Treating Rheumatoid Arthritis: What Is Triple Therapy?

Treating Rheumatoid Arthritis: The Facts About Triple Therapy

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  • Treatment Options for RA

    Treatment Options for RA

    After a rheumatoid arthritis (RA) diagnosis, your doctor and rheumatologist will work with you to reduce painful symptoms and slow the progression of the disease.

    Medication is often the first line of treatment for RA. Drugs include:

    • nonsteroidal anti-inflammatory drugs (NSAIDs)
    • corticosteroids
    • disease-modifying antirheumatic drugs (DMARDS)
    • biologic agents

    Some doctors will administer a combination of drug therapies, depending on symptoms and stage of the disease.

    Discuss your medication options with your doctor to determine the best course of treatment.

  • Types of DMARDs

    Types of DMARDs

    Newly diagnosed patients with RA will likely receive a prescription for a DMARD such as:

    • methotrexate
    • hydroxychloroquine
    • leflunomide
    • sulfasalazine

    In the past, doctors typically started patients off with aspirin or nonsteroidal anti-inflammatory drugs to reduce pain and inflammation. Now, many doctors treat patients more aggressively and prevent joint damage with a DMARD.

    Two other categories of DMARDs used to treat RA are biologic response modifiers and jak kinase. Biologics such as etanercept block tumor necrosis factor (TNF), which triggers inflammation.

    A new category called jak kinase (JAK) inhibitors fights inflammation within the cells. Tofacitinib is an example of a JAK inhibitor.

  • The TEAR Study

    The TEAR Study

    With so many drug options, healthcare providers will work with patients to determine the best combination of therapy to treat RA.

    Arthritis researcher Larry W. Moreland, M.D., chief of the Division of Rheumatology and Clinical Immunology at the University of Pittsburgh, studied oral triple therapy along with 40 collaborators. They reported their findings in Arthritis & Rheumatism in September 2012.

    Their study looked at treatment of early aggressive RA over two years. The study became known by its acronym: the TEAR study.

  • TEAR Study Goals and Results

    TEAR Study Goals and Results

    The patients received one of four treatments:

    • initial treatment with methotrexate (MTX), plus etanercept
    • initial treatment with oral triple therapy: MTX, sulfasalazine, and hydroxychloroquine
    • a step up from initial MTX monotherapy to one of the above combination therapies
    • placebos

    The Moreland group reported that either of the first two treatments worked more effectively than MTX monotherapy.

  • The O’Dell Study

    The O’Dell Study

    James R. O’Dell, M.D., chief of rheumatology at the University of Nebraska Medical Center in Omaha, has authored numerous studies of RA over the decades. O’Dell was also a co-author on the TEAR study.

    The New England Journal of Medicine (NEJM) published the results of a 48-week study of 353 RA patients in July, 2013. Numerous co-authors joined O’Dell in a multinational effort.

  • O’Dell Results

    O’Dell Results

    All the patients in the O’Dell study had active RA, despite earlier treatment with MTX. Investigators assigned treatment randomly: either triple therapy with MTX, sulfasalazine, and hydroxychloroquine, or etanercept plus MTX. Patients who failed to demonstrate improvement at 24 weeks were switched to the other group.

    Both groups recorded significant improvement, the NEJM article reports. Twenty-seven percent of patients in each group required switching. O’Dell and colleagues reported no significant differences in pain or quality of life. They concluded the results were about the same for each approach.

  • Cost Considerations

    Cost Considerations

    MTX, sulfasalazine, and hydroxychloroquine are all older drugs. They provide a relatively inexpensive treatment option. Combining MTX with etanercept, a biologic that combines Enbrel and Immunex, is more expensive.

    O’Dell told the European League Against Rheumatism Congress 2013 that while the two strategies provide comparable benefits, triple therapy is $10,200 cheaper per patient a year.

    Starting off patients with triple therapy made economic sense, O’Dell concluded. He suggested that patients with an unsatisfactory response switch to MTX and etanercept.

  • Work Time Results

    Work Time Results

    Dutch researchers also give a thumbs-up to triple therapy for lowering both direct and indirect costs. They reported on 281 patients with newly diagnosed RA in October 2013. The patients participated in a Rotterdam study called tREACH.

    Those on triple therapy required less costly treatment. This is in part because they didn’t require costly biologicals to augment MTX.  They also missed less work due to being sick.


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