Swedish study finds no increased risk for most – but not all – malignancies in patients on JAK inhibitors vs TNF inhibitors.
A large Swedish cohort study has found patients with rheumatoid arthritis and psoriatic arthritis on JAK inhibitors are no more likely than their peers on TNF inhibitors to develop most cancers, with non-melanoma skin cancer being the exception.
Published in Annals of the Rheumatic Diseases, the observational study followed over 10,000 Swedish nationals with RA and almost 4500 with PsA and no history of cancer.
Most of the RA group (over 7000 patients) were on TNFi therapy, with around 3500 on non-TNFi bDMARDs (rituximab, abatacept, tocilizumab, sarilumab) and almost 2000 on JAKi therapy – either tofacitinib, baricitinib or upadacitinib. (Patients who switched treatments over the study period were included in the data for each treatment and are therefore counted more than once.)
In the PsA group, the vast majority were on TNF inhibitors, with only 379 patients on JAK inhibitors and 185 in the non-TNFi biologics cohort.
Data were collected from 2016 (2017 for JAKi) to the end of 2020. Given that JAKi is still a relatively recent therapy in Sweden, the median follow-up time from initiation was just under two years, making the results only relevant in terms of short-term risk.
Overall, the researchers found that incidences of different cancers were relatively similar across the different study arms, with the exception of non-melanoma skin cancer (NMSC).
RA patients on JAK inhibitors were at increased risk of skin cancers, with 59 incident NMSC events in the JAKi cohort, 126 in the non-TNFi cohort and 189 in the TNFi cohort. This corresponded to a fully adjusted HR of 1.39 (95% CI 1.01 to 1.91) for JAKi versus TNFi. There was no difference in risk between those on TNFi vs non-TNFi biologics.
For cancers other than NMSC, the overall HR was 0.94 (95% CI 0.65 to 1.38).
A subset of the RA patients had cardiovascular risk factors, allowing some comparison with the ORAL Surveillance cohort, although other restrictions, such as disease activity and concomitant csDMARDs, were not met. In this group, the incidence of cancer increased in both JAKi and TNFi groups, but the hazard ratio remained the same as in the main analysis.
Among patients with PsA, the researchers identified a potential signal for increased cancer risk in those taking JAKi vs those on TNFi, with numbers suggesting around double the risk for NMSC and also for cancers excluding NMSC. However, the low incidence rates didn’t allow meaningful interpretation.
Across all groups, the incidence of NMSC was higher than in the general population.
The ORAL Surveillance study raised a red flag about JAK inhibitors and malignancies, with a statistically significant 50% higher risk of cancers excluding NMSC for tofacitinib vs TNF blockers, while for NMSC there was double the risk in the tofacitinib groups vs TNFi.
However, like the current study, other real-world evidence cohorts, such as Corrona-RA and STAR-RA, found no increased risk of non-NMSC malignancies.
It’s still unclear exactly why RA patients on JAK inhibitors are at higher risk of skin cancer and a causative biological mechanism has not been determined.
The researchers called for the risk to be viewed in light of the elevated risks for adverse outcomes for patients with RA, particularly among those with no other effective treatment option.
