Age: 51.0
Sex: M
Vaccine: COVID19
Symptoms: Computerised tomogram abdomen, Computerised tomogram pelvis, Echocardiogram, Pulmonary embolism, SARS-CoV-2 test
Clinical narrative: bilateral pulmonary emboli; A PHASE 3 MULTI-CENTER, LONG-TERM EXTENSION STUDY INVESTIGATING THE EFFICACY AND SAFETY OF ABROCITINIB, WITH OR WITHOUT TOPICAL MEDICATIONS, ADMINISTERED TO SUBJECTS AGED 12 YEARS AND OLDER WITH MODERATE TO SEVERE ATOPIC DERMATITIS  This is a report from a Pfizer-Sponsored Interventional Study source. The subject was in the open-label phase of the study at the onset of the event.   A 51-year-old male subject entered study B7451015 on 26Jan2021 and started to receive abrocitinib (lot number 20-002305, expiration date: 30Jun2022) orally (PO), at 200 mg, daily from 29Jan2021 to 10Jun2021 for atopic dermatitis. Most recent dose before the event was 200 mg on 10Jun2021. The subject received suspect concomitant vaccine BNT162B2 (COVID-19 vaccine Pfizer, lot number and expiration date not available) intramuscularly as 1 syringe once for COVID-19 immunization on 09Mar2021 and 29Mar2021 (from somewhere else, not site) both at the age of 51 years old. The study ID of prior study was. Subject's screening visit was on 09Jul2020. His baseline date was on 28Jul2020 and his week 26 visit was on 26Jan2021. Medical history included obstructive sleep apnea from 2018 and ongoing, intertrigo from 29Aug2019 to 2019, sleeve gastrectomy in 2019, tonsillectomy in 1974. It was noted that subject was 69 inches and 292.8 lbs measured in the office on 27May2021. The subject's last body mass index (BMI) as measured at week 12 visit on 27May2021 was 43.2. Subject was a former smoker, stopped in 2000. The subject reported that he was a social drinker, drinking 1-2 drinks during the holiday season for Christmas/New Years. Subject had no known family history of venous thromboembolism/pulmonary embolism (VTE/PE), had no known history of hypertension or malignancy/cancer. Subject did not have any accidental injury, immobility, or recent surgeries. Subject traveled 3-4 times a year and the flights ranged from 3-4 hours at a time. His last flight was in mid May2021. Subject did not have a known reduced mobility reason and he was able to go to parks earlier with his children and walk through the parks. Subject was reported to be sedentary with little to no exercise activities. Concomitant medication included cetyl alcohol/sodium lauryl sulfate/stearyl alcohol (CETAPHIL) for atopic dermatitis from 09Jul2020 and ongoing (most recent dose before the event was on 10Jun2021). On 07Jun2021, the subject experienced bilateral pulmonary emboli which required hospitalization. Clinical course was as follows: The subject had symptoms starting since 07Jun2021 which he believed to be a common cold that he caught from one of his family members. Principal investigator (PI) was notified by the subject on 10Jun2021 at 21:25 that he was experiencing shortness of breath and was on the way to the Emergency Room (ER). When he presented to the ER on 10Jun2021, he was tested for COVID19 since his symptoms included cough, general malaise, and chest pain. COVID19 swab on 10Jun2021 was negative (normal range: low: negative, high: positive). He had a minimally elevated troponin level, troponin I (normal range: high: 0.05 ng/mL) was 0.67 ng/mL on 10Jun2021 and 0.74 ng/mL on 11Jun2021, which was later determined to be due to right heart strain secondary to his pulmonary emboli. On 10Jun2021, the subject had computerized tomogram (CT) angiogram chest that showed bilateral pulmonary emboli (PE), chest x-ray showed normal. On 10Jun2021, portable Anterior-Posterior (AP) Chest X-ray showed prominent upper mediastinum (recommendation for CT evaluation), CT scan with contrast showed extensive bilateral segmental and sub-segmental pulmonary emboli, evidence of right heart strain, few nodular opacities in the lateral segment of right lower lobe that might represent aspiration/small airway disease, ultrasound of lower extremities showed normal and no deep vein thrombosis (DVT) was seen. Subject confirmed with PI on the morning of 11Jun2021 at 07:41 that he was diagnosed with bilateral pulmonary emboli and was admitted. He was initiated on a heparin infusion and then converted to oral apixaban (ELIQUIS) at 5 mg once a day upon discharge and was sent home on 13Jun2021. During his stay, he had a CT abdomen and pelvis with contrast on 12Jun2021 to screen for occult malignancy due to the extent of his pulmonary emboli, the result was normal and no malignancy were seen (no evidence of occult malignancy). He also had a transthoracic echocardiogram performed to evaluate for his cardiac function (report was not released to the site). Other lab test included an echocardiogram which showed normal left ventricular ejection fraction, dilated right ventricle and venous doppler which showed no evidence of deep vein thrombosis. An outpatient colonoscopy had been advised. The action taken with abrocitinib in response to the event was permanently withdrawn on 10Jun2021, for BNT162B2 was not applicable. Subject confirmed that he had stopped taking abrocitinib as instructed. Outcome of the event was recovered on 13Jun2021. The subject returned to site on 15Jul2021 as his final visit/safety follow up and verbally confirmed that his last dose of investigational product (IP) was on 10Jun2021 (subject discontinued his trial participation on 15Jul2021). His IP compliance was calculated as 50 % base on last dose on 10Jun2021. He returned bottles of IP on his final visit on 15Jul2021. He had not undergone any additional treatment or evaluation since being discharged from the hospital. His appointment with his insurance network pulmonologist was scheduled in the following week.   The investigator considered there was a reasonable possibility that the event bilateral pulmonary emboli was related to the study medication abrocitinib and concomitant vaccine BNT162B2 (COVID-19 vaccine Pfizer), but unrelated to other concomitant drug or clinical trial procedure. The investigator commented that as COVID-19 vaccine was relatively new, it was unknown how long the side effects would take to manifest.  Follow-up (22Jun2021): New information reported includes: subject details (study phase the subject was enrolled at the onset of the event), study drug details (dosing regimen, stop date, and action taken for abrocitinib), reaction data (SAE outcome and recovery date, additional clinical course details, and treatment details), and causality assessment of the event with abrocitinib (related), concomitant drug and clinical trial procedure (both unrelated).  Follow-up (28Jun2021): New information reported includes: reaction data (updated SAE term from pulmonary embolus to bilateral pulmonary emboli, event onset date), suspect concomitant vaccine added, medical history added, lab data added, and additional clinical course (subject's symptoms and treatment details).  Follow-up (07Jul2021): New information reported includes: medical history added, lab data added, and additional clinical course (prior study information and subject's details).  Follow-up (15Jul2021): New information reported includes: additional lab tests and clinical course (no additional treatment or evaluation post-discharge, and scheduled appointment).  Follow-up (22Jul2021): New information reported includes: new lab tests were reported and clinical course (subject discontinued his trial participation).  Follow-up (29Jul2021): New information reported includes: study drug detail (lot number and expiration date).  Follow-up (24Aug2021): New information reported includes: lot number and expiration date not available for suspect concomitant vaccine BNT162B2. This follow-up is being submitted to notify that the lot/batch number is not available despite the follow-up attempts made. Follow-up attempts have been completed and no further information is expected.    Follow-up (01Jul2022): This is a Pfizer Sponsored Interventional Study follow-up report. Updated information: dosage information. Study description updated in narrative.; Sender's Comments: The reported event bilateral pulmonary emboli (PT: Pulmonary embolism) is unexpected in the single reference safety document of the investigational product and related per Company assessment.  Based on the current available information, the temporal relationship and lack of conclusive evidence for an alternate etiology, the event of bilateral pulmonary emboli was assessed as related to the study drug abrocitinib. The subject's underlying obesity was a confounding factor. The company considered there was not a reasonable possibility that the event bilateral pulmonary emboli was related to the concomitant vaccine BNT162B2 (COVID-19 vaccine Pfizer). The temporal relationship between the event and BNT162B2 was weak since the event occurred more than two months after the second dose of vaccine. The event was not related to concomitant drugs or clinical trial procedure.   The impact of this report on the benefit/risk profile of the Pfizer product and on the conduct of the study is evaluated as part of Pfizer procedures for safety evaluation, including the review and analysis of aggregate data for adverse events. Any safety concern identified as part of this review, as well as any appropriate action in response, will be promptly notified to Regulatory Authorities, Ethics Committees and Investigators, as appropriate.  The Follow-up information received does not alter the previous company clinical evaluation.