An Agency for Healthcare Research and Quality executive summary indicated that better
comparative effectiveness trial designs are needed to determine the relative merits of
existing versus new and expensive biologic drug therapies for rheumatoid arthritis (RA).
There are now 9 biologic therapies approved for treating RA. Four classes of biologics (TNF
antagonists, B-cell inhibitors, T-cell co-stimulator blocker, and Interleukin-6 receptor
blocker) are approved for use in RA patients with moderate or severe disease activity.
Several critical questions have arisen, such as 1) what therapy should be prescribed after
failure of methotrexate and/or other oral disease modifying antirheumatic drugs (DMARDs) to
adequately control disease activity; 2) what is the level of efficacy of the various biologic
therapies when compared in head-to-head trials; and 3) what are the mechanisms associated
with failure of methotrexate and/or other oral DMARD therapy and responsiveness to biologic
therapies. The MAZERATI study will provide the foundation for answering these questions and
determining the mechanisms associated with these biologic therapies.
Single center, randomized, assessor-blinded, observational longitudinal assessment. Subjects
will be randomized to treatment with an anti-TNF therapy, tocilizumab or abatacept and
evaluated at baseline, and after 1, 3 and 6 months of therapy. All biologics will be
administered subcutaneously (SQ). A blinded assessor will perform clinical disease activity
assessments and blood samples will be obtained for mechanistic studies.
After randomization, patients must take at least one dose of the assigned medication and must
maintain their baseline prednisone and oral disease modifying anti-rheumatic drug (DMARD)
medications until they have received their first dose of assigned medication to be considered
per protocol participants. During the first 3 months of therapy, patients and their
physicians will be permitted to taper but not increase corticosteroids. Adjustments of study
medication or oral DMARDs will not be permitted during the first 3 months of the study except
as outlined in the protocol. Adjustments or additions of analgesics will be permitted
throughout the study period.
Following randomization and treatment initiation, study participants will be seen in the
clinic at 1 month (3-5 weeks), 3 months (10-14 weeks), and 6 months (22-30 weeks) after the
initiation of therapy; at each time point, a blinded clinical disease activity assessment
will occur and blood samples will be obtained for mechanistic studies. The occurrence and
severity of unanticipated problems will be recorded continuously throughout the study.
- Diagnosis of RA by a physician as defined by the 1987 and/or 2010 ACR criteria.
- 18 years of age or less than or equal to 64 at the time of diagnosis of RA.
- RA Disease Activity CDAI > 10
- If using oral corticosteroids, must have been on stable dose (≤ 10 mg/day) for at
least 2 weeks prior to study drug initiation.
- PPD negative or if PPD positive documentation of therapy with INH for at least 1 month
prior to study initiation and negative chest x-ray.
- Must have been treated within the past year with either methotrexate (MTX),
leflunomide (LEF), hydrochloroquine (HCQ) and/or sulfasalazine (SSZ) for ≥ 3 months.
- Prior or concurrent use of other oral DMARD therapy, including MTX, leflunomide, SSZ,
and HCQ, is permitted. Patients taking oral DMARDs must be on stable doses of DMARDs
for at least 4 weeks prior to study drug initiation. Subjects are not required to be
taking an oral DMARD.
- Use of cyclophosphamide, penicillamine, cyclosporine A, tacrolimus or gold therapy is
not permitted in the 6 months prior to enrollment.
- Patients who are using or have used other biologic agents or tofacitinib concomitantly
or prior to this study
- History of active and/or chronic infection such as hepatitis, pneumonia,
pyelonephritis,herpetic infections or chronic skin infections and any active
opportunistic infection, including but not limited to evidence of active
cytomegalovirus, active Pneumocystis carinii, aspergillosis, histoplasmosis or
atypical mycobacterium infection.
- Active TB or evidence of latent TB (positive PPD skin test or a history of old or
latent TB on chest x-ray) without adequate therapy for TB.
- Pregnant or lactating women.
- Patients with current signs or symptoms of uncontrolled renal, gastrointestinal,
endocrine, pulmonary, cardiac, neurologic or cerebral disease.
- Diagnosis of liver disease or elevated hepatic enzymes, as defined by ALT, AST or both
>1.5 x the upper limit of normal (ULN) or total bilirubin > ULN.
- Any of the following hematologic abnormalities, confirmed by repeat tests:
1. White blood count < 3,000/µL or > 14,000/µL
2. Lymphocyte count <500/µL
3. Platelet count < 100,000/µL
4. Hemoglobin < 8.0 g/dL
5. Neutrophil count < 2,000 cells/µL
- Major surgery (including joint surgery) within 8 weeks prior to screening or planned
major surgery within 6 months following randomization.
- Immunization with a live/attenuated vaccine within 2 months prior to baseline or 3
months of last study visit.
- History of severe allergic or anaphylactic reactions to human, humanized, or murine
- History of other malignancy within 5 years prior to screening, except for
appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, or
Stage I uterine cancer
- Patients with reproductive potential not willing to use an effective method of
- History of alcohol, drug or chemical abuse with 1 year prior to screening