PREGNANCY OUTCOMES AFTER EXPOSURE TO TNF-? INHIBITORS FOR THE TREATMENT OF ARTHRITIC DISEASES: A META-ANALYSIS OF OBSERVATIONAL STUDIES TNF-? Inhibitors and Pregnancy Outcomes in Arthritic Diseases
Main Article Content
Keywords
PREGNANCY, TNF-? INHIBITORS, Autoimmune arthritic diseases, drug safety
Abstract
Background
Autoimmune arthritic diseases affect many women of child-bearing age. Tumour necrosis factor (TNF)-? inhibitors are currently used for the treatment of various immune-mediated diseases during pregnancy. However, there has been no evaluation of safety in the treatment of arthritic diseases during gestation.
Objective
To analyze the risk of adverse pregnancy and neonatal outcomes after treatment of arthritic diseases with TNF-? inhibitors.
Methods
Major databases including Ovid MEDLINE, Embase, and Web of Science, were searched inclusive to April 2016. Observational prospective cohort studies evaluating pregnancy outcomes (birth defects, Spontaneous abortion, therapeutic abortion, birth weight, preterm birth, live birth) after exposure to TNF-? inhibitors for the treatment of arthritic diseases during pregnancy were included. Data on pregnancy and neonatal outcomes was extracted from all included studies. A meta-analysis was performed using inverse-variance random effect with a 95% confidence interval (95%CI) and p<0.05.
Results
Eight prospective studies with comparison groups were included in the meta-analysis. TNF-? inhibitors were associated with significantly higher risks of low birth weight (odds ratio (OR), 1.43; 95%CI, 1.00–2.04) and significantly lower rates of live birth (OR, 0.61; 95%CI, 0.38–0.98). However, birth defects, therapeutic abortion, spontaneous abortion, and preterm birth were not significantly different between the 2 groups.
Conclusion
Treatment of arthritic diseases with TNF-? inhibitors during pregnancy increases the risk of lower birth weight and decreases the rate of live birth in this population. While duration of treatment and gestational age at exposure may play a role in these outcomes, evaluation of risk versus benefit is crucial in this patient population.
Autoimmune arthritic diseases affect many women of child-bearing age. Tumour necrosis factor (TNF)-? inhibitors are currently used for the treatment of various immune-mediated diseases during pregnancy. However, there has been no evaluation of safety in the treatment of arthritic diseases during gestation.
Objective
To analyze the risk of adverse pregnancy and neonatal outcomes after treatment of arthritic diseases with TNF-? inhibitors.
Methods
Major databases including Ovid MEDLINE, Embase, and Web of Science, were searched inclusive to April 2016. Observational prospective cohort studies evaluating pregnancy outcomes (birth defects, Spontaneous abortion, therapeutic abortion, birth weight, preterm birth, live birth) after exposure to TNF-? inhibitors for the treatment of arthritic diseases during pregnancy were included. Data on pregnancy and neonatal outcomes was extracted from all included studies. A meta-analysis was performed using inverse-variance random effect with a 95% confidence interval (95%CI) and p<0.05.
Results
Eight prospective studies with comparison groups were included in the meta-analysis. TNF-? inhibitors were associated with significantly higher risks of low birth weight (odds ratio (OR), 1.43; 95%CI, 1.00–2.04) and significantly lower rates of live birth (OR, 0.61; 95%CI, 0.38–0.98). However, birth defects, therapeutic abortion, spontaneous abortion, and preterm birth were not significantly different between the 2 groups.
Conclusion
Treatment of arthritic diseases with TNF-? inhibitors during pregnancy increases the risk of lower birth weight and decreases the rate of live birth in this population. While duration of treatment and gestational age at exposure may play a role in these outcomes, evaluation of risk versus benefit is crucial in this patient population.
References
1. Mo F, Morrison H, Neutel IC. Population attributable risk from obesity to arthritis in the Canadian population health longitudinal survey 1994-2006. Int J Rheum Dis 2014;17(6):628–34.
2. Turcotte M. Women and health,women in Canada: A gender-based statistical report, 2011. http://www.statcan. gc.ca/pub/89-503-x/2010001/article/11543-eng.pdf. Accessed Feb/12, 2018.
3. Cressman AM, Petrovic V, Piquette-Miller M. Inflammation-mediated changes in drug transporter expression/ activity: Implications for therapeutic drug response. Expert Rev Clin Pharmacol 2012;5(1):69–89.
4. Jarosova K., Hejduk K., Uher M., Vencovsky J. Pregnancy outcome in adult juvenile idiopathic arthritis patients treated with biologic agents. Updated 201473.
5. Accortt N, Carman WJ, Enger C, et al. Birth outcomes among infants of women with chronic inflammatory arthritis or psoriasis treated and not treated with etaner-cept (ENBREL) during pregnancy. Updated 201574.
6. Mouyis M, Thornton C, Williams D, Giles I. Pregnancy in psoriatic arthritis: A case series. Updated 201567.
7. Reed SD, Vollan TA, Svec MA. Pregnancy outcomes in women with rheumatoid arthritis in washington state. Matern Child Health J 2006;10(4):361–66.
8. Barnabe C, Faris PD, Quan H. Canadian pregnancy outcomes in rheumatoid arthritis and systemic lupus erythematosus. Int J Rheumatol 2011;2011:345727.
9. Chen JS, Ford JB, Roberts CL, Simpson JM, March LM. Pregnancy outcomes in women with juvenile idiopathic arthritis: A population-based study. Rheumatology (Oxford). 2013;52(6):1119–25.
10. Chambers CD, Johnson DL. Emerging data on the use of anti-tumor necrosis factor-alpha medications in pregnancy. Birth Defects Res A Clin Mol Teratol 2012;94(8):607–11.
11. Julsgaard M, Christensen LA, Gibson PR, et al. Concentrations of adalimumab and infliximab in mothers and newborns, and effects on infection. Gastroenterol-ogy 2016.
12. Clowse ME. The use of anti-TNFalpha medications for rheumatologic disease in pregnancy. Int J Womens Health 2010;2:199–209.
13. Carter JD, Ladhani A, Ricca LR, Valeriano J, Vasey FB. A safety assessment of tumor necrosis factor antagonists during pregnancy: A review of the food and drug administration database. J Rheumatol 2009;36(3):635–41.
14. Bazzani C, Scrivo R, Andreoli L, et al. Prospectively-followed pregnancies in patients with inflammatory arthritis taking biological drugs: An Italian multicentre study. Updated 2015.
15. Chambers CD, Johnson DL, Luo Y, et al. Pregnancy outcome in women treated with adalimumab for rheumatoid arthritis: An update on the OTIS autoimmune diseases in pregnancy project. Pharmacoepidemiol Drug Saf 2015.;24:399.
16. Strangfeld A., Pattloch D, Spilka M, et al. Pregnancies in patients with rheumatoid arthritis: Treatment decisions, course of the disease, and pregnancy outcomes. Updated 201574.
17. Broms G, Granath F, Ekbom A, et al. Low risk of birth defects for infants whose mothers are treated with anti-tumor necrosis factor agents during pregnancy. Clin Gastroenterol Hepatol 2016;14(2):234–41. e1–5.
18. Ince-Askan H, Dolhain RJ. Pregnancy and rheumatoid arthritis. Best Pract Res Clin Rheumatol 2015;29(4–5):580–96.
19. Mahadevan U, Wolf D, Stach C, et al. Outcomes of pregnancy in subjects exposed to certolizumab pegol. Updated 2012107.
20. Stewart LA, Clarke M, Rovers M, et al. Preferred reporting items for systematic review and meta-analyses of individual participant data: The PRISMA-IPD statement. JAMA 2015;313(16):1657–65.
21. Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ 2003;327(7414):557–560.
22. Guyatt G, Oxman AD, Akl EA, et al. GRADE guidelines: 1. introduction-GRADE evidence profiles and summary of findings tables. J Clin Epidemiol 2011;64(4):383–94.
23. Giacuzzo S, Padovan M, Capucci R, et al. Pregnancy outcome of mothers with rheumatic diseases exposed to biological agent during pregnancy: A single-centre study. Updated 201473.
24. Verstappen SM, King Y, Watson KD, Symmons DP, Hyrich KL, BSRBR Control Centre Consortium, BSR Biologics Register. Anti-TNF therapies and pregnancy: Outcome of 130 pregnancies in the british society for rheumatology biologics register. Ann Rheum Dis 2011;70(5):823–26.
25. Chakravarty E, Langen E, Druzin M, Liaqat M. High rate of preterm birth in pregnancies complicated by rheumatoid arthritis. Updated 2011.
26. Wells G, Shea B, O’Connell D, et al. The Newcastle-Ottawa scale (NOS) for assessing the quality of nonrandomized studies in meta-analyses. Available at: http:// www.ohri.ca/programs/clinical_epidemiology/oxford. asp. Updated 2014.
27. Weber-Schoendorfer C, Oppermann M, Wacker E, et al. Pregnancy outcome after TNF-alpha inhibitor therapy during the first trimester: A prospective multicentre cohort study. Br J Clin Pharmacol 2015;80(4):727–39.
28. Katz J, Keenan G, Snith D, Lichtenstein G. Outcome of pregnancy in patients receiving infliximab for the treatment of crohn’s disease and rheumatoid arthritis. Gastroenterology 2003;124(4):A7–A7.
29. Clowse MEB., Wolf DC, Golembesky A, et al. Characteristics and outcomes of prospectively-reported pregnancies exposed to certolizumab pegol from a safety database. Updated 201567.
30. Komaki F, Komaki Y, Micic D, et al. Outcome of pregnancy and neonatal complications with anti-tumor necrosis factor-alpha use in females with immune mediated diseases; a systematic review and meta-analysis. J Autoimmun 2016.
31. Ginsberg Y, Khatib N, Weiner Z, Beloosesky R. Maternal inflammation, fetal brain implications and suggested neuroprotection: A summary of 10 years of research in animal models. Rambam Maimonides Med J 2017;8(2):10.5041/RMMJ.10305.
32. Guiddir T, Fremond M, Triki TB, et al. Anti-TNF-alpha therapy may cause neonatal neutropenia. Pediatrics. 2014;134(4): E1189–E1193.
33. Niebyl JR, Simpson JL. Teratology and drugs in pregnancy. Global Libr Women’s Med 2009.
34. Panchal S, Flint J, Venne VD, et al. A systematic analysis of the safety of prescribing anti-rheumatic immunosuppressive and biologic drugs in pregnant women with inflammatory arthritis. Updated 201473.
35. Mahadevan U, Kane S, Sandborn W, et al. Intentional infliximab use during pregnancy for induction or maintenance of remission in crohn’s disease. Aliment Pharmacol Ther 2005;21(6):733–38.
36. Mahadevan U, Wolf DC, Dubinsky M, et al. Placental transfer of anti-tumor necrosis factor agents in pregnant patients with inflammatory bowel disease. Clin Gastroenterol Hepatol 2013;11(3):286–92; quiz e24.
37. Hoxha A, Calligaro A, Favaro M, et al. Pregnancy and anti-TNFalpha drugs: Experience of four centres. Updated 201574.
38. Johnson DL, Jones KL, Chambers CD, Salas E. 142 pregnancy outcomes in women exposed to adalimumab: The OTIS autoimmune diseases in pregnancy project. Gastroenterology 2009;136(5):A-27.
39. Chakravarty EF, Sanchez-Yamamoto D, Bush TM. The use of disease modifying antirheumatic drugs in women with rheumatoid arthritis of childbearing age: A survey of practice patterns and pregnancy outcomes. J Rheumatol 2003;30(2):241–46.
2. Turcotte M. Women and health,women in Canada: A gender-based statistical report, 2011. http://www.statcan. gc.ca/pub/89-503-x/2010001/article/11543-eng.pdf. Accessed Feb/12, 2018.
3. Cressman AM, Petrovic V, Piquette-Miller M. Inflammation-mediated changes in drug transporter expression/ activity: Implications for therapeutic drug response. Expert Rev Clin Pharmacol 2012;5(1):69–89.
4. Jarosova K., Hejduk K., Uher M., Vencovsky J. Pregnancy outcome in adult juvenile idiopathic arthritis patients treated with biologic agents. Updated 201473.
5. Accortt N, Carman WJ, Enger C, et al. Birth outcomes among infants of women with chronic inflammatory arthritis or psoriasis treated and not treated with etaner-cept (ENBREL) during pregnancy. Updated 201574.
6. Mouyis M, Thornton C, Williams D, Giles I. Pregnancy in psoriatic arthritis: A case series. Updated 201567.
7. Reed SD, Vollan TA, Svec MA. Pregnancy outcomes in women with rheumatoid arthritis in washington state. Matern Child Health J 2006;10(4):361–66.
8. Barnabe C, Faris PD, Quan H. Canadian pregnancy outcomes in rheumatoid arthritis and systemic lupus erythematosus. Int J Rheumatol 2011;2011:345727.
9. Chen JS, Ford JB, Roberts CL, Simpson JM, March LM. Pregnancy outcomes in women with juvenile idiopathic arthritis: A population-based study. Rheumatology (Oxford). 2013;52(6):1119–25.
10. Chambers CD, Johnson DL. Emerging data on the use of anti-tumor necrosis factor-alpha medications in pregnancy. Birth Defects Res A Clin Mol Teratol 2012;94(8):607–11.
11. Julsgaard M, Christensen LA, Gibson PR, et al. Concentrations of adalimumab and infliximab in mothers and newborns, and effects on infection. Gastroenterol-ogy 2016.
12. Clowse ME. The use of anti-TNFalpha medications for rheumatologic disease in pregnancy. Int J Womens Health 2010;2:199–209.
13. Carter JD, Ladhani A, Ricca LR, Valeriano J, Vasey FB. A safety assessment of tumor necrosis factor antagonists during pregnancy: A review of the food and drug administration database. J Rheumatol 2009;36(3):635–41.
14. Bazzani C, Scrivo R, Andreoli L, et al. Prospectively-followed pregnancies in patients with inflammatory arthritis taking biological drugs: An Italian multicentre study. Updated 2015.
15. Chambers CD, Johnson DL, Luo Y, et al. Pregnancy outcome in women treated with adalimumab for rheumatoid arthritis: An update on the OTIS autoimmune diseases in pregnancy project. Pharmacoepidemiol Drug Saf 2015.;24:399.
16. Strangfeld A., Pattloch D, Spilka M, et al. Pregnancies in patients with rheumatoid arthritis: Treatment decisions, course of the disease, and pregnancy outcomes. Updated 201574.
17. Broms G, Granath F, Ekbom A, et al. Low risk of birth defects for infants whose mothers are treated with anti-tumor necrosis factor agents during pregnancy. Clin Gastroenterol Hepatol 2016;14(2):234–41. e1–5.
18. Ince-Askan H, Dolhain RJ. Pregnancy and rheumatoid arthritis. Best Pract Res Clin Rheumatol 2015;29(4–5):580–96.
19. Mahadevan U, Wolf D, Stach C, et al. Outcomes of pregnancy in subjects exposed to certolizumab pegol. Updated 2012107.
20. Stewart LA, Clarke M, Rovers M, et al. Preferred reporting items for systematic review and meta-analyses of individual participant data: The PRISMA-IPD statement. JAMA 2015;313(16):1657–65.
21. Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ 2003;327(7414):557–560.
22. Guyatt G, Oxman AD, Akl EA, et al. GRADE guidelines: 1. introduction-GRADE evidence profiles and summary of findings tables. J Clin Epidemiol 2011;64(4):383–94.
23. Giacuzzo S, Padovan M, Capucci R, et al. Pregnancy outcome of mothers with rheumatic diseases exposed to biological agent during pregnancy: A single-centre study. Updated 201473.
24. Verstappen SM, King Y, Watson KD, Symmons DP, Hyrich KL, BSRBR Control Centre Consortium, BSR Biologics Register. Anti-TNF therapies and pregnancy: Outcome of 130 pregnancies in the british society for rheumatology biologics register. Ann Rheum Dis 2011;70(5):823–26.
25. Chakravarty E, Langen E, Druzin M, Liaqat M. High rate of preterm birth in pregnancies complicated by rheumatoid arthritis. Updated 2011.
26. Wells G, Shea B, O’Connell D, et al. The Newcastle-Ottawa scale (NOS) for assessing the quality of nonrandomized studies in meta-analyses. Available at: http:// www.ohri.ca/programs/clinical_epidemiology/oxford. asp. Updated 2014.
27. Weber-Schoendorfer C, Oppermann M, Wacker E, et al. Pregnancy outcome after TNF-alpha inhibitor therapy during the first trimester: A prospective multicentre cohort study. Br J Clin Pharmacol 2015;80(4):727–39.
28. Katz J, Keenan G, Snith D, Lichtenstein G. Outcome of pregnancy in patients receiving infliximab for the treatment of crohn’s disease and rheumatoid arthritis. Gastroenterology 2003;124(4):A7–A7.
29. Clowse MEB., Wolf DC, Golembesky A, et al. Characteristics and outcomes of prospectively-reported pregnancies exposed to certolizumab pegol from a safety database. Updated 201567.
30. Komaki F, Komaki Y, Micic D, et al. Outcome of pregnancy and neonatal complications with anti-tumor necrosis factor-alpha use in females with immune mediated diseases; a systematic review and meta-analysis. J Autoimmun 2016.
31. Ginsberg Y, Khatib N, Weiner Z, Beloosesky R. Maternal inflammation, fetal brain implications and suggested neuroprotection: A summary of 10 years of research in animal models. Rambam Maimonides Med J 2017;8(2):10.5041/RMMJ.10305.
32. Guiddir T, Fremond M, Triki TB, et al. Anti-TNF-alpha therapy may cause neonatal neutropenia. Pediatrics. 2014;134(4): E1189–E1193.
33. Niebyl JR, Simpson JL. Teratology and drugs in pregnancy. Global Libr Women’s Med 2009.
34. Panchal S, Flint J, Venne VD, et al. A systematic analysis of the safety of prescribing anti-rheumatic immunosuppressive and biologic drugs in pregnant women with inflammatory arthritis. Updated 201473.
35. Mahadevan U, Kane S, Sandborn W, et al. Intentional infliximab use during pregnancy for induction or maintenance of remission in crohn’s disease. Aliment Pharmacol Ther 2005;21(6):733–38.
36. Mahadevan U, Wolf DC, Dubinsky M, et al. Placental transfer of anti-tumor necrosis factor agents in pregnant patients with inflammatory bowel disease. Clin Gastroenterol Hepatol 2013;11(3):286–92; quiz e24.
37. Hoxha A, Calligaro A, Favaro M, et al. Pregnancy and anti-TNFalpha drugs: Experience of four centres. Updated 201574.
38. Johnson DL, Jones KL, Chambers CD, Salas E. 142 pregnancy outcomes in women exposed to adalimumab: The OTIS autoimmune diseases in pregnancy project. Gastroenterology 2009;136(5):A-27.
39. Chakravarty EF, Sanchez-Yamamoto D, Bush TM. The use of disease modifying antirheumatic drugs in women with rheumatoid arthritis of childbearing age: A survey of practice patterns and pregnancy outcomes. J Rheumatol 2003;30(2):241–46.
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Published
Apr 10, 2018
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How to Cite
Mirdamadi, K., Salinas, T., Vali, R., Papadimitropoulos, M., & Piquette-Miller, M. (2018). PREGNANCY OUTCOMES AFTER EXPOSURE TO TNF-? INHIBITORS FOR THE TREATMENT OF ARTHRITIC DISEASES: A META-ANALYSIS OF OBSERVATIONAL STUDIES: TNF-? Inhibitors and Pregnancy Outcomes in Arthritic Diseases. Journal of Population Therapeutics and Clinical Pharmacology, 25(1), e53-e56. https://doi.org/10.22374/1710-6222.25.1.5
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