JAKis don’t beat TNFis in high-risk patients

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Anti-JAKs are not associated with cancer, and other highlights from the EULAR session: There is still a lot to SAY about biologicals for RA!

The EULAR session, “There is still a lot to SAY about biologicals for RA!” held on day 2 of the congress featured research on anti-JAK effectiveness in patients at higher risk of adverse events. 

Other highlights included a South Korean real-world study of JAKi safety and a long-term follow up of a planned disease activity-guided dose optimisation tapering program — the DRESS study. 

What if anti-JAKs were more effective than TNFi in high-risk patients? 

In April, Australia’s TGA followed the lead of the FDA and European Medicines Agency by slapping a black box warning on anti-JAK medicines tofacitinib (Xeljanz, Pfizer), upadacitinib (Rinvoq, AbbVie) and baricitinib (Olumiant, Lilly). 

The warning states that the drugs should only be used as a last resort for patients with a history of atherosclerotic cardiovascular disease or other cardiovascular risk factors (such as current or past long-time smokers)​, with malignancy risk factors (such as current malignancy or history of malignancy) ​or who are 65 years of age and older. 

Now there are questions as to whether those same patient groups also have the most to gain from JAKi therapies.  

Speaking at a biologics-focused oral abstract session at EULAR 2023, Karolinska Institutet researcher Dr Hannah Bower went some way to answering that.  

“We were interested in asking the question ‘were JAKis performing better than TNFi in all risk groups, and does the relative effectiveness differ within sex, different age groups and different cardiovascular risk groups,” she said. 

Dr Bower presented results from a study which utilised data from the Swedish Rheumatology Quality register entered between 2016 and 2021. 

Of the 16,207 participants with RA whose data was included, more than half were on TNFIs, around 15% were on JAKis and the remaining 30% were on non-TNFi bDMARDs.  

While JAKis were found to have an overall superior effectiveness in terms of response of six months compared to TNFis – in both individuals with and without cardiovascular or age-related risk factors – the researchers did not find a major modification effect.  

“In other words, the relative effectiveness of JAKis versus TNFIs are not statistically significantly different within levels of age, cardiovascular risk or smoking groups,” Dr Bower told EULAR delegates.  

“To answer our question, we did not find any evidence that JAKis were performing better or worse where safety concerns are the highest.”  

  • OP0133 – Do JAKis work the best among those RA patients where their safety concerns are the highest? (DOI: 10.1136/annrheumdis-2023-eular.346) 

Cancer and CVD outcomes in RA patients: a South Korean registry study 

Ever since the ORAL Surveillance study raised a red flag around JAK inhibitors and malignancies and CVD outcomes – seemingly contradicted by real-world evidence – controversy has swirled around the drug class.  

Speaking at the same Thursday morning session at EULAR, South Korean researcher Professor Sung Soo Ahn added to the growing body of evidence backing the JAKi safety profile.  

Professor Ahn’s research drew data from a South Korean government health insurance review and assessment database.  

Only patients with seropositive RA who were over the age of 18 were included, with a total pool of around 102,000 patients analysed for cancer outcomes and around 96,000 for CVD outcomes, including deep vein thrombosis, pulmonary embolism and composite cardiovascular events. 

“Our analysis showed that the incidence rate ratio was increased in patients that have treated with JAK inhibitors and biologics compared to those who were only treated with csDMARDs in regards to skin, lung, liver and prostate cancers,” he told delegates.  

However, other than the higher incidence of the four site-specific cancers, neither JAKi nor biologic use was associated with a higher incidence of cancer overall.  

There was also no difference in CVD outcomes among the different treatments. 

While the results were reassuring overall, Professor Ahn said that the increased incidence of the site-specific cancers did need further investigation.  

  • OP0132 – Cancers and cardiovascular diseases in patients with seropositive rheumatoid arthritis treated with JAK inhibitors and biologics (DOI: 10.1136/annrheumdis-2023-eular.1) 

Long-term effectiveness of the DRESS tapering program 

Discontinuing TNF inhibitors as part of a planned disease activity-guided dose optimisation tapering program can be safe and even allow for drug-free remission for some patients, according to an abstract presented by Dutch rheumatologist Dr Noortje van Herwaarden.  

Dr van Herwaarden, who was involved in the original Dose Reduction Strategy of Subcutaneous TNFi (DRESS) study, revisited the now decade-old study cohort to assess the long-term effectiveness of the tapering strategy in rheumatoid arthritis patients. 

“[The protocol] is about reducing the dose or lengthening the [between-dose] interval up to a stopping attempt,” she told EULAR delegates.  

“And what is important is to measure disease activity and … it’s important to increase the dose when disease activity increases above [a given] threshold.  

The treat-to-target strategy has been studied extensively over the last few years, but there’s a scarcity of long-term data.  

The researchers were able to access data for 170 of the original 180 DRESS patient cohort, out of which 161 (95%) attempted at least one dose reduction and 119 (70%) were able to taper to full discontinuation.  

The median number of reduction attempts per patient was two, with a maximum of four.  

On their first attempt at discontinuation, patients were able to stay off TNFis for a median of seven months. 

A total of 25 (15%) patients never had to restart TNFis or another bDMARD throughout the study, essentially meaning they remained in remission or very low disease activity. 

In conclusion, Dr van Herwaarden said, tapering can yield stable low disease activity over time without causing long-term disease deterioration. 

  • OP0131 – Disease activity-guided dose optimization including discontinuation of TNF-inhibitors in rheumatoid arthritis is effective for up to 10 years: results of the DRESS study (DOI: 10.1136/annrheumdis-2023-eular.3732) 

The EULAR 2023 Congress took place in Milan, Italy, from 31 May to 3 June.  

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