International JAK-POT collaboration has provided data from 13 international registers (Europe and Quebec) in order to assess the risk of cancer in subjects with rheumatoid arthritis (PR), treated by Jaki versus Biomedicaments (anti-TNF or other biotherapies) (1).
Jaki and cancers, rather reassuring data
The analysis was made from the initiation of treatment up to five years after the judgment, or until the beginning of a new treatment, until death or until the loss of follow -up if necessary. Of the 53,169 treatment initiations in 33,127 patients, 219 non -melanocytic skin cancer and 638 other cancers were reported. The gross incidence of cancers to the exclusion of skin cancers was lower for anti-TNF (2.2/1,000 PR pr) than JAKI (2.9/1,000 PR PA patients) and other biotherapies (3.1/1000). However, a more in-depth statistical analysis has not revealed any significant difference in the impact of these two types of cancer between Jaki and Anti-TNF, nor between Jaki and other biologicals. The so -called high -risk population (patients aged 50 and over having at least one cardiovascular risk factor) represented approximately 39.4 % of therapeutic sequences. In this subgroup, the risk of cancer was higher: 3.2; 4.2 and 4.1 per 1,000 patients-year-olds for anti-TNFs, jaki and other biotherapies. However, as for the general population, there was no significant difference in the incidence of cancers between jaki and other drugs. Other analyzes are provided, including the inclusion of additional registers in order to improve statistical power and the evaluation of the incidence on different exposure periods.
Towards regular dermatological monitoring?
A Swedish cohort study (SRQ register) has more specifically evaluated the risk of overall skin cancer and by subtype in PR patients having started treatment with anti-TNF, another biotherapy (slaughter, anti-IL6 r, anti-CD20) or by JAKI between January 1, 2012 and December 31, 2021 (2). The data was crossed with the national cancer register. It also assessed the risk of second skin cancer in patients with history of skin cancer and starting targeted therapy.
In total, 21,121 PR patients were identified: 2,300 with initiation of a jaki, 6,316 with initiations of a non-anti-TNF biomedicism and 12,502 with an anti-TNF. The median duration of jaki treatment was 2.5 years (1.2-3.5), 5.1 years for non-anti-TNF biotherapies (2.8-7.3) and 4.7 for anti-TNF (2.5-7,2). 94 skin cancers were identified under Jaki, 407 under biological non-TNF and 628 under anti-TNF.
Compared to anti-TNF treatment, a significant sparrow-in-skin cancer was observed under Jaki with an HR of 1.72 (95 % CI: 1.02–2.87) and 0.81 (95 % CI: 0.60-1.07) for non-anti-TNF biotherapies. This surgery mainly concerned the basalcular carcinomas. In patients with history of skin cancer, the risk of recurrence is also higher under Jaki with an HR of 2.76 (1.02-7.44) versus anti-TNF and an HR of 1.54 (0.79-3.02) under non-anti-TNF biological treatment.
Thus, compared to anti-TNFs, Jaki are associated with an almost doubled risk of skin cancer in PR patients and the risk of recurrence also appears two to three times higher.
For the authors, the results justify the implementation of regular dermatological monitoring in Jaki patients.
Cardiovascular effects counterbalanced by the analogues of GLP-1
Finally, concerning the cardiovascular risk (CV) inherent in the Jaki, a retrospective cohort analysis was carried out using the Trinetx platform in order to compare the cardiovascular accidents observed in patients with treated by JAK inhibitors, with and without analogues of GLP-1 (3). After pairing by propensity score, each cohort included 2,449 patients followed for five years. For the acute coronary syndromes, patients in the similar GLP-1 group presented a significantly lower risk (RR = 0.645). The same is true for all arterial cardiovascular events (RR = 0.673). Regarding deep vein thrombosis, the risk is also significantly reduced (RR = 0.69). Although the similar group of GLP-1 has shown a downward trend in the risk of stroke and peripheral arterial thrombotic accidents, the difference was not significant.
These data reinforce the potential interest of AGLP-1 to reduce certain cardiovascular risks in patients with rheumatoid arthritis and treated by Jaki. However, not all effects were significant and additional studies are necessary to validate these results.
(1) Aymon R et al. OP0232
(2) Huss v et al. On 0067
(3) Beltagy A. OP 0069
