Skip to Accessibility Tools Skip to Content Skip to Footer

The Good News – Bad News About Triple Therapy

For whatever reason, I’ve lately been reading a lot about the effectiveness of triple therapy for rheumatoid arthritis. The triple-therapy study was first presented at the European League Against Rheumatism Congress 2013 and published online June 2013 in the New England Journal of Medicine to coincide with the presentation. Triple therapy, which consists of three well-established DMARDs: sulfasalazine (a sulfa drug), hydroxychloroquine (Plaquenil), and methotrexate, was shown to have comparable benefits to a combination biologic/methotrexate therapy. ( These benefits included disease measures, function, and radiographic progression. All this boils down to saying the triple-DMARD therapy worked as well as a biologic/methotrexate combination.

So, if one is as good as the other, what’s the excitement? In 2013, the triple DMARD therapy was estimated to be more than $10,000 less expensive per year than the biologic-based choice. Given the rising cost of health care, that difference has no doubt increased since then.

The good news?

Obviously the headliner is that the triple therapy is less expensive and this is a critical element for many people. Having a more cost-effective therapy that works is a dream for patients. Even with insurance and patient-assistance programs, biologics can be expensive.

Another point of good news is that the triple therapy is available in pill form. Biologics are commonly prescribed as injections or infusions which scare some people and may require visits to doctors’ offices or infusion centers. Taking a pill is much easier and doesn’t interfere with your daily routine.

Finally, there is at least the perception that biologics have a greater chance of serious side effects than DMARDs. While this may or may not be true, moving to a biologic therapy is considered by many a major step to the “big guns” for treating their RA while the older DMARDs have a longer documented history of results and side effects.

With all that good stuff, what could possibly be bad?

While I’m happy there seems to be evidence of an effective therapy, there are a few significant issues that bother me.

The first is a personal concern. That kind of savings might give insurance companies the incentive to insist on triple therapy prior to authorizing biologic therapy. In many instances there is already an insurance-dictated maze of step-therapy regulations in place for prescribing biologics. I’m afraid triple therapy may become another barrier between patients and the biologic treatment plan preferred by their doctors.

DMARDs take a long time to work. While the benefits of most biologics can be assessed after about three months, Plaquenil may not be fully effective until six months of treatment. In the study, participants were measured after a full year for effectiveness. I, for one, don’t want to wait a full year of something that isn’t working before being able to switch to a more effective treatment.

Finally is the patient’s preference for choice of therapies. When creating a treatment plan, one thing a rheumatologist considers is whether patients will prefer or comply with a single drug (monotherapy) or a combination of drugs. There is no choice when it comes to the triple-DMARD therapy. A patient must take all three drugs and this may mean up to 18 pills per day (a maximum dose would include six sulfasalazine, ten methotrexate, and two Plaquenil tablets). Compliance with this might not be as good as a simple weekly injection or monthly infusion of a biologic.

The bottom line is that it’s great that there is apparently an effective therapy using well-known, older drugs. I’m all for treatments that work regardless of the form they take including drug therapy, natural supplements, diet, exercise, or a combination thereof. If it slows down or stops RA (without also killing or maiming the patient), I’m all for it. What I don’t want is the economic or other factors somehow interfering with the doctor-patient relationship that should be primary in prescribing a treatment plan.

This article represents the opinions, thoughts, and experiences of the author; none of this content has been paid for by any advertiser. The team does not recommend or endorse any products or treatments discussed herein. Learn more about how we maintain editorial integrity here.


  • Wren moderator
    3 years ago

    Treating rheumatoid disease really is a mixed bag, isn’t it? I’ve been on triple therapy (sulfasalazine, Plaquenil, and leflunomide–my body wouldn’t tolerate MTX) since roughly 2011. The “cocktail” mostly worked, but a couple of years ago it started losing its effectiveness, and my doctor added a biologic to the three DMARDs. Today, I’m on my third biologic, as the first two didn’t work, while still taking my triple therapy cocktail. The results have been so-so.

    My point?

    Because RD affects each of us in subtly different ways, it’s notoriously difficult to treat. I’m deeply grateful that DMARDs and biologics are now available to most of us (insurance and high cost notwithstanding), since the alternative–no effective treatment at all, as it was when I was first diagnosed–is so terribly devastating. Perhaps one day there will be a truly effective, affordable, and simple treatment available to all of us, without exception.

    Thanks for another thoughtful post, Carla. 🙂

  • Carla Kienast author
    3 years ago

    Elise: Thanks for the comment and, yes, you are absolutely correct! When counting the pills, I misreported the number of MTX because they are weekly, not daily. Thanks for the clarification. I am sorry this is not working for you and that there appears to be limited options. I hope you find something that both offers relief and that is affordable. Unfortunately, too many RA patients find themselves in this situation.

  • elisee55
    3 years ago

    Thanks for the information. I have been on triple therapy but unfortunately, whilst the addition of methotrexate did result in dome limited improvements, I couldn’t tolerate the side effects. I am unable to afford biologics so at this point I’m limited in my choices. I wanted to point out that methotrexate is a once weekly regimen of either pills or self injection. Therefore daily numbers of pills are not as high as you have reported in the article. Even so, you are correct in stating that it is too many for some people…

  • Poll