidiasis, usually in the form of oral or vulvovaginal candidiasis.
• JAK inhibitors: increase the risk of herpes zoster esp in patients ≥65 years and those receiving concomitant corticosteroid therapy. Antiviral prophylaxis with (val)aciclovir may be individually considered in patients with multiple risk factors.
• CD20 antagonist: rituximab-induced HGG may increase susceptibility to capsulated bacteria. Age-appropriate vaccinations for S. pneumoniae, Haemophilus influenzae type B and influenza advised. Screening for chronic HBV infection before starting therapy; antiviral prophylaxis while on therapy and for at least 12–18 months after the last dose for HBsAg-positive patients; monitoring for HBV reactivation for at least 12 months after post-prophylaxis. Prophylaxis (usually with lamivudine) for HBsAg-negative/anti-HBc-positive patients to prevent reactivation of resolved HBV infection.

Commenting on the review, Dr Claire Barrett told the limbic that COVID-19 had brought anxieties about infection to the fore and resulted in some patients stopping their medications.

“One thing we know for sure is that uncontrolled disease is associated with greater risk of infection. And it’s not just patients but some doctors e.g. GPs who underestimate the risk of uncontrolled inflammatory disease,” she said.

“COVID has reinforced our belief that the best way to look after a patient is to find the medication that controls their disease.”

She said the consistent message from the ARA, Arthritis Australia and other organisations in 2020 had been to emphasise to patients that the risks of not taking their medications were substantial.

And the same applied outside COVID-19.

“Whether the initial DMARD treatment was hydroxychloroquine, methotrexate or sulfasalazine, patients are only eligible to commence on biologics because they have severe active disease, and severe disease itself is associated with risk of infection.”

She noted that despite risk stratifying patients – e.g. older age, diabetes, renal impairment, steroid treatment – there were still some patients with no risk factors who would get recurrent infections.

Dr Barrett, a rheumatologist in Redcliffe in Queensland, senior lecturer at the University of Queensland and vice president of the ARA, said – as per the review – that abatacept seems to be better tolerated with respect to infection risk than some other targeted therapies.

“We are all cautious about the Janus kinase inhibitors because of herpes zoster and there may be a game changer when we get an attenuated vaccine but at the moment the only vaccine funded in Australia is the live vaccine.”

“The decision to start a targeted therapy is always going to be a conversation between the rheumatology team and the patient.”

She added that rheumatologists were quite willing to consult with colleagues such as hepatologists, respiratory physicians or infectious diseases specialists to assist in the management of patients with specific infection risks.