Clinical trial NCT04569890: Treatment of Pregnancy RA
Official title: Study on the Treatment Strategy of Patients With Rheumatoid Arthritis During Pregnancy, a Randomized Control Trial in China
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Rheumatoid Arthritis
Pregnancy Related
Keywords: Certolizumab
Hydroxychloroquine
Lead sponsor: RenJi Hospital
Sponsor class: OTHER
First posted: 2020-09-30
Enrollment: 100
Sex: FEMALE
Minimum age (years): 20
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Central random. Statistical experts from a third-party company not involved in the study will generate a random number table by computer system. The patients will be numbered according to their visiting order, and 1:1 allocated according to the random data table.
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Disease Activity
timeFrame: 24 week
Secondary outcomes:
measure: ACR20
timeFrame: 52 week
measure: ACR50
timeFrame: 52 week
measure: ACR70
timeFrame: 52 week
measure: Time to remission
timeFrame: 52 week
measure: MHAQ
timeFrame: 52 week
measure: EQ-5D
timeFrame: 52 week
measure: Time to pregnancy
timeFrame: 52 week
measure: Pregnancy rate
timeFrame: 52 week
measure: Pregnancy outcomes
timeFrame: 0-52 week
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Renji Hospital
state: Shanghai
Study officials:
affiliation: RenJi Hospital
name: Liangjing Lu, doctor
role: STUDY_CHAIR
References:
citation: 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.
citation: 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.
citation: 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.