Pregnancy Outcomes in the Tofacitinib Safety Databases for Rheumatoid Arthritis and Psoriasis.
Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA), and is being investigated for the treatment of psoriasis. Both conditions can present in women of child-bearing potential, but pregnancy was an exclusion and discontinuation criterion in tofacitinib randomized controlled trials (RCTs) because of the unknown effects of tofacitinib on mother and child. Tofacitinib is a small molecule that has the potential to cross the placenta.



The objective was to report outcomes of pregnancy cases identified through April 2014 from tofacitinib RA/psoriasis RCTs, RA post-approval non-interventional studies, and spontaneous adverse-event reporting.



Pregnancy outcomes were categorized as follows: healthy newborn, medical termination, fetal death, congenital malformation, spontaneous abortion, or pending/lost to follow-up.



Out of 9815 patients, 1821 female patients of child-bearing age were enrolled in the RA/psoriasis RCTs; 47 women became pregnant, including 33 who received tofacitinib monotherapy, 13 who received combination therapy with methotrexate (RA patients only), and one patient whose therapy was still blinded. No fetal deaths were reported. One congenital pulmonary valve stenosis (monotherapy, n = 1), seven spontaneous abortions (monotherapy, n = 4; combination therapy, n = 3), and eight medical terminations (monotherapy, n = 4; combination therapy, n = 3; blinded therapy, n = 1) were identified. Remaining cases reported healthy newborns (n = 25) or were pending/lost to follow-up (n = 6). Forty-four cases of paternal exposure to tofacitinib were reported (monotherapy, n = 43; combination therapy, n = 1), including five spontaneous abortions (monotherapy, n = 4; combination therapy, n = 1), 23 healthy newborns, and 16 pending/lost to follow-up.



The pregnancy outcomes reported in this small number of RA/psoriasis patients appear similar to those observed in the general population and in patients treated with biologic therapies for inflammatory diseases. However, definitive conclusions cannot be drawn, and pregnancy outcomes in patients receiving tofacitinib will continue to be monitored.
Duke University School of Medicine, Durham, NC, USA.
Megan E B
ME
Clowse
Department of Dermatology, Wake Forest University School of Medicine, Winston-Salem, NC, USA.
Steven R
SR
Feldman
The NIHR Newcastle Biomedical Research Centre, Newcastle University and Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK.
John D
JD
Isaacs
Department of Dermatology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Alexandra B
AB
Kimball
Division of Immunology/Rheumatology, Stanford University School of Medicine, Palo Alto, CA, USA.
Vibeke
V
Strand
Dermatology Centre, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK.
Richard B
RB
Warren
Hospital General de Cuernavaca, Cuernavaca, Morelos, Mexico.
Daniel
D
Xibillé
Pfizer Inc, 500 Arcola Rd, Collegeville, PA, 19426, USA.
Yan
Y
Chen
Pfizer Inc, Groton, CT, USA.
Donald
D
Frazier
Pfizer Inc, New York, NY, USA.
Jamie
J
Geier
Pfizer Inc, Groton, CT, USA.
James
J
Proulx
Pfizer Inc, 500 Arcola Rd, Collegeville, PA, 19426, USA. Amy.marren@pfizer.com.
Amy
A
Marren
D000328:Adult; D018501:Antirheumatic Agents / Q000008:administration & dosage / Q000009:adverse effects; D001172:Arthritis, Rheumatoid / Q000150:complications / Q000188:drug therapy*; D016208:Databases, Factual; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007231:Infant, Newborn; D008727:Methotrexate / Q000008:administration & dosage; D010880:Piperidines / Q000008:administration & dosage* / Q000009:adverse effects; D011247:Pregnancy; D011256:Pregnancy Outcome; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects; D011565:Psoriasis / Q000150:complications / Q000188:drug therapy*; D011743:Pyrimidines / Q000008:administration & dosage* / Q000009:adverse effects; D011758:Pyrroles / Q000008:administration & dosage* / Q000009:adverse effects; D016032:Randomized Controlled Trials as Topic; D055815:Young Adult
D018501:Antirheumatic Agents; D010880:Piperidines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D011758:Pyrroles; C479163:tofacitinib; D008727:Methotrexate