Biologic DMARDs have to get cheaper: here’s how


injection devicesBy Dr Irwin Lim, Rheumatologist

I felt the need to write this follow up post.

The debate about Triple Therapy vs Methotrexate (read my last post to understand it) in rheumatoid arthritis exists due to the disparity of costs.

If both are similarly effective (it’s debatable which types of patients this statement applies to), we really should be using the cheaper alternative much more.

If both were similarly priced, I don’t think we’d be having this debate. I’m guessing most rheumatologists would choose the biologic/Methotrexate combo.

Wouldn’t it be good then if the price differential reduces?

This will occur. I don’t know how quickly or how much, but these are some ways:


The rise of Biosimilars: patents for biologic DMARDs are expiring.

While these are difficult medications to copy due to their molecular size and the complexity of manufacture, there are medications being reverse engineered to look like and act like the original. Already, there are biosimilars for Infliximab, Etanercept and Rituximab.

As these enter the market, I’ve heard estimates of 30%+ reduction in price.

Use biologic DMARDs earlier in strategies that allow cessation of the biologic

We may one day be allowed to use the biologic/Methotrexate combination upfront with a plan once the rheumatoid arthritis is well controlled to then stop using the biologic and hopefully keep disease control using the cheaper medication.

The OPTIMA trial is an example of this. Rheumatoid patients with early disease (<1 year & naive to Methotrexate, and this may be a key point) were given Adalimumab/Methotrexate. After 26 weeks, roughly half of those who had good disease control had the Adalimumab stopped. At the end of the study after 78 weeks, the outcomes were similar between the group that stopped Adalimumab and the group that stayed on it.

Reduction of the dose of biologic DMARDs 

Once patients achieve good control of their disease, some rheumatologists and some patients may reduce either the amount of biologic medication being given. This leads to flare in some but in others, disease control remains good. There is limited trial data for this approach but it’s a strategy likely to be explored.

Lower dose means less costs. Less frequent administration means less costs.

The PRESERVE trial is an example of this. The patient population was different to the OPTIMA trial, with later disease, and persistent, uncontrolled disease despite Methotrexate use. Rheumatoid patients who received a low disease activity score on the Etanercept 50mg weekly/Methotrexate combination were then randomised to one of three treatment groups: 50 mg Etanercept/Methotrexate, 25 mg Etanercept/Methotrexate, or placebo/Methotrexate.

The 2 groups using Etanercept, both the conventional & the reduced dose, maintained disease control better that the Methotrexate only group. The outcomes for the 2 different doses of Etanercept were about the same.

Thanks for all the comments regarding this topic on twitter and this forum. Please do continue to share your thoughts.

Dr Irwin Lim is a rheumatologist and a director of BJC Health. You should follow him on twitter here.
Arthritis requires an integrated approach. We call this, Connected Care. Contact us.
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Triple Therapy vs Biologic/MTX: the debate rages


injection devicesBy Dr Irwin Lim, Rheumatologist

I’ve been following the American College of Rheumatology Meeting in San Diego on twitter.

There’s been a fair bit of chatter regarding the relative merits of using Triple Therapy (Methotrexate/Sulphasalazine/Hydroxychloroquine) for Rheumatoid Arthritis compared to biologic therapy/Methotrexate therapy after the failure of Methotrexate as monotherapy.

I’d previously written about the thought-provoking O’Dell paper that has reignited this debate. Read it here.

There’s no denying that biologic therapy is really very expensive. All developed countries have budgets in deficit and the money printing will have to stop sometime. Health costs are soaring and we as rheumatologists are definitely adding to the bill.

This debate counts.

And yet, I must admit I haven’t changed my practice yet.

I sit here trying to justify why this is the case to myself and the points I’ve come up with:

  • Pill Load: With triple therapy, 2 or more tablets Methotrexate weekly, at least 1-7 tablets of folic acid weekly, 4 tablets of sulphasalazine daily, 2 tablets of hydroxychloroquine daily, add in some Prednisone early in the treatment cycle, possibly calcium and vitamin D supplementation, possibly fish oil. A patient will need at least 45-50 tablets a week.
  • With the 1st point, compliance is likely to be poor. Sorry, but I find it hard to believe most of my patients will adhere to taking all these.
  • Confusion. Mine. With different medication started together, it’s harder to work out if and when a side effect occurs, which therapy to blame? To enable me to stop or modify it.
  • The baseline characteristics of the patients in the trial reported seem different from mine. The patients had late disease, at a mean of 5 years post-diagnosis. They seem older than my usual group with an age mean around 57 years.
  • The patients had been on Methotrexate as monotherapy for at least 12 weeks and were doing quite badly with a high mean DAS28 of 5.8, mean swollen joint score of 11 and mean tender joint score of 13. Our treat-to-target mantra would usually have meant some combination therapy would already have been started unless there were good reasons not to.

Now, I’m likely just justifying what I do.

I still try to treat aggressively and I still treat-to-target, seeing my Rheumatoid Arthritis patients regularly while aiming for remission or a state as close as possible to this. I use Methotrexate then add in Hydroxychloroquine and/or Salazopyrin EN early if our targets are not being met. I just don’t tend to start the whole lot as described.

And yet, I do understand the financial imperative to use cheaper drugs if possible. After all, it’s your tax dollars and it’s my tax dollars.

If I had to pay and if you had to pay (rather than our funding bodies subsidising the treatments greatly), would we do something different?

The answer I think is (maybe) yes. We would use this triple therapy regime earlier. We would justify it better. Rheumatologists would cajole more.

And maybe, I won’t need this introspective yet on-line discussion. My funding body, the government, may eventually take it out of my hands and mandate that we use triple therapy as described as part of the process to gain access to biologic medication.

These are my thoughts. What are yours?

Dr Irwin Lim is a rheumatologist and a director of BJC Health. You should follow him on twitter here.
Arthritis requires an integrated approach. We call this, Connected Care. Contact us.
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Rheumatology Webinar from my son’s room


Dylan's roomBy Dr Irwin Lim, Rheumatologist

7.30pm is a busy time at the Lim household. The kids attempting to finish some homework, the violin and piano are being practised, and there’s a general buzz as we rush around before it’s time for the kids to sleep.

On Wednesday night, I holed up in my son’s room to try and escape the bustle.

Dr Stephen Barnett from e-healthspace has been using webinars to help educate GP registrars in rural settings. He invited me to present some rheumatology.

My powerpoint slides were loaded beforehand. 10 minutes before the scheduled start, I clicked on a website link, was shown how to forward my slides and we were ready.

I sat at my son’s little desk with my laptop. Webcam turned on. Wearing my work shirt as I was being webcasted but I’d changed to shorts for comfort (I wondered what the others were wearing).

19 GPs “watched”. They interacted when I asked a question by typing their answers and comments.

It did feel a little strange, pausing and waiting for words to appear on the screen. I usually scan and try to read the faces in my audience. This wasn’t an option.

And yet, there are advantages. No travelling time. Everyone in the comfort of their own homes or clinics. An efficient way to breach the great distances in this large country. Another method of spreading the word.

Have you had experience of webinars? Either as a presenter or participant?

Dr Irwin Lim is a rheumatologist and a director of BJC Health. You should follow him on twitter here.
Arthritis requires an integrated approach. We call this, Connected Care. Contact us.
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Chronic Arthritis is often not a follow-the-textbook disease

Image courtesy of stockimages at

Image courtesy of stockimages at

By Dr Irwin Lim, Rheumatologist

I own a couple of textbooks of rheumatology, used them as references and only read a small part of these books. I’m not really a cover-to-cover type of student which seems strange to admit.

Rheumatology training was very much an apprenticeship.

You watched and mimicked. You were mentored by wiser, greyer heads.

I learned in the clinic and on the wards. Then I left the sheltered workshop.

In private practice, chronic arthritis is often not a follow-the-textbook disease:

  • Sufferers simply experience disease in many different ways
  • The range of symptoms, especially for autoimmune arthritis, can be huge
  • Patients may cope with the “same” disease in many different ways
  • Patients respond or react to the same medication in different ways

While some patients will swear that their arthritis flares with alcohol or tomatoes or gluten, there are many others who do not. While some patients note that the weather impacts their arthritis, there are many others who don’t see any pattern.

Most textbooks, and at least all the ones I read, are written by doctors.

These doctors are very good ones, and very learned but I’m not sure how much input patients may have had.

The skill as a specialist rheumatologist is not in picking the textbook case. It’s in picking the variant.

Or at least accepting that it’s not always possible to get the diagnosis right, first up.

Keeping an open mind and being happy to review and to change course is a good trait.

Was your arthritis a textbook example?

Dr Irwin Lim is a rheumatologist and a director of BJC Health. You should follow him on twitter here.
Arthritis requires an integrated approach. We call this, Connected Care. Contact us.
This blog focuses on arthritis, healthcare in general, and Connected Care. Please subscribe to keep in touch:
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Knee Pain? I prescribe diet & exercise


The following was created for an email newsletter for physiotherapists & general practitioners. I thought it was very good information so I convinced Rob Russo to allow me to post it here for you. Hope you find it useful and please do give us some feedback. I’ll use it to convince Rob to write some more! Regards, Irwin Lim

By Dr Roberto Russo, Rheumatologist

It is always a pleasure when you come across literature that supports and/or confirms your beliefs and understanding in your area of health care. This last month has seen just that in the field of Osteoarthritis.

The BMJ (British Medical Journal) and JAMA (Journal of the American Medical Association) both published articles on the effectiveness of exercise and diet in the treatment of OA affecting the lower limbs.

The first of these published in the BMJ (Uthman et al) is a systematic review and network meta-analysis focused upon the effectiveness of exercise (including all types) in relieving pain and improving function in patients with lower limb osteoarthritis.

The most interesting result I found from the sequential analysis was that by 2002, there had accumulated sufficient evidence to show a significant benefit from exercise interventions such that further trials are unlikely to overturn that conclusion.

Consequently, it seems that you can be definitive in your recommendation that patients with lower limb OA should exercise.

The question was then, which form of exercise was most beneficial?

  • In terms of pain relief, the overall best exercise intervention was a combination of aquatic exercise plus aerobic flexibility exercise, closely followed by a combination of strengthening exercises alone.
  • However, for improving function, the combination of strengthening, flexibility, and aerobic exercises performed as well as aquatic strengthening plus aerobic exercise, which were both better than other combinations of exercise.

In the article published by Messier et al, titled the IDEA study, the effect upon knee loading forces and inflammation (by measuring levels of IL-6, which is a marker of inflammation) by either dietary modification, exercise, or diet + exercise was evaluated. What they found was that:

  • Diet and exercise combined led to the greatest loss of weight (about 10% of initial body weight) and was associated with the greatest reduction in knee compressive forces and inflammation.
  • Exercise alone led to only a modest amount of weight loss (close to 2%)
  • All interventions improved pain and function, but the greatest improvements were seen in the combination group.

Their conclusion was that diet modification was the most critical factor in achieving the desired outcome, with addition of exercise augmenting the results.

A large strength of the study was that the population studied, I believe, closely resembled the cohort of patients I see in the clinic.

They included people older than 55, with a BMI between 27-41, who had mild to moderate osteoarthritis of the knee and pain on most days as a result of their disease.

Interestingly and perhaps most importantly, adherence with the treatment prescribed was around 55-70%, highlighting the greatest challenge we face in implementing this form of intervention.

Our job in some ways is in convincing all these patients to fully embrace and engage with these interventions in order to achieve the outcomes we know/promise them will follow.

I would be extremely interested to know what strategies you use to motivate your patients to commit with this form of treatment.

1. Uthman OA, van der Windt, et al. Exercise for lower limb Osteoarthritis: Systematic review incorporating trial sequential analysis and network meta-analysis. BMJ 2013; 347: f5555
2. Messier SP, Mihalko SL, et al. Effects of Intensive Diet and Exercise on Knee Joint Loads, Inflammation, and Clinical Outcomes Among Overweight and Obese Adults with Knee Osteoarthritis. JAMA 2013; 310 (12):1263-1273.

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