Osteonecrosis after intranasal injection with bevacizumab in treating hereditary hemorrhagic telangiectasia: A case report

Abstract

Intranasal bevacizumab injections have been used in treating hereditary hemorrhagic telangiectasia (HHT)-related epistaxis since 2009. It is believed to be a safe and effective treatment for a selected group of HHT patients in reducing frequency and intensity of epistaxis, with few or none adverse effects. In this case report, however, we will describe a patient who developed bilateral osteonecrosis in the knees while undergoing regular intranasal submucosal bevacizumab injections. Although osteonecrosis previously has been documented in patients receiving bevacizumab intravenously in oncologic doses, thus far it has not been reported in patients treated with intranasal submucosal injections. Laryngoscope, 128:593-596, 2018.

Long‐term experience with intranasal bevacizumab therapy

“…In one patient, RISBI was discontinued after 39 months because of a serious systemic adverse event (osteonecrosis) . Additionally, one patient had a very good response after only one treatment, but RISBI was discontinued because the patient moved abroad and was therefore excluded from further calculations.…”

“…As we have described in detail in our recently published case report, one patient developed bilateral osteonecrosis in the knees, assessed as a systemic adverse effect of bevacizumab. 28 This particular patient had received eight doses of 200-mg bevacizumab injected intranasally, with an average interval between treatments of 5.6 months.…”

Intranasal bevacizumab injections improve quality of life in HHT patients

“…First, RISBI can be associated with “therapy resistance” when used in a long‐term context . Secondly, a serious systemic adverse effect (osteonecrosis in the knees) has been reported as a possible rare complication of RISBI . Consequently, we reserve RISBI for patients who are refractory to other therapies.…”

Bevacizumab-associated osteonecrosis of the femur and tibia

“…The association between antiangiogenics and osteonecrosis has been noted in many clinical trials, and the jaw seems to be the classical site of involvement, especially when this drug class is used concurrently with bisphosphonates or corticosteroids [3, 4]. Involvement of the appendicular skeleton appears to be even more uncommon, with only seven cases in adults (Table 1) reported so far, to the best of our knowledge [1, 2, 5, 7, 8]. One of the cases refers to osteonecrosis after intranasal injection with bevacizumab in treating hereditary hemorrhagic telangiectasia [6] A potential negative influence of bevacizumab on the incidence and severity of osteonecrosis of the jaw has been suggested in patients receiving zoledronic acid [9].…”