Contributions
Abstract: P749
Type: Poster
Abstract Category: Therapy - disease modifying - 29 Risk management for disease modifying treatments
Background: Alemtuzumab is approved in >60 countries for the treatment of RRMS. Although alemtuzumab is low/undetectable in serum within 30 days of IV administration, women of childbearing potential are advised to use effective contraception for 4 months (mo) after treatment. Murine studies show no alemtuzumab-related teratogenicity, but no controlled human clinical studies of alemtuzumab in pregnancy exist.
Goal: Provide updated pregnancy outcomes in alemtuzumab-treated female patients (pts) from the clinical development program.
Methods: In phase 2 (CAMMS223 [NCT00050778]) and phase 3 (CARE-MS I [NCT00530348], CARE-MS II [NCT00548405]) studies, pts received 2 annual courses of alemtuzumab. Pts could enter an extension (NCT00930553) for ≥48 mo, and then a second extension for further long-term evaluation (TOPAZ; NCT02255656), both with as-needed alemtuzumab retreatment. Pregnant/lactating pts were ineligible for treatment but remained on study for safety follow-up.
Results: As of 1 April 2017, 248 pregnancies occurred in 156 of 972 alemtuzumab-treated female pts (mean [SD] age at conception, 32.5 [4.4] years (y); mean [SD] time from last alemtuzumab dose to conception, 34.4 [22.7] mo; 9 within 4 mo of dosing), with 218 completed, 14 ongoing, and 16 with unknown outcomes. Of completed pregnancies with known outcomes, 147 (67%) were live births with no congenital abnormalities or birth defects. There were 48 (22% overall; < 35 y: 13%, ≥35 y: 33%) spontaneous abortions, 22 (10%) elective abortions, and 1 (0.5%) stillbirth (nuchal cord and amniotic band syndrome; reported previously). Elective abortions were due to personal choice (n=6), extrauterine pregnancy (n=3), anembryonic gestation (n=2), chromosomal abnormality (n=2), or foetal defect
(n=1; cystic hygroma and hypoplastic heart, reported previously); 8 had no information available.
Conclusions: In the alemtuzumab MS clinical trials, the most common outcome was delivery of full-term healthy infants. To date, there has been no signal for teratogenicity. The spontaneous abortion rate was comparable with rates seen in treatment-naive MS pts (5%-21%) and the general population (17%-22%). For MS pts outside the clinical development program, real-world data are currently collected by the International Lemtrada Pregnancy Exposure Registry, a prospective, noninterventional, observational safety study enrolling pts in ≥19 countries who become pregnant within 4 mo of alemtuzumab exposure.
Study support: Sanofi.
Disclosure:
DR: Consulting fees (Bayer Schering, Biogen, Merck Serono, Novartis, Roche, Sanofi, and Teva Neuroscience); research support (Biogen, GW Pharma, Merck Serono, Mitsubishi, Novartis, Sanofi Genzyme, and Teva Neuroscience).
JO: Consulting and/or speaking fees (Biogen-Idec, EMD Serono, Sanofi Genzyme, Novartis, Roche, and Teva); grant/research support (Biogen).
CC: Compensation for serving as editor, associate editor, or member of an editorial advisory board (Birth Defects Research Part A: Clinical and Molecular Teratology); grant/research support (AAAAI/VAMPS, AbbVie Laboratories, Apotex, Barr Laboratories, Bristol Myers/Squibb, California Department of Public Health, CDC, Celgene, Hoffmann-La Roche, Genentech, HRSA, IHC, Janssen Biotech, NIAAA, NIH/HIGM, Pfizer, Sanofi Genzyme, State of California, and UCB Pharma.
KH: Speaker honoraria and research support (Almirall, Bayer, Biogen, Merck, Novartis, Sanofi Genzyme, and Teva).
PM: Consulting and speaker fees (Biogen, Novartis, Sanofi Genzyme, and Teva).
SO: Speaker fees (Serono Symposia International Foundation).
DHM and ND: Employees of Sanofi.
DASC: Consulting fees and grant/research support (Sanofi Genzyme); lecture fees (Bayer-Schering Pharma and Sanofi Genzyme).
Abstract: P749
Type: Poster
Abstract Category: Therapy - disease modifying - 29 Risk management for disease modifying treatments
Background: Alemtuzumab is approved in >60 countries for the treatment of RRMS. Although alemtuzumab is low/undetectable in serum within 30 days of IV administration, women of childbearing potential are advised to use effective contraception for 4 months (mo) after treatment. Murine studies show no alemtuzumab-related teratogenicity, but no controlled human clinical studies of alemtuzumab in pregnancy exist.
Goal: Provide updated pregnancy outcomes in alemtuzumab-treated female patients (pts) from the clinical development program.
Methods: In phase 2 (CAMMS223 [NCT00050778]) and phase 3 (CARE-MS I [NCT00530348], CARE-MS II [NCT00548405]) studies, pts received 2 annual courses of alemtuzumab. Pts could enter an extension (NCT00930553) for ≥48 mo, and then a second extension for further long-term evaluation (TOPAZ; NCT02255656), both with as-needed alemtuzumab retreatment. Pregnant/lactating pts were ineligible for treatment but remained on study for safety follow-up.
Results: As of 1 April 2017, 248 pregnancies occurred in 156 of 972 alemtuzumab-treated female pts (mean [SD] age at conception, 32.5 [4.4] years (y); mean [SD] time from last alemtuzumab dose to conception, 34.4 [22.7] mo; 9 within 4 mo of dosing), with 218 completed, 14 ongoing, and 16 with unknown outcomes. Of completed pregnancies with known outcomes, 147 (67%) were live births with no congenital abnormalities or birth defects. There were 48 (22% overall; < 35 y: 13%, ≥35 y: 33%) spontaneous abortions, 22 (10%) elective abortions, and 1 (0.5%) stillbirth (nuchal cord and amniotic band syndrome; reported previously). Elective abortions were due to personal choice (n=6), extrauterine pregnancy (n=3), anembryonic gestation (n=2), chromosomal abnormality (n=2), or foetal defect
(n=1; cystic hygroma and hypoplastic heart, reported previously); 8 had no information available.
Conclusions: In the alemtuzumab MS clinical trials, the most common outcome was delivery of full-term healthy infants. To date, there has been no signal for teratogenicity. The spontaneous abortion rate was comparable with rates seen in treatment-naive MS pts (5%-21%) and the general population (17%-22%). For MS pts outside the clinical development program, real-world data are currently collected by the International Lemtrada Pregnancy Exposure Registry, a prospective, noninterventional, observational safety study enrolling pts in ≥19 countries who become pregnant within 4 mo of alemtuzumab exposure.
Study support: Sanofi.
Disclosure:
DR: Consulting fees (Bayer Schering, Biogen, Merck Serono, Novartis, Roche, Sanofi, and Teva Neuroscience); research support (Biogen, GW Pharma, Merck Serono, Mitsubishi, Novartis, Sanofi Genzyme, and Teva Neuroscience).
JO: Consulting and/or speaking fees (Biogen-Idec, EMD Serono, Sanofi Genzyme, Novartis, Roche, and Teva); grant/research support (Biogen).
CC: Compensation for serving as editor, associate editor, or member of an editorial advisory board (Birth Defects Research Part A: Clinical and Molecular Teratology); grant/research support (AAAAI/VAMPS, AbbVie Laboratories, Apotex, Barr Laboratories, Bristol Myers/Squibb, California Department of Public Health, CDC, Celgene, Hoffmann-La Roche, Genentech, HRSA, IHC, Janssen Biotech, NIAAA, NIH/HIGM, Pfizer, Sanofi Genzyme, State of California, and UCB Pharma.
KH: Speaker honoraria and research support (Almirall, Bayer, Biogen, Merck, Novartis, Sanofi Genzyme, and Teva).
PM: Consulting and speaker fees (Biogen, Novartis, Sanofi Genzyme, and Teva).
SO: Speaker fees (Serono Symposia International Foundation).
DHM and ND: Employees of Sanofi.
DASC: Consulting fees and grant/research support (Sanofi Genzyme); lecture fees (Bayer-Schering Pharma and Sanofi Genzyme).