JAK inhibitors have similar incidence rates of long-term adverse events as traditional immunomodulators

For venous thromboembolic (VTE) events, serious infections, and malignancies, except for non-melanoma skin cancer (NMSC), no significant differences in incidence rates of long-term adverse events were detected during treatment with JAK inhibitors versus non-JAK agents. The only observed disadvantage of the JAK inhibitors was a significantly higher incidence rate of herpes zoster infections. Yet, the incidence rates for NMSC and major adverse cardiovascular events (MACE) were lower on JAK inhibitors.

In the advent of the broadening successful use of JAK inhibitors in dermatology, there is notable interest in potential new indications that could benefit from this class of drugs [1]. In this context, the question of long-term safety is an important topic and a black box warning for long-term adverse events by the FDA has led to concerns. To gain further insight, Ms Olivia Lamberg (University of Michigan, MI, USA) and colleagues gathered and summarised evidence to compare the incidence rates of adverse events per 100 patient-years (PY) of JAK inhibitor use versus other immunomodulators. They looked at the JAK inhibitors baricitinib, tofacitinib, upadacitinib, ruxolitinib, and filgotinib, and non-JAK agents cyclosporine, methotrexate, etanercept, adalimumab, and prednisone.

For serious infections, VTE, and malignancies in general, no significant difference in incidence rates was identified between JAK and non-JAK drugs. However, NMSC showed a lower incidence rate in the JAK group compared with the non-JAK group: 0.4/100 PY versus 0.6/100 PY (P<0.0001). Significantly lower incidence rates per 100 PY in favour of JAK inhibitors were also detected for MACE with 0.3 versus 0.6 (P<0.0001). However, serious and non-serious events of herpes zoster were significantly fewer in the non-JAK category (3/100 PY vs 0.5/100 PY; P<0.001).

The research also included results for single agents and different daily dosages. Depending on these variations, the meta-analyses and single study estimates for malignancies (incidence rate/100 PY) on JAK inhibitors ranged from 0 (baricitinib) to 0.9 (tofacitinib). Corresponding findings for MACE, VTE, and serious infections were, for example, 0 (15–20 mg ruxolitinib) and 0.5 (5 mg tofacitinib), 0 (30 mg upadacitinib) and 0.5 (4 mg baricitinib), and 1.1 (15 mg upadacitinib) and 3.1 (100 mg filgotinib), respectively.

In their conclusion, the authors mention a therapeutic advantage of JAK inhibitors with their more precise mechanism of action than the broader-acting immunomodulators and consider it safe to use JAK inhibitors, based on these valuable insights into the safety profile.

Relevant reading:

• Cardiovascular safety of JAK inhibitors: reassuring results from a real-world study (EULAR 2023)

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   1. Lamberg O, et al. Long-term adverse event risks of systemic Janus kinase (JAK) inhibitors versus traditional immunomodulators. P53329, 2024 AAD Annual Meeting, 8–12 March, San Diego, USA.

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Posted on 22 April 20241 May 2024