Biomarker-Linked Outcomes of Cellcept in Lupus Arthritis

Oklahoma Medical Research Foundation27 enrolled

Overview

We hypothesize that mycophenolate mofetil(Cellcept)is safe and effective for lupus arthritis. In this study, patients with lupus will be randomly assigned to receive mycophenolate mofetil or placebo (inert pills) for three months. At the end of three months all patients will receive mycophenolate mofetil for three additional months. The effectiveness on arthritis and other symptoms of lupus will be measured by joint counts and by the BILAG instrument (a measure of overall lupus disease activity. Additionally special blood tests aimed at understanding the biologic effects of mycophenolate mofetil will also be performed at some visits. The primary outcome measurement will be the safety and effectiveness of this treatment (as compared to placebo) at the three month point. The trial will continue in a blinded fashion (neither the investigator or the participants know who is getting mycophenolate and who is getting placebo) until 24 patients have completed the first three months of the protocol.

Patients and Methods: 27 patients with active BILAG B or A arthritis, with at least 6 swollen and 6 tender joints entered a six month study of MMF vs placebo for three months followed by open label MMF. 14 patients (12 women and 2 men) received placebo at baseline and 13 patients (11 women and 2 men) received MMF. Primary Outcome was Major Clinical Response at 3 months, then all patients received open label Cellcept for another 3 months. Blood was drawn for safety, lupus disease activity measures and exploratory Biomarkers, Joint counts were performed monthly. At baseline background DMARDs were stopped. Plaquenil was allowed. All patients received 160 mg depomedrol at baseline and were allowed 80 mg shots at subsequent months after blood draws and procedures had been completed. DEFINITION of RESPONSE Prespecified Primary Endpoint: Complete Clinical Response: BILAG C in musculoskeletal by Week 12 and decrease to 0.25 or less of tender +swollen jt counts Prespecified Secondary Endpoint: Partial response: One letter drop in musculoskeletal by Week 12 OR decrease to 0.5 or less tender + swollen jt counts Exploratory Measure (not prespecified): Major Clinical Response: BILAG C in musculoskeletal by Week 12 and decrease to 0.5 or less of tender +swollen jt counts. (In the primary analysis the one patient who met this endpoint was designated as a partial responder since those prespecified criteria were also met. Non response: Does not meet above criteria for complete or partial response Additional Measures: (prespecified secondary endpoints) included joint counts, changes in BILAG and SLEDAI and physician and patient global assessments.

Study Type

Interventions

mycophenolate mofetilDRUG

First treatment month: mycophenolate mofetil ascending doses orally Second treatment month to end of study: mycophenolate mofetil 3 gms/day (or less if tolerance issues arise)

placeboOTHER

oral placebo will be given in ascending "doses" during the first month and at full "dose" during the second and third month (or at lower "dose" if tolerance issues warrant). During the fourth month mycophenolate mofetil will be given in ascending doses to 3 gms/day (or less if tolerance issues arise) and continues until the end of the study at 6 months.

Eligibility

Sex: ALLMin age: 14 YearsMax age: 70 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Diagnosis of SLE by the 1995 modification of revised ACR criteria (includes antiphospholipid antibodies) 2. BILAG A arthritis or BILAG B arthritis with at least 6 tender and 4 swollen joints at screening and baseline 3. Stable prednisone dose at 20 mg of less for one month at baseline. 4. If on antimalarials must be stable for at least one month at baseline 5. If on NSAIDS must be on a stable regimen for at least one month but can be prn dosing 6. Must be willing to withdraw from azathioprine or MTX at the time of screening. 7. Between ages 14 and 70 8. Women of childbearing potential must have a negative pregnancy test at screening and at each month during the study. 9. All participants (male and female) must, if fertile, agree to practice contraception during the entire course of the study. This may include barrier, oral contraceptives, depo-provera, intrauterine device and/or abstinence. \- Exclusion Criteria: 1. Inability to understand informed consent 2. Drug or alcohol abuse within the past six months 3. In the opinion of the investigator, it is not likely the patient can comply with the protocol for any reason, or participation in the protocol is not in the patient's best interest. 4. Unstable medical condition that, in the opinion of the investigator would contraindicate study participation 5. History of malignancy (except for basal cell carcinoma at any time and/or cervical cancer or squamous cell cancer at least five years previous to screening). 6. Use of cyclosporine, leflunomide, cyclophosphamide or ay biologic agent within three months prior to screening. 7. Participation in any clinical study of an investigational agent within three months of screening -

Outcomes

Primary Outcomes

Arthritis Complete Response

Complete response at three months (This is defined as \</= 0.25 of the total tender plus swollen joints observed at baseline and British Isles Lupus Assessment Group (BILAG) index C (mild) or D (no longer present) score in the Musculoskeletal system), comparing treatment to placebo group as complete responder or not complete responder. This was an intent to treat analysis so dropouts were counted as non-responders.

Time frame: 3 months

Secondary Outcomes

Major Arthritis Response

This is defined as at least a 50% reduction in tender + swollen joint counts and severity rated as mild as defined by the British Isles Lupus Assessment Group Index

Time frame: 3 months

Major and Partial Clinical Response

Those meeting the Criteria for Major or Complete Clinical Response as listed in the preceding endpoints or who meet criteria for partial response defined as at least a 25% decrease in tender and swollen joint count and improvement of at least one severity rating for arthritis as at least one level on the British Isles Lupus Assessment Group Index.

Time frame: 3 Months