B-cell Depletion in Offspring to Women With MS Under Immunomodulatory Treatment
NCT ID: NCT06711354
Last Updated: 2024-12-02
Study Results
Results pending
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
Recruitment Status
NOT_YET_RECRUITING
Total Enrollment
111 participants
Study Classification
OBSERVATIONAL
Study Start Date
2025-06-30
Study Completion Date
2025-12-31
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
The overall aim of the study is to gain knowledge about consequences for the child´s humoral immunosystem in mothers with multiple sclerosis and due to their immunomodulating treatments. Of special interest is when the mother is treated with monoclonal CD20-antibody like rituximab, ocrelizumab and ofatumumab shortly before (within six months prior to conception) and during pregnancy. Specific aims of the study are to:
* Investigate if the humoral immunosystem is fully functioning at birth in children born to mothers with MS
* Investigate if the humoral immunosystem at birth in children born to mothers with MS is influenced by the mothers immunomodulating treatment
* Investigate if monoclonal CD20-antibodies are fully eliminated in women treated with monoclonal CD20-antibodies within 12 months prior to conception.
* Determine if children who have been exposed to monoclonal CD20-antibody in utero have reduced markers of successful B-cell production at birth.
* Investigate the response to the Rota virus vaccine, a life-vaccine that is offered 6 weeks after birth to all children born after September 2019, in children to women treated with rituximab before or during pregnancy.
* Investigate the response to other vaccines (DTP, Polio, HiB, pneumococcus given at 3 and 5 months after birth) the earliest one months after vaccination.
* Investigate the occurrence of infections in the first-year post-partum for the mother and child due to hypogammaglobulinemia, b-cell depletion, and exposure to monoclonal CD20-antibody.
* Investigate if oral exposure to rituximab through mother´s breastmilk is resulting in B-cell reduction in the child.
* Investigate if the humoral immunosystem is fully functioning at birth in children born to mothers with MS
* Investigate if the humoral immunosystem at birth in children born to mothers with MS is influenced by the mothers immunomodulating treatment
* Investigate if monoclonal CD20-antibodies are fully eliminated in women treated with monoclonal CD20-antibodies within 12 months prior to conception.
* Determine if children who have been exposed to monoclonal CD20-antibody in utero have reduced markers of successful B-cell production at birth.
* Investigate the response to the Rota virus vaccine, a life-vaccine that is offered 6 weeks after birth to all children born after September 2019, in children to women treated with rituximab before or during pregnancy.
* Investigate the response to other vaccines (DTP, Polio, HiB, pneumococcus given at 3 and 5 months after birth) the earliest one months after vaccination.
* Investigate the occurrence of infections in the first-year post-partum for the mother and child due to hypogammaglobulinemia, b-cell depletion, and exposure to monoclonal CD20-antibody.
* Investigate if oral exposure to rituximab through mother´s breastmilk is resulting in B-cell reduction in the child.
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
Multiple sclerosis (MS) is a chronic inflammatory disorder of the central nervous system affecting more women than men and typically manifests during reproductive ages (1). The disease and associated treatments therefore have a large impact on family planning. While trying to conceive most clinicians recommend discontinuation of disease-modifying drug use (DMD) before conception unless the risk of disease worsening outweighs the risk to the fetus (2,3). Patients with active disease may need to continue DMD treatment until conception or even during pregnancy. Furthermore, given that nearly half of all pregnancies are unplanned (4-6) women with MS may occasionally become pregnant during or shortly after receiving treatment. As such, gathering information on the effect of pregnancy exposure to DMD is crucial for the management of reproductive issues in women with MS.
Rituximab, a chimeric monoclonal B cell-depleting anti-CD20 antibody, is frequently used off-label for the treatment of MS in Sweden (7). The drug targets CD20 on the cell surface of B cells and effectively depletes them. Previously recommendations of rituximab was withdrawn at least one year prior to a planned pregnancy. Given the pharmacokinetics with a halftime of around 24 days current Swedish guidelines accept a minimum of 3-4 months between last infusion and conception. Rituximab is a chimeric antibody of the immunoglobulin G1 kappa type and is therefore actively transported over the blood-placenta barrier, mainly during the third trimester but starting already in the second trimester. Small case series and reports show that rituximab administered during the third trimester suppresses neonatal b-cell development (8-12). After six months, usually, b-cells levels normalize but effects may not be clinically apparent at birth but may influence response to vaccinations early in life and increase susceptibility to infections.
Severe combined immunodeficiency (SCID) is included in the Swedish national neonatal disease screening program, testing is performed at Centrum för Medfödda Metabola Sjukdomar (CMMS), in parallel with screening tests for other diseases, on blood samples in the form of dry blood spots (DBS) taken within 48 hours after birth. The SCID screening consists of assessing markers of T and B cell production, T-cell receptor excision circles (TREC) (13) and kappa-deleting recombination excision circles (KREC)(14) , respectively. Both are circular fragments of DNA that are excised during the gene rearrangements necessary for the formation of functional T- and B-cell receptors. KRECs are formed during the rearrangement of the kappa light chain gene and occurs in the bone marrow at the small pre-B-cell stage. CD20 is already expressed on the surface of these B-cell precursors and they may therefore be targeted by rituximab and other monoclonal anti-CD20 antibodies (15). Each cell forms one KREC copy, which by necessity is passed to only one of the cells after cell division. Consequently, a proportion of mature B-cells in the circulation will also carry KRECs, and because they express CD20 they may be depleted by rituximab.
We hypothesize that if rituximab inhibits B-cell formation in the fetus of a pregnant mother treated with the drug, this can be detected in the form of reduced KREC results. A case report that describes a child of a rituximab treated mother that had reduced KREC results at birth has been published suggesting that such effects occur (16). It has also been shown that broad immunosuppressants, in particular the purine analogue azathioprine, cause some KREC results that are under the cutoff in the neonatal screening in Sweden (17). More knowledge is needed regarding the safety of rituximab for the fetus during pregnancy to facilitate clinical decisions in this complex situation, being able to identify offspring with insufficient B-cell counts and consequently at higher risks for infection and influence of vaccination responds. Such knowledge will facilitate clinical decisions and may help identify offspring with insufficient B cell counts and consequently at higher risks for infection and poor vaccine response.
The experimental plan includes a retrospective part as well as a prospective part.
The retrospective part of the study will take advantage of already existing blood samples from the national newborn screening program and examine the KREC results of all children born to rituximab treated mothers with MS in Stockholm during the past 10 years. Information on DMD treatment, time of conception, B-cell level, immunoglobulin levels in the mothers at the end of each trimester are routinely collected and recorded in the Swedish Multiple Sclerosis registry (SMSreg). Mothers that have been treated with monoclonal CD-20 antibodies and other MS specific DMTs during pregnancy or within twelve months before conception and have successfully delivered a child will be included in the study. After informed consent has been received from the parents our collaborators at CMMS will extract KREC results if available from either the screening program or the preceding pilot study(17). If results are not available, the DBS samples will be retrieved and KREC analyzed specifically for this study. If the combined KREC results are ambiguous we have the option to retrieve DBS samples for all included children and perform an in-house assay developed at CMMS to confirm B-cell deficiency by determining abundance of CD19 transcripts in the sample. Furthermore, to be able to correlate B-cell deficiency to drug concentration in the child, DBS can be sent for drug level detection to our collaborators at the Haukeland University Hospital laboratory. The mothers B-cell deficiency and its consequence on immunoglobulin levels will also be assessed in the analysis.
In the prospective part of the study we plan to address if a reduction in the levels of KREC and/or CD19+ B-cells at birth of offspring to women with MS has clinical significance. Mothers with MS, regardless of treatment, that have successfully delivered or will deliver a child will be asked for informed consent included if applicable.
1. At clinical routine venous blood sampling immunoglobulin and B-cell levels are obtained. Additional samples, during clinical routine visit, in the becoming mother will allow analysis of drug concentration at the end of every trimester and 3 months post partum.
2. Within 1-12 months postpartum and after vaccination capillary blood samples from the child will be analyzed to detect antibodies induced by vaccination or infections to secure the ability to be able to develop antibodies despite being exposed to monoclonal CD20-antibodies in-utero or via breastmilk.
3. PKU-test is taken in the child within routine but additional analysis on drug levels and KREC will be analyzed as well as determining abundance of CD19 transcripts.
4. Within our routine contacts with the MS patient (mother) we will ask for infections in both, the mother and the child at 3 months and 1 year post-partum.
After informed consent has been received from the parents our collaborators at CMMS will also extract KREC results if available from the screening program. If results are not available, the DBS samples will be retrieved and KREC analyzed specifically for this study. If the combined KREC results are ambiguous we have the option to retrieve DBS samples for all included children and perform an in-house assay developed at CMMS to confirm B-cell deficiency by determining abundance of CD19 transcripts in the sample.
Primarily Rota virus vaccine will be considered because it is the earliest vaccination in the national vaccination program, offered at 6 weeks of age. Antibody levels for other vaccines or infections may be tested if deemed relevant. A detailed infectious and general medical history via the parents will be obtained at routine contacts between patient and health care and comparison of adverse outcomes between children with mothers exposed to rituximab and children to mothers with MS but without rituximab treatment within 12 months prior to conception as well as for children with and without apparent reduction in the levels of KREC and/or B-cell depletion due to in utero exposure to rituximab and children with normal KREC levels will be summarized.
In Canada, Germany and the US, breastfeeding despite receiving anti-CD20 antibody therapy is getting more common, assuming the antibody cannot be enterally absorbed hence eliminated fecally ungraded. Swedish recommendations at present are cessation of breastfeeding when starting DMT however more women choose to breastfeed regardless. We would like to offer a follow-up with breastmilk samples and blood samples in the child one month after drug application for drug level detection in breastmilk and child and B-cell level analysis in the child.
Sample analysis of B-cell levels, IgG and IgM levels as well as specific antibodies as detection for immune responds to vaccination will be analyzed with clinically established methods via the lab at Karolinska University Hospital and Lennart Svenssons lab in Linköping, Sweden. Blood sampling from the child will be performed at specialized blood sampling centers for children e.g. Karolinska university hospital. KRECs and abundance of CD19 transcripts will we analyzed in dried blood spots at CMMS with an established method within the clinics. As there is no existing established high-quality method in Sweden, we will have to send drug level analysis to the Bergen University in Norway, our collaborator. They will use ELISA and high-performance liquid chromatography-electrospray ionization mass spectrometry method to analyses drug levels in blood, breast milk and dried blood spots.
Descriptive data and differences in drug levels, cell levels, infection rate and KREC levels between women with MS who have been exposed to ant-CD20 antibodies and not close to their pregnancy and their offspring will be tested with chi2-tests or Wilcoxon rank sum test, where appropriate. IgG levels will be analyzed using a linear mixed effect model, including number of doses of administered DMT (i.e. RTX or other DMTs) as random effect, while age, sex, previous DMT, administered DMT and the interaction of doses and administered DMT as fixed effects. P-values \<0.05 will be considered statistically significant. Non-parametric variables will be presented as median (range), and normally distributed variables as mean (SD).
The dilemma of balancing the mothers need for effective treatment against potential harmful effects to the fetus is a common clinical problem. It is virtually impossible to study the effects of drugs on the developing child apart from gathering observational data from individual cases where, for any reason, the mother did receive a certain drug. In Sweden the conditions are especially good to gather information on the effects of in utero exposure to B-cell depleting drugs because the unique propensity to treat MS-patients with monoclonal CD20-antibodies (e.g. rituximab) in combination with a newborn screening program that includes a marker for B-cell deficiency. The study results will have direct impact on the clinical management of MS-patients with aggressive disease and family planning wishes.
Rituximab, a chimeric monoclonal B cell-depleting anti-CD20 antibody, is frequently used off-label for the treatment of MS in Sweden (7). The drug targets CD20 on the cell surface of B cells and effectively depletes them. Previously recommendations of rituximab was withdrawn at least one year prior to a planned pregnancy. Given the pharmacokinetics with a halftime of around 24 days current Swedish guidelines accept a minimum of 3-4 months between last infusion and conception. Rituximab is a chimeric antibody of the immunoglobulin G1 kappa type and is therefore actively transported over the blood-placenta barrier, mainly during the third trimester but starting already in the second trimester. Small case series and reports show that rituximab administered during the third trimester suppresses neonatal b-cell development (8-12). After six months, usually, b-cells levels normalize but effects may not be clinically apparent at birth but may influence response to vaccinations early in life and increase susceptibility to infections.
Severe combined immunodeficiency (SCID) is included in the Swedish national neonatal disease screening program, testing is performed at Centrum för Medfödda Metabola Sjukdomar (CMMS), in parallel with screening tests for other diseases, on blood samples in the form of dry blood spots (DBS) taken within 48 hours after birth. The SCID screening consists of assessing markers of T and B cell production, T-cell receptor excision circles (TREC) (13) and kappa-deleting recombination excision circles (KREC)(14) , respectively. Both are circular fragments of DNA that are excised during the gene rearrangements necessary for the formation of functional T- and B-cell receptors. KRECs are formed during the rearrangement of the kappa light chain gene and occurs in the bone marrow at the small pre-B-cell stage. CD20 is already expressed on the surface of these B-cell precursors and they may therefore be targeted by rituximab and other monoclonal anti-CD20 antibodies (15). Each cell forms one KREC copy, which by necessity is passed to only one of the cells after cell division. Consequently, a proportion of mature B-cells in the circulation will also carry KRECs, and because they express CD20 they may be depleted by rituximab.
We hypothesize that if rituximab inhibits B-cell formation in the fetus of a pregnant mother treated with the drug, this can be detected in the form of reduced KREC results. A case report that describes a child of a rituximab treated mother that had reduced KREC results at birth has been published suggesting that such effects occur (16). It has also been shown that broad immunosuppressants, in particular the purine analogue azathioprine, cause some KREC results that are under the cutoff in the neonatal screening in Sweden (17). More knowledge is needed regarding the safety of rituximab for the fetus during pregnancy to facilitate clinical decisions in this complex situation, being able to identify offspring with insufficient B-cell counts and consequently at higher risks for infection and influence of vaccination responds. Such knowledge will facilitate clinical decisions and may help identify offspring with insufficient B cell counts and consequently at higher risks for infection and poor vaccine response.
The experimental plan includes a retrospective part as well as a prospective part.
The retrospective part of the study will take advantage of already existing blood samples from the national newborn screening program and examine the KREC results of all children born to rituximab treated mothers with MS in Stockholm during the past 10 years. Information on DMD treatment, time of conception, B-cell level, immunoglobulin levels in the mothers at the end of each trimester are routinely collected and recorded in the Swedish Multiple Sclerosis registry (SMSreg). Mothers that have been treated with monoclonal CD-20 antibodies and other MS specific DMTs during pregnancy or within twelve months before conception and have successfully delivered a child will be included in the study. After informed consent has been received from the parents our collaborators at CMMS will extract KREC results if available from either the screening program or the preceding pilot study(17). If results are not available, the DBS samples will be retrieved and KREC analyzed specifically for this study. If the combined KREC results are ambiguous we have the option to retrieve DBS samples for all included children and perform an in-house assay developed at CMMS to confirm B-cell deficiency by determining abundance of CD19 transcripts in the sample. Furthermore, to be able to correlate B-cell deficiency to drug concentration in the child, DBS can be sent for drug level detection to our collaborators at the Haukeland University Hospital laboratory. The mothers B-cell deficiency and its consequence on immunoglobulin levels will also be assessed in the analysis.
In the prospective part of the study we plan to address if a reduction in the levels of KREC and/or CD19+ B-cells at birth of offspring to women with MS has clinical significance. Mothers with MS, regardless of treatment, that have successfully delivered or will deliver a child will be asked for informed consent included if applicable.
1. At clinical routine venous blood sampling immunoglobulin and B-cell levels are obtained. Additional samples, during clinical routine visit, in the becoming mother will allow analysis of drug concentration at the end of every trimester and 3 months post partum.
2. Within 1-12 months postpartum and after vaccination capillary blood samples from the child will be analyzed to detect antibodies induced by vaccination or infections to secure the ability to be able to develop antibodies despite being exposed to monoclonal CD20-antibodies in-utero or via breastmilk.
3. PKU-test is taken in the child within routine but additional analysis on drug levels and KREC will be analyzed as well as determining abundance of CD19 transcripts.
4. Within our routine contacts with the MS patient (mother) we will ask for infections in both, the mother and the child at 3 months and 1 year post-partum.
After informed consent has been received from the parents our collaborators at CMMS will also extract KREC results if available from the screening program. If results are not available, the DBS samples will be retrieved and KREC analyzed specifically for this study. If the combined KREC results are ambiguous we have the option to retrieve DBS samples for all included children and perform an in-house assay developed at CMMS to confirm B-cell deficiency by determining abundance of CD19 transcripts in the sample.
Primarily Rota virus vaccine will be considered because it is the earliest vaccination in the national vaccination program, offered at 6 weeks of age. Antibody levels for other vaccines or infections may be tested if deemed relevant. A detailed infectious and general medical history via the parents will be obtained at routine contacts between patient and health care and comparison of adverse outcomes between children with mothers exposed to rituximab and children to mothers with MS but without rituximab treatment within 12 months prior to conception as well as for children with and without apparent reduction in the levels of KREC and/or B-cell depletion due to in utero exposure to rituximab and children with normal KREC levels will be summarized.
In Canada, Germany and the US, breastfeeding despite receiving anti-CD20 antibody therapy is getting more common, assuming the antibody cannot be enterally absorbed hence eliminated fecally ungraded. Swedish recommendations at present are cessation of breastfeeding when starting DMT however more women choose to breastfeed regardless. We would like to offer a follow-up with breastmilk samples and blood samples in the child one month after drug application for drug level detection in breastmilk and child and B-cell level analysis in the child.
Sample analysis of B-cell levels, IgG and IgM levels as well as specific antibodies as detection for immune responds to vaccination will be analyzed with clinically established methods via the lab at Karolinska University Hospital and Lennart Svenssons lab in Linköping, Sweden. Blood sampling from the child will be performed at specialized blood sampling centers for children e.g. Karolinska university hospital. KRECs and abundance of CD19 transcripts will we analyzed in dried blood spots at CMMS with an established method within the clinics. As there is no existing established high-quality method in Sweden, we will have to send drug level analysis to the Bergen University in Norway, our collaborator. They will use ELISA and high-performance liquid chromatography-electrospray ionization mass spectrometry method to analyses drug levels in blood, breast milk and dried blood spots.
Descriptive data and differences in drug levels, cell levels, infection rate and KREC levels between women with MS who have been exposed to ant-CD20 antibodies and not close to their pregnancy and their offspring will be tested with chi2-tests or Wilcoxon rank sum test, where appropriate. IgG levels will be analyzed using a linear mixed effect model, including number of doses of administered DMT (i.e. RTX or other DMTs) as random effect, while age, sex, previous DMT, administered DMT and the interaction of doses and administered DMT as fixed effects. P-values \<0.05 will be considered statistically significant. Non-parametric variables will be presented as median (range), and normally distributed variables as mean (SD).
The dilemma of balancing the mothers need for effective treatment against potential harmful effects to the fetus is a common clinical problem. It is virtually impossible to study the effects of drugs on the developing child apart from gathering observational data from individual cases where, for any reason, the mother did receive a certain drug. In Sweden the conditions are especially good to gather information on the effects of in utero exposure to B-cell depleting drugs because the unique propensity to treat MS-patients with monoclonal CD20-antibodies (e.g. rituximab) in combination with a newborn screening program that includes a marker for B-cell deficiency. The study results will have direct impact on the clinical management of MS-patients with aggressive disease and family planning wishes.
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Multiple Sclerosis
B-Cell Deficiency
Offspring, Adult
Immunosuppression
Pregnancy Related
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
Observational Model Type
OTHER
Study Time Perspective
OTHER
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
Mother exposed to anti-CD20 ab
Mothers with MS exposed to monoclonal anti-CD20 antibody (Rituximab 500 mg iv alternatively Ofatumumab 20 mg sc or Ocrelizumab 300-600 mg iv) within 12 months before pregnancy or during pregnancy.
Anti-CD20 Monoclonal Antibody
Intervention Type
DRUG
Injection of monoclonal anti-CD20 antibody as immunomodulatory treatment of multiple sclerosis
Mother exposed to other DMT
Mothers with MS exposed to disease modifying therapy other than Rituximab, Ofatumumab or Ocrelizumab within 6 months before pregnancy
No interventions assigned to this group
Mother without DMT exposure
Mothers with MS without exposure to disease modifying therapy within 6 months before pregnancy
No interventions assigned to this group
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
Anti-CD20 Monoclonal Antibody
Injection of monoclonal anti-CD20 antibody as immunomodulatory treatment of multiple sclerosis
Intervention Type
DRUG
Other Intervention Names
Discover alternative or legacy names that may be used to describe the listed interventions across different sources.
Rituximab
Ocrelizumab
Ofatumumab
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
* Definite diagnosis of multiple sclerosis in mother AND
* Administration of Rituximab, Ocrelizumab or Ofatumumab within 12 months or during established pregnancy OR
* Administration of other immunomodulatory treatment within 12 months or during established pregnancy OR
* No administration of immunomodulatory treatment within 12 months or during established pregnancy
* Administration of Rituximab, Ocrelizumab or Ofatumumab within 12 months or during established pregnancy OR
* Administration of other immunomodulatory treatment within 12 months or during established pregnancy OR
* No administration of immunomodulatory treatment within 12 months or during established pregnancy
Exclusion Criteria
* Treatment with stem cell transfusion
Maximum Eligible Age
50 Years
Eligible Sex
ALL
Accepts Healthy Volunteers
No
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
Haukeland University Hospital
OTHER
Sponsor Role
collaborator
Region Stockholm
OTHER_GOV
Sponsor Role
lead
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Responsibility Role
SPONSOR
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
Sofia Ernestam, MD, PhD
Role: STUDY_DIRECTOR
Karolinska Institutet
Central Contacts
Reach out to these primary contacts for questions about participation or study logistics.
References
Explore related publications, articles, or registry entries linked to this study.
Ahlgren C, Oden A, Lycke J. High nationwide incidence of multiple sclerosis in Sweden. PLoS One. 2014 Sep 29;9(9):e108599. doi: 10.1371/journal.pone.0108599. eCollection 2014.
Reference Type
BACKGROUND
Bove R, Alwan S, Friedman JM, Hellwig K, Houtchens M, Koren G, Lu E, McElrath TF, Smyth P, Tremlett H, Sadovnick AD. Management of multiple sclerosis during pregnancy and the reproductive years: a systematic review. Obstet Gynecol. 2014 Dec;124(6):1157-1168. doi: 10.1097/AOG.0000000000000541.
Reference Type
BACKGROUND
Langer-Gould AM. Pregnancy and Family Planning in Multiple Sclerosis. Continuum (Minneap Minn). 2019 Jun;25(3):773-792. doi: 10.1212/CON.0000000000000745.
Reference Type
BACKGROUND
Stern J, Salih Joelsson L, Tyden T, Berglund A, Ekstrand M, Hegaard H, Aarts C, Rosenblad A, Larsson M, Kristiansson P. Is pregnancy planning associated with background characteristics and pregnancy-planning behavior? Acta Obstet Gynecol Scand. 2016 Feb;95(2):182-9. doi: 10.1111/aogs.12816. Epub 2015 Dec 8.
Reference Type
BACKGROUND
Sedgh G, Singh S, Hussain R. Intended and unintended pregnancies worldwide in 2012 and recent trends. Stud Fam Plann. 2014 Sep;45(3):301-14. doi: 10.1111/j.1728-4465.2014.00393.x.
Reference Type
BACKGROUND
Bearak J, Popinchalk A, Alkema L, Sedgh G. Global, regional, and subregional trends in unintended pregnancy and its outcomes from 1990 to 2014: estimates from a Bayesian hierarchical model. Lancet Glob Health. 2018 Apr;6(4):e380-e389. doi: 10.1016/S2214-109X(18)30029-9. Epub 2018 Mar 5.
Reference Type
BACKGROUND
Salzer J, Svenningsson R, Alping P, Novakova L, Bjorck A, Fink K, Islam-Jakobsson P, Malmestrom C, Axelsson M, Vagberg M, Sundstrom P, Lycke J, Piehl F, Svenningsson A. Rituximab in multiple sclerosis: A retrospective observational study on safety and efficacy. Neurology. 2016 Nov 15;87(20):2074-2081. doi: 10.1212/WNL.0000000000003331. Epub 2016 Oct 19.
Reference Type
BACKGROUND
Klink DT, van Elburg RM, Schreurs MW, van Well GT. Rituximab administration in third trimester of pregnancy suppresses neonatal B-cell development. Clin Dev Immunol. 2008;2008:271363. doi: 10.1155/2008/271363.
Reference Type
BACKGROUND
Kumpfel T, Thiel S, Meinl I, Ciplea AI, Bayas A, Hoffmann F, Hofstadt-van Oy U, Hoshi M, Kluge J, Ringelstein M, Aktas O, Stoppe M, Walter A, Weber MS, Ayzenberg I, Hellwig K. Anti-CD20 therapies and pregnancy in neuroimmunologic disorders: A cohort study from Germany. Neurol Neuroimmunol Neuroinflamm. 2020 Dec 17;8(1):e913. doi: 10.1212/NXI.0000000000000913. Print 2021 Jan.
Reference Type
BACKGROUND
Smith JB, Hellwig K, Fink K, Lyell DJ, Piehl F, Langer-Gould A. Rituximab, MS, and pregnancy. Neurol Neuroimmunol Neuroinflamm. 2020 May 1;7(4):e734. doi: 10.1212/NXI.0000000000000734. Print 2020 Jul.
Reference Type
BACKGROUND
Perrotta K, Kiernan E, Bandoli G, Manaster R, Chambers C. Pregnancy outcomes following maternal treatment with rituximab prior to or during pregnancy: a case series. Rheumatol Adv Pract. 2021 Jan 4;5(1):rkaa074. doi: 10.1093/rap/rkaa074. eCollection 2021.
Reference Type
BACKGROUND
Hollen C, Rice J, Park M, Yadav V. Rituximab for treatment of refractory multiple sclerosis relapses during pregnancy. Mult Scler. 2021 Sep;27(10):1620-1623. doi: 10.1177/1352458521998937. Epub 2021 Apr 30.
Reference Type
BACKGROUND
Routes JM, Grossman WJ, Verbsky J, Laessig RH, Hoffman GL, Brokopp CD, Baker MW. Statewide newborn screening for severe T-cell lymphopenia. JAMA. 2009 Dec 9;302(22):2465-70. doi: 10.1001/jama.2009.1806.
Reference Type
BACKGROUND
Borte S, von Dobeln U, Fasth A, Wang N, Janzi M, Winiarski J, Sack U, Pan-Hammarstrom Q, Borte M, Hammarstrom L. Neonatal screening for severe primary immunodeficiency diseases using high-throughput triplex real-time PCR. Blood. 2012 Mar 15;119(11):2552-5. doi: 10.1182/blood-2011-08-371021. Epub 2011 Nov 30.
Reference Type
BACKGROUND
Schrezenmeier E, Jayne D, Dorner T. Targeting B Cells and Plasma Cells in Glomerular Diseases: Translational Perspectives. J Am Soc Nephrol. 2018 Mar;29(3):741-758. doi: 10.1681/ASN.2017040367. Epub 2018 Jan 11.
Reference Type
BACKGROUND
Kruger R, Borte S, von Weizsacker K, Wahn V, Feiterna-Sperling C. Positive Kappa-Deleting Recombination Excision Circles (KREC) Newborn Screening in a Neonate With Intrauterine Exposure to Rituximab. Scand J Immunol. 2018 Jan;87(1):54-56. doi: 10.1111/sji.12627. No abstract available.
Reference Type
BACKGROUND
Barbaro M, Ohlsson A, Borte S, Jonsson S, Zetterstrom RH, King J, Winiarski J, von Dobeln U, Hammarstrom L. Newborn Screening for Severe Primary Immunodeficiency Diseases in Sweden-a 2-Year Pilot TREC and KREC Screening Study. J Clin Immunol. 2017 Jan;37(1):51-60. doi: 10.1007/s10875-016-0347-5. Epub 2016 Nov 21.
Reference Type
BACKGROUND
Serana F, Chiarini M, Zanotti C, Sottini A, Bertoli D, Bosio A, Caimi L, Imberti L. Use of V(D)J recombination excision circles to identify T- and B-cell defects and to monitor the treatment in primary and acquired immunodeficiencies. J Transl Med. 2013 May 9;11:119. doi: 10.1186/1479-5876-11-119.
Reference Type
BACKGROUND
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
142682
Identifier Type: -
Identifier Source: org_study_id