Notes

This is a report from a Pfizer Sponsored Interventional Study source for Protocol A3921133, Center ID/ Subject ID 12441008. A 51-year-old Hispanic female subject started to receive tofacitinb citrate, tablet (Lot # 41002017, expiration date: 30Sep2016; Lot# 41097694) orally 10mg twice daily from 21Jul2015 to 19May2016 and from 13Jun2016 to 19Jul2016 for the study indication rheumatoid arthritis. The most recent dose before the event was reported as 10mg. By last it was reported that subject received 1468 tablets of tofacitinib during study (counting from the randomization visit to the last count in visit No 6 on 21Jul2016) and it was reported that there was not any deviation to the protocol. Concomitant suspect medications included methotrexate, tablet orally 20mg weekly from 05Jul2016 to 07Feb2017 and orally after since 14Mar2017 and ongoing at 20 mg weekly for rheumatoid arthritis; and prednisolone orally 5mg daily since Jun2014 for rheumatoid arthritis.

The subject's medical history included right cataract surgery on 16Jan2013, hypertension from Feb2014 and ongoing, anemic syndrome from Jan1992 and ongoing and left eye cataract from unspecified date to ongoing. Other concomitant medications included folic acid orally 1mg daily since Nov2013 and ongoing for prevention for use methotrexate, losartan orally 50mg daily since 20Feb2014 to 19May2016 for hypertension, losartan orally 50mg twice day since 20May2016 to ongoing for hypertension, ferrous sulfate orally 300 mg daily since Apr2016 and ongoing for anemic syndrome, calcium carbonate/ colecalciferol (CALCIUM CARBONATE AND VITAMIN D3) orally at 1 dosage form (600 mg/ 200 IU) daily since Jun2014 and ongoing for osteoporosis prevention and omeprazole orally 20 mg daily since 12Jun2016 and ongoing for gastric prevention. Subject also took paracetamol (ACETAMINOPHEN) oral 1000 mg twice day since Nov2016 and ongoing for pain secondary rheumatoid arthritis.

Serious adverse event (SAE) was reported post-herpetic keratitis right eye in Sep2016 with serious criterion of disability. It was reported that considered the 8.6 numeral of protocol, the significant and persistent visual disability, substantial disruption of their ability to lead a normal life and the depressive state that the subject was suffering, it was concluded that the herpetic keratitis is a SAE because its evolution have been with sequelae of ulceration and as a final result a scar (leucoma) stablishing the visual acuity loss. The subject will require a corneal transplant in a long term. By now it was proposed an amniotic membrane coating on right eye corneal to avoid new ulceration episodes. Summary from the site reported that first of all the subject presented a SAE (Herpetic meningoencephalitis) since 19May2016 until 11Jun2016 codified in case number 2016291136, this event was treated in hospital and after discharge, she was attended in specialists office by external appointments. The diagnosis was meningoencephalitis secondary to facial and ocular herpes zoster infection, corneal ulcer on right eye. The herpes zoster infection generated meningoencephalitis and at the same time it affected 1st branch of the V cranial pair which ended affecting the right eye. On 21Oct2016 subject was seen by ophtlamology reporting that subject has a right metaherpetic corneal ulcer and it is still pending a cataract surgery on left eye. It was reported that there was not herpes simplex, it was the herpes zoster previously described (Information is presented as received by the investigator). By last it was indicated that keratitis was treated initially in hospitalization and after it was attended in specialists office by external appointments with acyclovir 800mg/TID during 10 days. Upon follow-up received on 27Jul2017, it was reported that the event did not recur when subject re-started administration of methotrexate (Information is presented as received by the reporter). It was reported that the subject attended her scheduled visit No 10 (month 24) on 26Jul2017 and she referred not having reaction of arthritis and she continued with moisturizing treatment for right eye with no new episodes of keratitis, however it remains pending the evaluation by ophthalmology.