What are the common side effects of JAK2 inhibitors?

What are the common side effects of JAK2 inhibitors and how can they be managed?

Like most medications, the JAK2 inhibitors do come with some side effects. In truth, in my patient panel, the majority of patients derive benefit from these therapies without many side effects at all, and are willing to tolerate any potential risk for the side effects. But there are some that do have side effects.

The main side effect that I tell my patients about with JAK inhibitors is the fact that the blood counts may be suppressed, particularly with some of the older therapies, such as ruxolitinib and fedratinib. Their hemoglobin may decrease and their platelets may decrease. This is a dose-dependent phenomenon. And therefore, if we see these laboratory abnormalities after starting the therapy, we can change the dose and we can decrease the JAK2 inhibitor dose for this patient, as long as they're still deriving benefit in the other aspects, such as splenomegaly and symptom response.

Outside of the laboratory abnormalities, we do see a number of other potential complications. The JAK2 inhibitors may be mildly immunosuppressive, and we may see reactivation of certain infections, shingles being the predominant infection. And I do try to tell my patients that it's a good idea to be vaccinated for the shingles virus prior to starting JAK2 inhibitors.

Other aspects for patients' health that we consider are skin exams. These JAK2 inhibitors do portend an increased risk for non-melanoma skin cancers. So I recommend that patients receive an annual skin exam by their primary care doctor or dermatologists. We check patients' lipid levels in case of increased lipids and cholesterol that could happen from the JAK inhibitors in general.

And there are a number of specific side effects associated with each specific JAK2 inhibitor. For fedratinib, we would want to make sure that patients are checked and repeated for nutritional deficiencies, specifically thiamine, to avoid neurologic dysfunction. That has been seen in some of the fedratinib clinical trials.

Due to the specific targeting of pacritinib and momelotinib, some of these patients may experience diarrhea. So we try to tell patients that if they do experience a large amount of stool burden, we can consider loperamide even as prophylaxis before they start taking these niche JAK2 inhibitors.