The Clinical Features and Pregnancy Outcomes of RA Patients

Recruiting

• Conditions: Pregnancy Related; Rheumatoid Arthritis
• Interventions: Drug: Prednisone; Drug: Hydroxychloroquine; Drug: CertolizumabPegol injection

• Registration Number: NCT05651373
• Lead Sponsor: Qilu Hospital of Shandong University

Brief Summary

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

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

Study Timeline

• Study Start: 2021-07-30
• Study First Submitted: 2022-11-15
• Status Verified: 2022-12
• Study First Submitted QC: 2022-12-06
• Last Update Submitted: 2022-12-06
• Study First Posted: 2022-12-15
• Last Update Posted: 2022-12-15
• Primary Completion: 2023-08-30
• Study Completion: 2024-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: Female
• Target Recruitment: 100

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

  1. Any known etiology of previous pregnancy loss

     1. Known paternal, maternal or embryonic chromosomal abnormalities.
     2. Maternal endocrine dysfunction: luteal insufficiency; polycystic ovary syndrome; premature ovarian failure (follicular phase stimulating hormone, FSH ≥ 20uU/L).
     3. Hyperprolactinemia; diabetes mellitus; other abnormalities of the hypothalamic pituitary-adrenal axis.
     4. Maternal anatomical abnormalities: uterine malformations; Asherman syndrome; cervical insufficiency; uterine fibrosis greater than 5 cm. vaginal infection.
     5. Any known serious cardiac, hepatic, renal, hematologic or endocrine disease.

  2. Any active infection, including bacterial, alisla virus (VZV), human immunodeficiency virus (HIV), human papillomavirus (HPV), syphilis, tuberculosis, fungal infections, etc.

  3. Hypersensitivity to prednisone, hydroxychloroquine, low molecular weight heparin or aspirin

  4. History of the following diseases.

     1. Past history of peptic ulcer or upper gastrointestinal bleeding.
     2. Past history of malignancy.
     3. Past history of epilepsy or mental disorder.
     4. Female has been diagnosed with SLE
     5. Women who do not consent or are unable to complete pregnancy and postpartum follow-up.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
patients using TNF inhibitor (TNFi)	CertolizumabPegol injection	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.
patients using TNF inhibitor (TNFi)	Hydroxychloroquine	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.
patients not using TNF inhibitors(TNFi)	Prednisone	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.
patients using TNF inhibitor (TNFi)	Prednisone	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.
patients not using TNF inhibitors(TNFi)	Hydroxychloroquine	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.

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Early fetal loss	within 10 weeks of gestation	Spontaneous pregnancy loss within 10 weeks of gestation
Still birth	after 10 weeks of gestation	Spontaneous pregnancy loss after 10 weeks of gestation.
Number of participants with low amniotic fluid during pregnancy	after 12 weeks of gestation	the number of participants whose B-ultrasound indicates low amniotic fluid during pregnancy
swollen joint number (SW28)	through study completion, an average of 10 months	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.
Premature rupture of membranes	after 28 weeks of gestation	the number of participants complicated with placental abruption
Eclampsia	after 20 weeks of gestation	New-onset hypertension after 20 weeks of gestation, with or without proteinuria \> 300mg/24h, with or without any organ damage with seizures
tenderness joint number (T28)	through study completion, an average of 10 months	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.
patient global assessment(PGA)	through study completion, an average of 10 months	patient global assessment(PGA)
Low-weight birth	after 28 weeks of gestation	newborns with low weight (\<2500g)
Placental abruption	after 28 weeks of gestation	the number of participants complicated with placental abruption
Gestational diabetes	through study completion, an average of 10 months	the number of participants who were diagnosed with gestational diabetes
Erythrocyte Sedimentation Rate (ESR)	through study completion, an average of 10 months	Change from Baseline in Erythrocyte Sedimentation Rate (ESR), ESR will be measured with blood samples.
Live birth rate	After 28 weeks of gestation	Percentage of all patients that lead to live birth after 28 weeks of gestation
Change from baseline Clinical Disease Activity Index (CDAI)	through study completion, an average of 10 months	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.
Percentage of patients achieving Boolean remission	through study completion, an average of 10 months	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.
Late fetal loss	after 10 weeks of gestation	Spontaneous pregnancy loss after 10 weeks of gestation
Number of participants with abnormal S / D values during pregnancy	after 12 weeks of gestation	the number of participants whose B-ultrasound indicates abnormal S / D values during pregnancy
Preterm delivery	between 28 and 37 weeks of gestation	Live birth before 37 weeks of gestation.
Fetal growth retardation (FGR)	after 12 weeks of gestation	weight below the 10th percentile for the gestational age
Number of participants with placental hematoma during pregnancy	during pregnancy	the number of participants whose B-ultrasound indicates placental hematoma during pregnancy
Gestational hypertension	through study completion, an average of 10 months	the number of participants who were diagnosed with gestational hypertension
Number of participants with placental infarction	at delivery	the number of participants whose placenta with infarction.
Change From Baseline in C-reactive Protein (CRP)	through study completion, an average of 10 months	Change from Baseline in C-reactive Protein (CRP), CRP will be measured with blood samples.
Change from baseline Simplified Disease Activity Index (SDAI)	through study completion, an average of 10 months	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.
Health Assessment Questionnaire (HAQ)	through study completion, an average of 10 months	Health Assessment Questionnaire (HAQ)

Trial Locations

Locations (1)

Qilu Hospital; 🇨🇳 Jinan, Shandong, China