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Compared with immunomodulators, JAK inhibitors may provide therapeutic advantages with similar rates of adverse events.

The incidence rate assessment of venous thromboembolic events (VTE), serious infections, and malignancies, except for nonmelanoma skin cancer (NMSC), found no significant difference between Janus kinase (JAK) inhibitors and non-JAK agents. The incidence rates for NMSC and major adverse cardiovascular events (MACE) were lower on JAK inhibitors.

Olivia Lamberg, MD candidate, and colleagues gathered and summarized evidence to compare the incidence rate per 100 patient-years (PY) of JAK inhibitors to that of other immunomodulators. They looked at the JAK inhibitors baricitinib, tofacitinib, upadacitinib, ruxolitinib, filgotinib, and the non-JAK agents cyclosporine, methotrexate, etanercept, adalimumab, and prednisone.

As for serious infections, VTE, and malignancies in general, no significant difference in incidence rate was identified between JAK and non-JAK drugs. However, NMSC showed a lower incidence rate in the JAK compared with the non-JAK group: 0.4/100 PY versus 0.6/100 PY (P<0.001).

Significantly lower incidence rates per 100 PY in favor of JAK inhibitors were also detected for MACE with 0.3 versus 0.6 (P<0.001). However, serious and nonserious events of herpes zoster were significantly fewer in the nonJAK 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), 1.1 (15 mg upadacitinib) and 3.1 (100 mg filgotinib), respectively.

In their conclusion, the authors noted a therapeutic advantage in JAK inhibitors with their more precise mechanism of action than the broader-acting immunomodulators based on these valuable insights into the safety profile of JAK inhibitors.

Medical writing support was provided by Karin Drooff, MPH.