Journal Club 8.15.17

We had a great first Journal Club of the year with Drs. Hunter Stone, Salahuddin Kazi (CUH), Blair Solow (PMH), Swathi Reddy and Una Makris (VA).

Hunter Stone reviewed the landmark rheumatology article published in NEJM entitled “Therapies for Active Rheumatoid Arthritis after Methotrexate Failure” which demonstrated non-inferiority of triple therapy (methotrexate + sulfasalazine + hydroxychloroquine) compared with methotrexate + etanercept for the treatment of RA after failure of MTX.


  • Biologic therapies have made RA the #8 most expensive disease!
  • Triple therapy with MTX + SSZ + HCQ is a MUCH more cost conscious than therapy with MTX + the TNF inhibitor etanercept
  • With the same amount of money you can treat 49 patients with triple therapy vs. 1 patient with MTX + etanercept


  • Based on this study, most people should demonstrate failure of triple therapy with MTX+SSZ+HCQ before moving on to biologics

Some of the questions and comments from the 3 hospitals:

  • Q: Are there any superiority trials on this currently?
    • Dr. Solow: no
  • Q: When might you go straight to TNF inhibitor despite these trial results?
    • Dr. Solow: 
      • Medical history
      • Pill burdens (lifestyle, compliance)
      • Other risk factors
      • Older guidelines say that if more joints involved said higher titer RF/CCP, you may do TNF inhibitor first, but this is removed from newer guidelines
      • Liver disease – may avoid methotrexate or leflunomide
      • Cancer history – may try triple therapy first
    • Dr. Kazi: 
      • Some patients with very HIGH disease activity (e.g., DAS score 8-9), you might want to “cool off” quickly. This way you minimize the damage that comes with continued inflammation
  • Q: What did it mean that the investigators “changed their primary endpoint?”
    • Dr. Solow:
      • May be more useful from clinic perspective to see change [in DAS28 score] over time.
      • Increased the power and this updated primary endpoint was probably OK
  • Q: If triple therapy is “non-inferior” to MTX + TNF-inhibitor, then what is the rationale for switching to MTX + TNF-inhibitor if you fail triple therapy? Would it be reasonable to say that if the triple therapy did not work, then MTX + etanercept would also not work?
    • Dr. Kazi:
      • In the trial and in clinical experience, people DO have response when you switch over after failing therapy. Though not as much as if you had started the TNF-inhibitor from the beginning, but this is also because you are selecting a population that has already demonstrated poor response to therapy


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