Rechallenge With Subcutaneous Mirikizumab After Mild Hypersensitivity Reaction to Intravenous Mirikizumab in a Patient With Ulcerative Colitis and Primary Sclerosing Cholangitis

Background:
The purpose was to investigate if patients can continue subcutaneous injections of mirikizumab after a hypersensitivity reaction to mirikizumab infusions. We report on a patient who developed a hypersensitivity reaction to intravenous (IV) mirikizumab but who was subsequently able to tolerate subcutaneous mirikizumab thereafter. Our patient is a 24-year-old female diagnosed with ulcerative colitis and primary sclerosing cholangitis (PSC) in 2016. She previously trialed the following medications: infliximab (escalated to every 4 weeks with breakthrough symptoms), adalimumab, vedolizumab, ustekinumab, tofacitinib and upadacitinib (nonresponder, elevated LFTs). The patient declined surgical intervention and a decision was made to treat with mirikizumab.
Methods:
Mirikizumab was administered as 300 mg IV infusion over at least 30 minutes at week 0, week 4, and week 8 followed by maintenance injections 200 mg under the skin (given as 2 consecutive injections of 100 mg each) at week 12, and every 4 weeks thereafter. Twenty minutes after completion of her first infusion, the patient developed generalized pruritus and hives on her arms and legs with stable vital signs. She was treated with diphenhydramine 25 mg tab PO x 1 with resolution of symptoms. The patient was premedicated with 25 mg diphenhydramine IV and 4 mg dexamethasone IV prior to her second infusion, without reaction. Patient was given the same premedications prior to the third infusion, and reported developing hives after her infusion was completed which resolved with diphenhydramine 25 mg tab PO x 1. The patient reported clinical response to mirikizumab with less urgency and more formed stools. The mirikizumab package insert states that the injection is a sterile, preservative-free, clear to opalescent, colorless to slightly yellow to slightly brown solution for intravenous infusion or subcutaneous injection. Inactive ingredients include trisodium citrate dihydrate, anhydrous citric acid, sodium chloride, polysorbate 80, and water. The patient was discussed with Allergy who advised that given the history, there was low likelihood of a true IgE-mediated allergy to mirikizumab. The allergist recommended to take 2 cetirizine 10 mg tablets the night before and morning of mirikizumab maintenance injections to prevent a reaction.
Results:
Our patient has since been able to tolerate 3 maintenance injections with no reported reactions by implementing this premedication method. She is continuing to tolerate and respond to mirikizumab maintenance injections. Fecal calprotectin has decreased from 224 mcg/g to 109 mcg/g 4 months after mirikizumab initiation.
Conclusions:
We report a case where rechallenge with subcutaneous mirikizumab proved to be successful after a mild hypersensitivity infusion reaction to IV mirikizumab. After careful consideration, we believe subcutaneous mirikizumab should not be ruled out as a treatment option for subsequent administrations after initial mild mirikizumab infusion-related reaction.