Treatment of Rheumatoid Arthritis With DMARDs: Predictors of Response

Rheumatoid Arthritis Clinical Trial

Official title:

Treatment of Rheumatoid Arthritis With DMARDs: Predictors of Response

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03414502
• Other study ID #: 0439-23-FB
• Status: Recruiting
• Phase: Phase 3
• Start date: December 10, 2007
• Est. completion date: March 2028

Study information

• Verified date: January 2024
• Source: University of Nebraska
• Contact: Aimee B Schreiner, MS
• Phone: 402-559-4873
• Email: aischreiner[@]unmc.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a 16-week, open-label study to identify factors that help predict clinical responses to DMARD therapies for RA (Rheumatoid Arthritis) patients. All patients will receive a starting dose of DMARD medication(s) which may be adjusted by the investigator as needed. If a subject becomes intolerant to a DMARD medication the subject will be withdrawn from the study at the discretion of the investigator. Visits (prior to week 16) where withdrawal is determined to be necessary will be considered end of study. End of study data (week 16) as well as study serum will be collected. (Serum only collected on those subjects who have consented to the addendum Serum and DNA of this study). A portion of the blood collected at baseline, week 8 and week 16 with the addendum portion of the study is for future research and will be utilized attempting to look to detect the generation of superoxide radicals. The radicals have been shown to be associated with inflammation and may correlate with the progression of RA. If this is true, then treatment with RA should decrease the levels of these radicals signaling response to treatment.

Description:

The purpose of the study is to gather, in a prospective manner, information on patients with rheumatoid arthritis and their response to DMARD therapy. Specific aims of this study are:

A. To evaluate the efficacy of DMARD therapy as defined by attaining ACR 50 response after 16 weeks of therapy.

B. To identify predictors of DMARD response in patients with RA.

• Does the presence of certain genetic factors such as the shared epitope predict DMARD response

• Does the presence of serological factors (e.g. ccp (cyclic citrullinated peptide) isotypes) predict DMARD response

• Does evidence of co-morbid conditions (e.g. periodontal disease) predict DMARD response

A maximum of 400 RA patients will be consented for this protocol. Subject accrual for protocol v1.0 included UNMC (University of Nebraska Medical Center) and the RAIN (Rheumatoid Arthritis Investigational Network) sites. Subject accrual for protocol v2.0 will be derived exclusively from UNMC. Investigators have examined the discriminatory characteristics of several clinical and biologic parameters in predicting treatment response (at least 50% improvement based on ACR criteria) in initial analyses involving 54 participants with early RA treated with methotrexate monotherapy in past RAIN clinical trials. In the initial analyses, factors showing discriminatory characteristics have included rheumatoid factor (RF) isotypes (particularly IgA (Immunoglobulin A) and IgM (Immunoglobulin M), matrix metalloproteinase (MMP)-3, HLA-DRB1 (human leukocyte antigen-DR isotope) shared epitope (SE)-containing alleles, C-reactive protein, and interleukin (IL)-1. For instance, we have found that subjects with low serum concentrations of RF-IgM (< 27 IU/ml) are more likely to be non-responders than those with higher (> 27 IU/ml) serum concentrations (79% vs. 43%).

Males and females will participate in this protocol. As RA is approximately three times more common in females, it is anticipated that a higher percentage of the study subjects will be female. Subjects will be > 19 years of age. This age range was chosen because the age of majority in Nebraska is 19. RA diagnosed before the age of 19 may not have the same disease characteristics as defined by the American College of Rheumatology (ACR) criterion for RA. Pediatric subjects will not be enrolled in this study. Rheumatoid arthritis occurs in all races. No enrollment restrictions have been based on race or ethnic origin.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 400
• Est. completion date: March 2028
• Est. primary completion date: March 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 19 Years and older

Eligibility

INCLUSION CRITERIA:

• Diag. with RA with 4 of 7 ACR criteria: 1) Morning stiffness for at least 1 hr. and at least 6 wks 2) Swelling of 3 or more joints for at least 6 wks. 3) Swelling of wrist, MCP, or proximal interphalangeal joints for 6 or more wks 4) Symmetric joint swelling. 5) Hand x-rays with erosions or bony decalcifications. 6) RA nodules 7) RF positive

• >19 yrs old at time of diagnosis of RA

• Current active disease with at least1 swollen joint

• Starting new DMARD medication(s) please circle: abatacept, adalimumab, azathioprine, barcitinib, certolizumab, etanercept, golimumab, hydroxychloroquine, infliximab, leflunomide, methotrexate, minocycline, rituximab, sarilumab, sulfasalazine, tofacitinib

• If on other DMARDS, must be on stable dose for = 6 wks

• If on glucocorticoids must be on stable dose for 2 wks (< 10mg of Prednisone per day or equivalent)

• Able to adhere to study visit schedule: enrollment, 8 wks & 16 wks (+/- 2 wks)

• Hgb > 9g/dl

• WBC > 3.5

• Neutrophils > 1.0

• Platelets >100

• Creatinine <1.6

• AST or ALT not over 1.2 x upper limit

• Albumin: up to 1.0 g/dL less than lower limit of normal

EXCLUSION CRITERIA:

• Pregnant or breastfeeding women

• Men and women of child bearing potential not willing to practice successful method of contraception

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Rheumatoid Arthritis

Intervention

Drug:
• Methotrexate
Starting dose of Methotrexate of 15 mg once a week plus folic acid 1mg. daily.
• Abatacept
Starting dose which may be adjusted as needed at the discretion of the investigator
• Adalimumab
Starting dose which may be adjusted as needed at the discretion of the investigator
• Azathioprine
Starting dose which may be adjusted as needed at the discretion of the investigator
• Baricitinib
Starting dose which may be adjusted as needed at the discretion of the investigator
• Certolizumab
Starting dose which may be adjusted as needed at the discretion of the investigator
• Etanercept
Starting dose which may be adjusted as needed at the discretion of the investigator
• Golimumab
Starting dose which may be adjusted as needed at the discretion of the investigator
• Hydroxychloroquine
Starting dose which may be adjusted as needed at the discretion of the investigator
• Infliximab
Starting dose which may be adjusted as needed at the discretion of the investigator
• Leflunomide
Starting dose which may be adjusted as needed at the discretion of the investigator
• Minocycline
Starting dose which may be adjusted as needed at the discretion of the investigator
• Rituximab
Starting dose which may be adjusted as needed at the discretion of the investigator
• Sarilumab
Starting dose which may be adjusted as needed at the discretion of the investigator
• Sulfasalazine
Starting dose which may be adjusted as needed at the discretion of the investigator
• Tofacitinib
Starting dose which may be adjusted as needed at the discretion of the investigator

Locations

Country	Name	City	State
United States	University of Nebraska Medical Center	Omaha	Nebraska

Sponsors (1)

Lead Sponsor	Collaborator
University of Nebraska

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To evaluate the efficacy of DMARD therapy for Rheumatoid Arthritis as defined by attaining ACR 50 response after 16 weeks of therapy.	The ACR50 is a composite measure defined as both improvement of 50% in the number of tender and number of swollen joints, and a 50% improvement in three of the following five criteria: patient global assessment, physician global assessment, functional ability measure [most often Health Assessment Questionnaire (HAQ)], visual analog pain scale, and erythrocyte sedimentation rate or C-reactive protein (CRP).	16 weeks
Primary	To identify predictors of DMARD response in patients with RA	What are predictors of DMARD response in RA patients?	16 weeks
Secondary	Using ACR 50 composite measure, does the presence of certain genetic factors such as the shared epitope predict DMARD response	After 16 weeks of treatment, what is the number of participants with genetic factors such as the shared epitope demonstrating a 50% improvement in the number of tender and swollen joints, and a 50% improvement in three of five criteria: patient global assessment, physician global assessment, functional ability measure (most often Health Assessment Questionnaire/HAQ), visual analog pain scale and erythrocyte sedimentation rate or C-reactive protein (CRP).	16 weeks
Secondary	Using ACR 50 composite measure, does the presence of serological factors (e.g. CCP isotypes) predict DMARD response	After 16 weeks of treatment, what is the number of participants with serological factors such as CCP isotypes demonstrating a 50% improvement in the number of tender and swollen joints, and a 50% improvement in three of five criteria: patient global assessment, physician global assessment, functional ability measure (most often Health Assessment Questionnaire/HAQ), visual analog pain scale and erythrocyte sedimentation rate or C-reactive protein (CRP).	16 weeks
Secondary	Using ACR 50 composite measure, does evidence of co-morbid conditions (e.g. periodontal disease) predict DMARD response	After 16 weeks of treatment, what is the number of participants with co-morbid conditions such as periodontal disease, demonstrating a 50% improvement in the number of tender and swollen joints, and a 50% improvement in three of five criteria: patient global assessment, physician global assessment, functional ability measure (most often Health Assessment Questionnaire/HAQ), visual analog pain scale and erythrocyte sedimentation rate or C-reactive protein (CRP).	16 weeks