Medicines

Biologics and respiratory complications: no overt PE risk with TK inhibitors


Respiratory physicians asked for their take on the possible pulmonary side effects of small molecule tyrosine kinase inhibitors (TKIs) can reassure their colleagues.

According to a meta-analysis of all published trial data on adverse events, there is some signal for infections but none for an increased risk of pulmonary embolism (PE).

The findings are timely, coming on the back of a recent Pfizer announcement about transitioning patients in a post-marketing study of tofacitinib for rheumatoid arthritis from 10 mg twice daily to 5 mg twice daily.

As reported in the limbic in February, the dose change was in response to the higher occurrence of PE in patients on the higher dose compared to patients treated with an anti-TNF.

There was also increased mortality in patients on 10mg of tofacitinib compared to 5mg – the FDA approved dose for adults with moderate to severe rheumatoid arthritis.

Speaking in the Late Breaking Abstract session at TSANZSRS, Dr Jun Keng (JK) Khoo said the long-term safety and class effects of the TKIs were largely unknown.

The meta-analysis comprised more than 153,000 participants across 75 studies, mostly randomised controlled trials with a median duration of 24 weeks.

It found there was a low but significantly increased risk of developing upper respiratory tract infections, pneumonia and influenza with exposure to TKIs compared to placebo or other therapies.

Longer observational studies showed a low incidence of all respiratory adverse effects comparable to anti-TNFs.

And there was no significantly increased risk for other respiratory complications including thrombosis/PE, drug-induced ILD or lung neoplasms. The incidence of PE was estimated at 0.2-1.2%.

Dr Khoo, from Alfred Health in Victoria, said there was a need for longer-term real world data to further characterise any pulmonary toxicity from the drugs.

He told the limbic that patients should be managed no differently from those starting other biologic therapy.

“I would view it the same as starting those people on any biologic or any immunosuppressive therapy. You make sure they are vaccinated, you screen for latent infections and if they are positive you treat them.”

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