The Clinical Features and Pregnancy Outcomes of RA Patients

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

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.

Study Overview

• Status: Recruiting
• Conditions: Rheumatoid Arthritis; Pregnancy Related
• Intervention / Treatment: Drug: Prednisone; Drug: Hydroxychloroquine; Drug: CertolizumabPegol injection

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 Type: Observational
• Enrollment (Anticipated): 100

Contacts and Locations

• Study Contact: Name: Qiang Shu; Phone Number: 0086-0531-82169654; Email: shuqiang@sdu.edu.cn
• Study Contact Backup: Name: Bingbing Ren; Phone Number: +8618765361979; Email: sdrenbingbing@163.com

Study Locations

• China
  • Shandong
    • Jinan, Shandong, China, Shandong
      • Recruiting
      • Qilu hospital
      • Contact: Xiaoyun Yang; Phone Number: 0086-0531-82169166; Email: qlyykyc@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 43 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

• Sampling Method: Probability Sample

Study Population

female with pregnance in accordance with the diagnostic criteria of Rheumatoid arthritis in 2010.

Description

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 Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
patients not using TNF inhibitors(TNFi); 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; 5-30mg, po, once per day(Qd) prescribed if needed and adjusted due to patient response; Other Names: Pred; Drug: Hydroxychloroquine; 200mg, po, twice per day (Bid) prescribed if needed and adjusted due to patient response.; Other Names: HCQ
patients using TNF inhibitor (TNFi); 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; 5-30mg, po, once per day(Qd) prescribed if needed and adjusted due to patient response; Other Names: Pred; Drug: Hydroxychloroquine; 200mg, po, twice per day (Bid) prescribed if needed and adjusted due to patient response.; Other Names: HCQ; Drug: CertolizumabPegol injection; 200mg, iH,q2w, once two weeks (q2w) prescribed from the beginning and adjusted due to patient response.; Other Names: Cimzia

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Qilu Hospital of Shandong University
• Investigators: Study Director: Xiaoyun Yang, Qilu Hospital of Shandong University

Study record dates

Study Major Dates

• Study Start (Actual): July 30, 2021
• Primary Completion (Anticipated): August 30, 2023
• Study Completion (Anticipated): December 31, 2024

Study Registration Dates

• First Submitted: November 15, 2022
• First Submitted That Met QC Criteria: December 6, 2022
• First Posted (Estimate): December 15, 2022

Study Record Updates

• Last Update Posted (Estimate): December 15, 2022
• Last Update Submitted That Met QC Criteria: December 6, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Keywords: Rheumatoid Arthritis; Risk factors; Pregnancy outcomes; Clinical features
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Arthritis, Rheumatoid; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Anti-Inflammatory Agents; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Prednisone; Certolizumab Pegol; Hydroxychloroquine
• Other Study ID Numbers: RA with Pregnancy QiluH

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No