Treatment of Pregnancy RA

Not Applicable

• Conditions: Rheumatoid Arthritis; Pregnancy Related
• Interventions: Drug: Certolizumab Pegol 200 MG/ML [Cimzia]; Drug: Hydroxychloroquine; Drug: Prednisone

• Registration Number: NCT04569890
• Lead Sponsor: RenJi Hospital

Brief Summary

It is important to control the disease of pregnant women with rheumatoid arthritis to ensure the fetal and maternal health. Frequent disease flare can increase the risk of adverse pregnancy outcomes, including abortion, premature delivery and low birth weight. However, there is no scientific and standardized treatment strategy for RA during pregnancy. About 50% of RA patients need treatment during pregnancy. Tumor necrosis inhibitor (TNFi) is an effective treatment, which can significantly improve the symptoms of RA during pregnancy. However, in order to avoid placental metastasis, TNFi is usually stopped in early pregnancy. Certolizumab pegol (CZP) is a PEGylated, Fc-free TNFi, which does not bind FcRn and is consequently not expected to undergo FcRn-mediated transfer across the placenta. Therefore, it can not transfer through placenta into FcRn and is approved to treat RA during pregnancy. This study focuses on patients with RA who consider pregnancy. We compared the efficacy, safety and economy of CZP and glucocorticoids combined with hydroxychloroquine by a randomized controlled trial.

Detailed Description

In this study, a randomized controlled study was conducted to compare the efficacy, safety and economy of CZP and glucocorticoids combined with hydroxychloroquine in the treatment of RA patients who consider pregnancy. Informed consent must be obtained for the patients to be screened.

Random method: central random.

Blinding method: assessor and data analyst blindness.

Follow-up: every 4 week.

First endpoint: 24 week.

Second endpoint: 52 week.

Safety endpoint: 24 weeks postpartum.

Missing data: core data related to treatment and disease activity are not allowed to be missing, and other data are supplemented by the last observation value.

Study Timeline

• Status Verified: 2020-09
• Study First Submitted: 2020-09-20
• Study First Submitted QC: 2020-09-24
• Last Update Submitted: 2020-09-29
• Study First Posted: 2020-09-30
• Last Update Posted: 2020-10-01
• Study Start: 2020-12-01
• Primary Completion: 2022-12-01
• Study Completion: 2023-12-01

Recruitment & Eligibility

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

Inclusion Criteria

1. A diagnosis of RA, as defined by 2010 ACR/EULAR criteria
2. DAS 28∙ESR<2.6 under the treatment of DMARDs
3. Subjects consider pregnancy, but not pregnant yet
4. Participant expects to continue CZP therapy throughout pregnancy and for at least 24 weeks postpartum
5. Participant has a negative interferon gamma release assay (IGRA) or tuberculin skin test (TST) within the prior 6 months, and there has been no change in the study participant's clinical status, or social, family, or travel history. Participants with documented Bacillus Calmette-Guérin (BCG) vaccine and at low risk for tuberculosis (TB) may enroll without having a TB test performed

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Exclusion Criteria

1. Participant has any medical or psychiatric condition that, in the opinion of the investigator, could jeopardize or would compromise the study participant's ability to participate in this study
2. Participant is not permitted to enroll into the study if she meets any of the following TB exclusion criteria:(1) Known active TB disease; (2) History of active TB involving any organ system; (3) Latent TB infection; (4) High risk of acquiring TB infection; (5) Current nontuberculous mycobacterial (NTM) infection or history of NTM infection (unless proven to be fully recovered)
3. Study participant is taking a prohibited medication or has taken a prohibited medication
4. Live vaccine(s) within 1 month prior to Screening, or plans to receive such vaccines during the study
5. Study participant has any clinically significant pregnancy-related clinical or test abnormality, as judged by the investigator
6. Study participant had a positive or indeterminate interferon gamma release assay (IGRA) or tuberculin skin test (TST) at Screening. In case of indeterminate result, a retest is allowed if time permits; 2 results of indeterminate require exclusion of the study participant

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
CZP	Certolizumab Pegol 200 MG/ML [Cimzia]	Certolizumab pegol: subcutaneous CZP at 200mg twice a week.
GC+HCQ	Hydroxychloroquine	Hydroxychloroquine: HCQ at 200mg daily, and if tolerated, escalated to 400 mg daily. Glucocorticoid: continuous usage GC at 10mg a day from Week 0 to Week 52. At 24 week, non-responders (ΔDAS28\<0.6) will switch to the other group. Participants switched to CZP group will taper their dose of GC gradually, if they have an improvement in disease activity (two successive DAS28\<2.6). If participants have a disease flare (increased DAS28\>0.6) during a reduction in corticosteroid dose, then they will resume their previous dose. Weekly step-down GC scheme: 10mg-7.5mg-5mg-2.5mg-0mg.
GC+HCQ	Prednisone	Hydroxychloroquine: HCQ at 200mg daily, and if tolerated, escalated to 400 mg daily. Glucocorticoid: continuous usage GC at 10mg a day from Week 0 to Week 52. At 24 week, non-responders (ΔDAS28\<0.6) will switch to the other group. Participants switched to CZP group will taper their dose of GC gradually, if they have an improvement in disease activity (two successive DAS28\<2.6). If participants have a disease flare (increased DAS28\>0.6) during a reduction in corticosteroid dose, then they will resume their previous dose. Weekly step-down GC scheme: 10mg-7.5mg-5mg-2.5mg-0mg.

Primary Outcome Measures

Name	Time	Method
Disease Activity	24 week	Proportion of DAS28 remission. In principle, the score of das28-esr should be used. If there is data missing, das28-crp can be used. All patients have either complete das28-esr data or complete das28-crp data.

Secondary Outcome Measures

Name	Time	Method
Time to pregnancy	52 week
ACR70	52 week	Proportion of ACR70 improvement.
ACR20	52 week	Proportion of ACR20 improvement.
ACR50	52 week	Proportion of ACR50 improvement.
Time to remission	52 week
EQ-5D	52 week	Health quality assessed by EuroQol five dimensions questionnaire. It is a preference-based measure that can be regarded as a continuous outcome scored on a -0.59 to 1.00 scale, with 1.00 indicating 'full health' and 0 representing dead.
MHAQ	52 week	The Modified Health Assessment Questionnaire (MHAQ), reduced the number of items from 20 in the original HAQ to eight, and improved the feasibility in clinical practice when screening patients. The MHAQ score is calculated as the mean of the scores for each activity. Total score is between 0.0-3.0, in 0.125 increments. Higher scores indicate worse function and greater disability. MHAQ scores \<0.3 are considered normal.
Pregnancy rate	52 week
Pregnancy outcomes	0-52 week	Pregnancy will end with live birth, stillbirth, spontaneous abortion or therapeutic abortion.

Trial Locations

Locations (1)

Renji Hospital; 🇨🇳 Shanghai, Shanghai, China