Triple therapy: the patients’ perspective

5 minute read

Multiple medications might seem daunting, but patients ultimately want what’s best for them.

What’s the better treatment option for a patient with early, moderate RA who hasn’t been on DMARD therapy before?

Methotrexate alone or triple therapy using methotrexate, hydroxychloroquine and sulfasalazine? The answer depends on many factors.

As representatives of the Australian arthritis patient community, the CreakyJoints Australia team is grateful to have the opportunity to share our thoughts on the subject. However, we’d like to provide some context first.

When ANZMUSC updated their DMARD therapy guidelines for people with rheumatoid arthritis this year, the Australian rheumatology community had mixed reactions. The Australian Living Guideline for the pharmacological management of inflammatory arthritis conditionally recommends methotrexate in combination with other DMARDs (typically hydroxychloroquine and sulphasalazine) as initial therapy in people with rheumatoid arthritis.

“Hang on,” noted Associate Professor Helen Keen in her Rheumatology Republic article Triple therapy for early RA: from 2002 to 2022 and back again. “Wasn’t that the approach we used years ago? Haven’t we moved on from there?”

Professor Keen also reflected on the June 2022 online debate hosted by the Australian Rheumatology Association and presented by Helen Cooley, Ben Horgan, Lyn March and David Massasso on the subject.

In that debate, Professor Lyn March presented the argument supporting triple therapy based on the strong evidence behind it. In summary, the research indicates taking triple therapy from the start gives patients a 60% chance of achieving a 50% improvement in the number of tender/swollen joints and associated symptoms. They are also more likely to see rapid improvements in their condition.

Dr Helen Cooley took the opposing stance. She acknowledged that taking oral MTX alone may mean patients only have a 40% chance of achieving a 50% improvement. Yet, they also have a lower risk of drug interactions and side effects. Monotherapy also means patients only need to take one or two tablets a week as opposed to 35 tablets or more for triple therapy (including folate tablets).

Ben Horgan shared the consumer’s perspective for both sides of the debate. He was in a unique position to do so as he is one of the consumer representatives of the ANZMUSC Expert Advisory Guideline Development Panel.

Mr Horgan’s key message was simple. Regardless of your treatment preference, it is important to present the patient with all the current information and let them make the decision.

Mr Horgan also noted that patients will make different choices based on their needs and circumstances, so they won’t have a blanket response. Factors other than safety and efficacy might also influence their decision. For example, the cost of multiple prescriptions or the thought of taking lots of tablets each week could be scary or lead to non-compliance.

We discussed the hypothetical choice with a small cohort of our community and their responses were mixed – reflecting Ben Horgan’s points.

“If the benefits (of triple therapy) were significantly better, then I would do it,” said Naomi.

“I guess it would depend on your financial situation but I think most people would find a way to pay for three medications if they believed it would make a difference,” said Shirani.

“I’d be cautious about taking all three because I have a history with drug side effects. Having said that I would do so if recommended by my rheumatologist,” said Jo.

“The volume of tablets would have been too intimidating and I would have been fearful of side effects. I would not have been able to budget for all medications together. Of the two options in this scenario, I imagine I would have chosen the methotrexate if there were no alternatives available to me,” said Brea.

“My concern with starting with three meds is not knowing which one is causing side effects or interactions with other meds I’m on. I’d much rather start on one and add others as needed. This would decrease my anxiety about starting new meds. It would also depend on how severe my RA symptoms were at the time. The cost would be a factor. It wouldn’t stop me from taking multiple meds but when you take meds for other conditions as well it all adds up,” said Sharon.

It’s worth noting that the people we spoke with were all middle-class urban women who have had RA for years and have regular, good access to a rheumatologist.  Most of them use biologics. Therefore, they viewed the hypothetical question through the lens of extensive lived experience of the health system.

We know that when being presented with DMARD options for the first time, many RA patients are overwhelmed by information overload and very anxious about how RA will affect their lives. For them, the very idea of taking any medication can be terrifying and they may not want to take anything, let alone make a choice between treatment options.

Yet, it’s up to you, the treating doctors, to ensure you present their options in a way that empowers them to make an informed choice.

What about your patients whose RA has been stable on MTX monotherapy for years? Might they now be better off with triple therapy? They can’t choose if they don’t know their options.

With these points in mind, our request to you is that you consider the research behind the updated ANZMUSC guidelines and where appropriate to present triple therapy as an option to all your relevant patients.

Rosemary Ainley wrote this article on behalf of the CreakyJoints Australia team.

CreakyJoints Australia would like to thank Rheumatology Republic for this opportunity to share the patient voice within the Australian rheumatology community. Check us out at

You might also like to listen to Episode 4 of the CreakyJoints Australia Patient PrepRheum podcast series, Methotrexate; Management, Myths and Milestones at or on Spotify, Google Podcasts or Apple Podcasts.

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