The Clinical Features and Pregnancy Outcomes of RA Patients

Study Overview
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Brief Summary
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This study includes RA patients in pregnancy, who are using different treatment regimens，including prednisone, hydroxychloroquine, and/or TNF inhibitors. The maternal disease activity, pregnancy outcomes, maternal and fetal safety are assessing during the trimester of pregnancy. The effects of different therapies and risk factors for adverse pregnancy outcomes will be analysis.

Detailed Description
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To study the risk factors of poor pregnancy outcomes in RA patients, and evaluate impact of different therapies on the maternal and fetal health. The follow-up study will be scheduled every 4 weeks from confirmed pregnancy until delivery, records the disease activity of RA, pregnancy outcome and safety with the help of the smart disease management system (SSDM) and face-to-face consultations. The effects of different therapies on maternal and fetal will be valued

Official Title
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The Clinical Features and Pregnancy Outcomes of Patients With Rheumatoid Arthritis :a Prospective Cohort Study

Conditions
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Rheumatoid Arthritis, Pregnancy Related

Intervention / Treatment
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* Drug: Prednisone
* Drug: Hydroxychloroquine
* Drug: CertolizumabPegol injection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: - 1.Age between 20 and 45 years old. 2.Diagnosis of RA: Approved by the American College of Rheumatology and the European League Against Rheumatism in 2010. Involved joints 1 large joint (0 points) 2-10 large joints (1 point) 1-3 small joints (with or without large joints) (2 points) 4-10 small joints (with or without large joints) (3 points) more than 10 small joints (at least one small joint) (5 points) Serological indicators RF and ACPA negative (0 points) RF and ACPA, at least one of which is low titer positive. (2 points) RF and ACPA with at least one high titer positive (3 points) Acute chronotropic reactants Both CRP and ESR normal (0 points) Abnormal CRP or ESR (1 point) Duration of synovitis <6 weeks (0 points) ≥6 weeks (1 point) 3.Voluntary participation in this study, willingness to administer medication and follow up according to the treatment plan, and signing of an informed consent form. Exclusion Criteria: Women who meet any of the following criteria will be excluded from the study Any known etiology of previous pregnancy loss Known paternal, maternal or embryonic chromosomal abnormalities. Maternal endocrine dysfunction: luteal insufficiency; polycystic ovary syndrome; premature ovarian failure (follicular phase stimulating hormone, FSH ≥ 20uU/L). Hyperprolactinemia; diabetes mellitus; other abnormalities of the hypothalamic pituitary-adrenal axis. Maternal anatomical abnormalities: uterine malformations; Asherman syndrome; cervical insufficiency; uterine fibrosis greater than 5 cm. vaginal infection. Any known serious cardiac, hepatic, renal, hematologic or endocrine disease. Any active infection, including bacterial, alisla virus (VZV), human immunodeficiency virus (HIV), human papillomavirus (HPV), syphilis, tuberculosis, fungal infections, etc. Hypersensitivity to prednisone, hydroxychloroquine, low molecular weight heparin or aspirin History of the following diseases. Past history of peptic ulcer or upper gastrointestinal bleeding. Past history of malignancy. Past history of epilepsy or mental disorder. Female has been diagnosed with SLE Women who do not consent or are unable to complete pregnancy and postpartum follow-up.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| patients not using TNF inhibitors(TNFi)<br>The cohort includes the RA patients in pregnancy. Drug: Hydroxychloroquine(HCQ)，200mg, po, twice per day (Bid) prescribed at the beginning and adjusted due to patient response. Drug: Prednisone(Pred)，5-30mg, po, once per day (qd) prescribed at the beginning and adjusted due to patient response. | Drug: Prednisone<br>* 5-30mg, po, once per day(Qd) prescribed if needed and adjusted due to patient response<br>* Other names: Pred;Drug: Hydroxychloroquine<br>* 200mg, po, twice per day (Bid) prescribed if needed and adjusted due to patient response.<br>* Other names: HCQ;|
| patients using TNF inhibitor (TNFi)<br>The cohort includes the RA patients in pregnancy. Drug: Hydroxychloroquine(HCQ)，200mg, po, twice per day (Bid) prescribed at the beginning and adjusted due to patient response. Drug: Prednisone(Pred)，5-30mg, po, once per day (qd) prescribed at the beginning and adjusted due to patient response. Drug: TNFi ,such as Certolizumab Pegol (Cimzia)，200mg, iH,q2w, once two weeks (q2w) prescribed from the beginning and adjusted due to patient response. | Drug: Prednisone<br>* 5-30mg, po, once per day(Qd) prescribed if needed and adjusted due to patient response<br>* Other names: Pred;Drug: Hydroxychloroquine<br>* 200mg, po, twice per day (Bid) prescribed if needed and adjusted due to patient response.<br>* Other names: HCQ;Drug: CertolizumabPegol injection<br>* 200mg, iH,q2w, once two weeks (q2w) prescribed from the beginning and adjusted due to patient response.<br>* Other names: Cimzia;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The percentage of patients who achieve clinical remission using DAS28-CRP | The percentage of patients whose DAS28 achieve remission（DAS28-CRP≤ 2.6）and Low Disease Activity (DAS28-CRP ≤3.2) . | through study completion, an average of 10 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Early fetal loss | Spontaneous pregnancy loss within 10 weeks of gestation | within 10 weeks of gestation | 
| Late fetal loss | Spontaneous pregnancy loss after 10 weeks of gestation | after 10 weeks of gestation | 
| Still birth | Spontaneous pregnancy loss after 10 weeks of gestation. | after 10 weeks of gestation | 
| Preterm delivery | Live birth before 37 weeks of gestation. | between 28 and 37 weeks of gestation | 
| Low-weight birth | newborns with low weight (<2500g) | after 28 weeks of gestation | 
| Premature rupture of membranes | the number of participants complicated with placental abruption | after 28 weeks of gestation | 
| Placental abruption | the number of participants complicated with placental abruption | after 28 weeks of gestation | 
| Fetal growth retardation (FGR) | weight below the 10th percentile for the gestational age | after 12 weeks of gestation | 
| Number of participants with low amniotic fluid during pregnancy | the number of participants whose B-ultrasound indicates low amniotic fluid during pregnancy | after 12 weeks of gestation | 
| Number of participants with abnormal S / D values during pregnancy | the number of participants whose B-ultrasound indicates abnormal S / D values during pregnancy | after 12 weeks of gestation | 
| Number of participants with placental hematoma during pregnancy | the number of participants whose B-ultrasound indicates placental hematoma during pregnancy | during pregnancy | 
| Eclampsia | New-onset hypertension after 20 weeks of gestation, with or without proteinuria > 300mg/24h, with or without any organ damage with seizures | after 20 weeks of gestation | 
| Gestational diabetes | the number of participants who were diagnosed with gestational diabetes | through study completion, an average of 10 months | 
| Gestational hypertension | the number of participants who were diagnosed with gestational hypertension | through study completion, an average of 10 months | 
| Number of participants with placental infarction | the number of participants whose placenta with infarction. | at delivery | 
| Change From Baseline in C-reactive Protein (CRP) | Change from Baseline in C-reactive Protein (CRP), CRP will be measured with blood samples. | through study completion, an average of 10 months | 
| Erythrocyte Sedimentation Rate (ESR) | Change from Baseline in Erythrocyte Sedimentation Rate (ESR), ESR will be measured with blood samples. | through study completion, an average of 10 months | 
| Live birth rate | Percentage of all patients that lead to live birth after 28 weeks of gestation | After 28 weeks of gestation | 
| Change from baseline Simplified Disease Activity Index (SDAI) | SDAI score exceeding 26 is considered high disease activity; 11 <SDAI ≤26，moderate disease activity; 3.3 <SDAI ≤11, low disease activity; remission is SDAI score ≤ 3.3. | through study completion, an average of 10 months | 
| Change from baseline Clinical Disease Activity Index (CDAI) | CDAI > 22 is considered high disease activity; 10 <CDAI ≤ 22, moderate disease activity; 2.8 <CDAI ≤10, low disease activity; remission is CDAI score ≤2.8. | through study completion, an average of 10 months | 
| swollen joint number (SW28) | SW28 means the number of joints with swelling counted in 28 synovial joints, including proximal interphalangeal joints (10 joints), metacarpophalangeal joints (10), wrists (2), elbows (2), shoulders (2) and knees (2) bilateral. | through study completion, an average of 10 months | 
| tenderness joint number (T28) | T28 means the number of joints with tenderness upon touching counted in 28 synovial joints, including proximal interphalangeal joints (10 joints), metacarpophalangeal joints (10), wrists (2), elbows (2), shoulders (2) and knees (2) bilateral. | through study completion, an average of 10 months | 
| patient global assessment(PGA) | patient global assessment(PGA) | through study completion, an average of 10 months | 
| Health Assessment Questionnaire (HAQ) | Health Assessment Questionnaire (HAQ) | through study completion, an average of 10 months | 
| Percentage of patients achieving Boolean remission | Clinical remission was defined when the number of swollen joints ≤1, the number of painful joints ≤1, CRP ≤1 mg/dl and the patient's overall score of the disease ≤1 were also satisfied. | through study completion, an average of 10 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Rheumatoid Arthritis, Pregnancy outcomes, Clinical features, Risk factors