Safety evaluation of ustekinumab for moderate-to-severe ulcerative colitis.

INTRODUCTION: Ustekinumab is a human IgG1 kappa monoclonal antibody that targets the p40 subunit of interleukin (IL)-12 and IL-23 and blocks the binding of these cytokines to the IL-12Rß1 chain of their receptors. Ustekinumab is approved for treating moderate-to-severe ulcerative colitis (UC). AREAS COVERED: We reviewed the mechanism of action, pharmacokinetics, efficacy, and safety of ustekinumab. Future challenges for optimizing UC treatment with ustekinumab are discussed. EXPERT OPINION: Ustekinumab has favorable clinical efficacy and safety profiles for moderately-to-severely active UC. Ustekinumab is the first biologic for targeting IL-12/IL-23 pathways. Therefore, ustekinumab can be a therapeutic option following the failure of other biologics, including anti-tumor necrosis factor-α antagonists and anti-α4ß7 integrin antagonists. However, the positioning of ustekinumab in the therapeutic strategy for UC remains unclear. The efficacy of combinations of ustekinumab and immunomodulators over ustekinumab monotherapy has not been supported in studies. Ustekinumab is a human immunoglobulin G monoclonal antibody with low immunogenicity. Therefore, ustekinumab monotherapy, which should be safe, could be sufficient for treating UC. Further studies are required to understand the efficacy and safety of ustekinumab in patients with UC, particularly in special situations, and to optimize UC treatment with ustekinumab.

Diffuse alveolar hemorrhage associated with ustekinumab treatment.

PURPOSE: A case of diffuse alveolar hemorrhage (DAH) occurring as a reaction to ustekinumab therapy is reported. SUMMARY: After starting ustekinumab for treatment of psoriatric arthritis, a 46-year-old female presented with flu-like symptoms and cough with blood-tinged sputum that had begun 1 week previously. Her initial computed tomography scan of the chest demonstrated bilateral ground-glass opacities. On bronchoscopy, the bronchoalveolar lavage (BAL) return became bloodier from sample 1 to samples 2 and 3. Her BAL fluid was more than 90% hemosiderin-laden macrophages, a finding consistent with DAH. We ruled out infectious etiologies and other common vasculitis conditions that can cause DAH. A diagnosis of ustekinumab-induced DAH was made due to a temporal relationship between initiation of the drug and the patient's presentation and the absence of infection and other alternate diagnosis. Prior case reports including ustekinumab-induced pneumonitis, interstitial lung disease with a granulomatous component, and lupus syndrome have been reported, with this being the first case of DAH in a patient undergoing treatment of psoriatic arthritis. CONCLUSION: A 46-year-old woman developed DAH during ustekinumab treatment. Symptoms abated after drug discontinuation and supportive treament. Clinicians must remain mindful of this rare complication of ustekinumab use in order to avoid potential delays in appropriate DAH treatment.