Study: Be Cautious When Using Anti-TNFs in Pregnancy

Pregnant women taking tumor necrosis factor inhibitors at conception experienced a higher rate of spontaneous abortion than did patients who did not.

The data, culled from the British Society for Rheumatology Biologics Registry, are from the “largest detailed prospective collection of pregnancy outcomes in women with arthritis-related diseases exposed to anti-TNF therapy” to date, according to the authors. However, the study was unable to control for the possibility that disease severity itself plays a role in adverse pregnancy outcomes.

Nevertheless, “no firm conclusions can be drawn about the safety of anti-TNF therapy during pregnancy and, without further evidence, guidelines which suggest these drugs should be avoided at the time of conception must remain,” recommended Dr. Suzanne M.M. Verstappen of the University of Manchester's Arthritis Research UK Epidemiology Unit, and her colleagues. They looked at women who received adalimumab, etanercept, or infliximab either at conception or at any time prior to conception. A subset was also exposed to methotrexate and/or leflunomide at time of conception in addition to the anti-TNFs. A fourth cohort with active rheumatoid arthritis had no history of anti-TNF use, but rather received nonbiological disease-modifying antirheumatic drugs (DMARDs), excluding methotrexate and leflunomide (Ann. Rheum. Dis. 2011 [doi:10.1136/ard.2010.140822

Among cohort Ia, which included 20 women (21 pregnancies) who took anti-TNFs plus either methotrexate and/or leflunomide at conception, there were 10 live births, 4 terminations, and 7 (33%) spontaneous abortions (miscarriages occurring prior to 20 weeks or to viability outside the womb). Among cohort Ib, which included 44 women who took anti-TNFs at conception, but not methotrexate or leflunomide, there were 50 pregnancies. They included 32 live births among this cohort, 4 terminations, 12 spontaneous abortions (24%) and 2 intrauterine deaths (occurring post 20 weeks). There was also one neonatal death registered. The women who had taken anti-TNFs in the past, but not at the time of conception (cohort II), did have seemingly better outcomes: the 59 pregnancies (54 women) resulted in live births in 46 cases (including one of two twins), terminations in 2, and spontaneous abortions in 10 (17%). There were two intrauterine deaths, including the twin death. Among the 10 pregnancies in 10 women who had no history of anti-TNF use (cohort III), there were zero terminations and one spontaneous abortion (10%).

The British Society for Rheumatology receives restricted income from Abbott Laboratories, Biovitrum, Shering-Plough, Wyeth Pharmaceuticals, and Roche. The authors added that they had no personal competing interests in relation to this study. The society also receives funding from several pharmaceutical companies, including the makers of anti-TNFs.

Pregnant women taking tumor necrosis factor inhibitors at conception experienced a higher rate of spontaneous abortion than did patients who did not.

The data, culled from the British Society for Rheumatology Biologics Registry, are from the “largest detailed prospective collection of pregnancy outcomes in women with arthritis-related diseases exposed to anti-TNF therapy” to date, according to the authors. However, the study was unable to control for the possibility that disease severity itself plays a role in adverse pregnancy outcomes.

Nevertheless, “no firm conclusions can be drawn about the safety of anti-TNF therapy during pregnancy and, without further evidence, guidelines which suggest these drugs should be avoided at the time of conception must remain,” recommended Dr. Suzanne M.M. Verstappen of the University of Manchester's Arthritis Research UK Epidemiology Unit, and her colleagues. They looked at women who received adalimumab, etanercept, or infliximab either at conception or at any time prior to conception. A subset was also exposed to methotrexate and/or leflunomide at time of conception in addition to the anti-TNFs. A fourth cohort with active rheumatoid arthritis had no history of anti-TNF use, but rather received nonbiological disease-modifying antirheumatic drugs (DMARDs), excluding methotrexate and leflunomide (Ann. Rheum. Dis. 2011 [doi:10.1136/ard.2010.140822

Among cohort Ia, which included 20 women (21 pregnancies) who took anti-TNFs plus either methotrexate and/or leflunomide at conception, there were 10 live births, 4 terminations, and 7 (33%) spontaneous abortions (miscarriages occurring prior to 20 weeks or to viability outside the womb). Among cohort Ib, which included 44 women who took anti-TNFs at conception, but not methotrexate or leflunomide, there were 50 pregnancies. They included 32 live births among this cohort, 4 terminations, 12 spontaneous abortions (24%) and 2 intrauterine deaths (occurring post 20 weeks). There was also one neonatal death registered. The women who had taken anti-TNFs in the past, but not at the time of conception (cohort II), did have seemingly better outcomes: the 59 pregnancies (54 women) resulted in live births in 46 cases (including one of two twins), terminations in 2, and spontaneous abortions in 10 (17%). There were two intrauterine deaths, including the twin death. Among the 10 pregnancies in 10 women who had no history of anti-TNF use (cohort III), there were zero terminations and one spontaneous abortion (10%).

The British Society for Rheumatology receives restricted income from Abbott Laboratories, Biovitrum, Shering-Plough, Wyeth Pharmaceuticals, and Roche. The authors added that they had no personal competing interests in relation to this study. The society also receives funding from several pharmaceutical companies, including the makers of anti-TNFs.

Pregnant women taking tumor necrosis factor inhibitors at conception experienced a higher rate of spontaneous abortion than did patients who did not.

The data, culled from the British Society for Rheumatology Biologics Registry, are from the “largest detailed prospective collection of pregnancy outcomes in women with arthritis-related diseases exposed to anti-TNF therapy” to date, according to the authors. However, the study was unable to control for the possibility that disease severity itself plays a role in adverse pregnancy outcomes.

Nevertheless, “no firm conclusions can be drawn about the safety of anti-TNF therapy during pregnancy and, without further evidence, guidelines which suggest these drugs should be avoided at the time of conception must remain,” recommended Dr. Suzanne M.M. Verstappen of the University of Manchester's Arthritis Research UK Epidemiology Unit, and her colleagues. They looked at women who received adalimumab, etanercept, or infliximab either at conception or at any time prior to conception. A subset was also exposed to methotrexate and/or leflunomide at time of conception in addition to the anti-TNFs. A fourth cohort with active rheumatoid arthritis had no history of anti-TNF use, but rather received nonbiological disease-modifying antirheumatic drugs (DMARDs), excluding methotrexate and leflunomide (Ann. Rheum. Dis. 2011 [doi:10.1136/ard.2010.140822

Among cohort Ia, which included 20 women (21 pregnancies) who took anti-TNFs plus either methotrexate and/or leflunomide at conception, there were 10 live births, 4 terminations, and 7 (33%) spontaneous abortions (miscarriages occurring prior to 20 weeks or to viability outside the womb). Among cohort Ib, which included 44 women who took anti-TNFs at conception, but not methotrexate or leflunomide, there were 50 pregnancies. They included 32 live births among this cohort, 4 terminations, 12 spontaneous abortions (24%) and 2 intrauterine deaths (occurring post 20 weeks). There was also one neonatal death registered. The women who had taken anti-TNFs in the past, but not at the time of conception (cohort II), did have seemingly better outcomes: the 59 pregnancies (54 women) resulted in live births in 46 cases (including one of two twins), terminations in 2, and spontaneous abortions in 10 (17%). There were two intrauterine deaths, including the twin death. Among the 10 pregnancies in 10 women who had no history of anti-TNF use (cohort III), there were zero terminations and one spontaneous abortion (10%).

The British Society for Rheumatology receives restricted income from Abbott Laboratories, Biovitrum, Shering-Plough, Wyeth Pharmaceuticals, and Roche. The authors added that they had no personal competing interests in relation to this study. The society also receives funding from several pharmaceutical companies, including the makers of anti-TNFs.