Treatment of Pregnancy RA

Study on the Treatment Strategy of Patients With Rheumatoid Arthritis During Pregnancy, a Randomized Control Trial in China

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Rheumatoid Arthritis; Pregnancy Related
• Intervention / Treatment: Drug: Certolizumab Pegol 200 MG/ML [Cimzia]; Drug: Hydroxychloroquine; Drug: Prednisone

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 Type: Interventional
• Enrollment (Anticipated): 100
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Le Zhang; Phone Number: +8615618296046; Email: joyce66dbl@hotmail.com

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200001
      • Renji Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 40 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: CZP; Certolizumab pegol: subcutaneous CZP at 200mg twice a week.	Drug: Certolizumab Pegol 200 MG/ML [Cimzia]; CZP 200mg twice a week subcutaneous.
ACTIVE_COMPARATOR: GC+HCQ; 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.	Drug: Hydroxychloroquine; 400mg HCQ orally daily; Drug: Prednisone; 10mg GC orally daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease Activity	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.	24 week

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ACR20	Proportion of ACR20 improvement.	52 week
ACR50	Proportion of ACR50 improvement.	52 week
ACR70	Proportion of ACR70 improvement.	52 week
Time to remission		52 week
MHAQ	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.	52 week
EQ-5D	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.	52 week
Time to pregnancy		52 week
Pregnancy rate		52 week
Pregnancy outcomes	Pregnancy will end with live birth, stillbirth, spontaneous abortion or therapeutic abortion.	0-52 week

Collaborators and Investigators

• Sponsor: RenJi Hospital
• Investigators: Study Chair: Liangjing Lu, doctor, Renji Hospital

Publications and helpful links

General Publications

• Mariette X, Forger F, Abraham B, Flynn AD, Molto A, Flipo RM, van Tubergen A, Shaughnessy L, Simpson J, Teil M, Helmer E, Wang M, Chakravarty EF. Lack of placental transfer of certolizumab pegol during pregnancy: results from CRIB, a prospective, postmarketing, pharmacokinetic study. Ann Rheum Dis. 2018 Feb;77(2):228-233. doi: 10.1136/annrheumdis-2017-212196. Epub 2017 Oct 13.
• Forger F, Zbinden A, Villiger PM. Certolizumab treatment during late pregnancy in patients with rheumatic diseases: Low drug levels in cord blood but possible risk for maternal infections. A case series of 13 patients. Joint Bone Spine. 2016 May;83(3):341-3. doi: 10.1016/j.jbspin.2015.07.004. Epub 2015 Nov 23.
• Clowse MEB, Scheuerle AE, Chambers C, Afzali A, Kimball AB, Cush JJ, Cooney M, Shaughnessy L, Vanderkelen M, Forger F. Pregnancy Outcomes After Exposure to Certolizumab Pegol: Updated Results From a Pharmacovigilance Safety Database. Arthritis Rheumatol. 2018 Sep;70(9):1399-1407. doi: 10.1002/art.40508. Epub 2018 Jul 22.

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): December 1, 2020
• Primary Completion (ANTICIPATED): December 1, 2022
• Study Completion (ANTICIPATED): December 1, 2023

Study Registration Dates

• First Submitted: September 20, 2020
• First Submitted That Met QC Criteria: September 24, 2020
• First Posted (ACTUAL): September 30, 2020

Study Record Updates

• Last Update Posted (ACTUAL): October 1, 2020
• Last Update Submitted That Met QC Criteria: September 29, 2020
• Last Verified: September 1, 2020

More Information

Terms related to this study

• Keywords: Hydroxychloroquine; Certolizumab
• 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: treatment of pregnancy RA

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: Email the researchers for details.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No