26 July 2019

Another great decade, but there’s more to do

Clinical Rheumatology

The past decade has brought a wealth of innovation in arthritis therapies. 

Many newer medications have been able to dramatically improve symptoms in patients suffering from inflammatory autoimmune arthritis, such as rheumatoid arthritis, ankylosing spondylitis, juvenile idiopathic arthritis and psoriatic arthritis.

Some have even been able to lower symptoms to such an extent that patients enter remission or, at least, the medications reduce the activity of the inflammatory arthritis to low levels, outcomes which would have been thought highly unlikely two decades ago.

Let me use the example of rheumatoid arthritis to help demonstrate how therapy has changed.

All of you reading this would be familiar with the use of non-steroidal anti-inflammatory drugs (NSAIDs), cyclooxygenase-2 (Cox- 2) inhibitors and corticosteroids. These anti-inflammatory drugs may reduce symptoms fast, usually within just a few days of use, in a proportion of patients.

These drugs while potentially effective in controlling symptoms, do not necessarily prevent the destruction of joints, which is a major goal of therapy and something we need to slow down as much as possible.

CONVENTIONAL DMARDs

If the diagnosis is clear-cut, you will find that rheumatologists will commence conventional synthetic disease-modifying anti-rheumatic drugs (DMARDs) soon after diagnosis. Conventional DMARDs include methotrexate, sulphasalazine, hydroxychloroquine, leflunomide, azathioprine, gold, and cyclosporin.

Each of these medications has their own benefits and side-effects. All of them will require close monitoring, at least in the initial stages of management.

The most widely used conventional synthetic DMARDs in rheumatoid arthritis would be methotrexate, sulphasalazine, leflunomide and hydroxychloroquine.

Methotrexate is typically the most commonly used DMARD, given it has good efficacy and relative safety in the low doses used in rheumatic disease.

The rheumatologist would assess disease activity regularly, and either add to or change the medications accordingly until therapeutic goals are met, with these goals ideally previously agreed to by both patient and doctor. With the various tiers of rheumatoid treatment options, there’s usually another medication to try if something is not working effectively enough.

Less than 50% of patients are treated with just one of these medications. More commonly, we will need to prescribe a combination of different DMARDs in order to optimise control of rheumatoid arthritis. 

Very few rheumatologists would be using azathioprine, gold or cyclosporin for rheumatoid arthritis these days given the poorer risk and benefit balance of these medications and the fact that there are much better alternatives.

With the new group of biologic and targeted synthetic DMARDs available, few rheumatologists linger on the older generation drugs once it is clear remission or, at least, a very low level of disease activity, cannot be attained using these conventional DMARDs.

BIOLOGIC DMARDs

For the past 20 years, a number of more sophisticated medications have been made to target specific cytokines involved in autoimmunity. These drugs are referred to as the biologic DMARDs.

They’re engineered within biologically-active cell systems to have highly specific effects on cytokines and/or their receptors. If combination therapy with the conventional DMARDs does not provide sufficient control of disease, biologic DMARDs need to be considered.

Biologic DMARDs (i.e. adalimumab, etanercept, infliximab, golimumab, certolizumab, abatacept, rituximab and tocilizumab) are more powerful immunosuppressants and are given as either subcutaneous injections or regular infusions through veins. They are highly effective in lowering the symptoms, the joint damage and deformity involved with rheumatoid arthritis. 

TARGETED SYNTHETIC DMARDs

In the last couple of years, powerful oral medications have been developed. These small molecule medications are distinct from the very large molecule biologic DMARD medications in how they work. They inhibit proteins called janus kinases, to then disrupt cell-signalling processes and alter the mix of cytokines.

These JAK inhibitors are taken orally rather than as injections, and for some patients, this is most convenient.

JAK inhibitors approved for use in Australia are tofacitinib and baricitinib. 

NEW GOALS

Since 2004, Australians have had good access to these advanced DMARD medications, with the high costs heavily subsidised by our PBS system. This has clearly helped rheumatologists achieve much better outcomes for people with the disease.

However, I need to give some balance to this discussion. These advanced DMARDs are not right for some patients due to the side-effect profile. And while these medications are tremendous advances, they are very costly, with access, by necessity, limited by some stringent PBS-derived criteria to save our tax dollars.

Importantly, the ability to access these medications has inspired a change in attitude and practice, leading to some shifting of goalposts.

These changes and new goals include:

  • As we have more effective agents which patients can only access after meeting certain criteria, we have actually learned to use our older therapies (e.g. methotrexate) much more wisely and effectively as we seek to test these criteria.
  • We tolerate less. Less damage, less loss of ability to perform daily activities. I would routinely ask a patient what they still can’t do that they would like to, and we strive to achieve those goals.
  • “With great power, comes great responsibility.” Rheumatologists now need to work to increase awareness of these inflammatory diseases (as well as all the other rheumatic diseases which tend to be neglected). Effective treatment is still being deprived due to a lack of awareness among patients and their treating practitioners.
  • In rheumatoid arthritis, time-to-rheumatologist is clearly a modifiable factor and greatly influences long-term outcomes. We have learned that we need better ways to reduce the time for patients to present to their caring GPs, and then reduce the time and access block for GPs to refer to the rheumatologist once there is suspicion of an inflammatory arthritis, and then reduce the time waiting to see the rheumatologist given workforce shortages andAustralia’s geographical issues.
  • These medications do not help everyone, however, and one “Holy Grail” in rheumatology continues to be the need to be more precise in how we work out which medication is the right one for each individual patient, preferably at the correct time in their disease course to make the most difference with the least issues.

It’s an exciting time for rheumatologists. I think we all feel more potent, and there is more to come. Scientific endeavour has upscaled, with new therapies and understanding around the corner in a gamut of different diseases that are classified as rheumatic.

Still, we should not forget the simple things: 

  • Disease awareness
  • Patient education
  • Improved communication with our GP colleagues
  • Improved processes to help workflow
  • Listening to the person we’re trying to help

Dr Irwin Lim is a Sydney-based rheumatologist and director of BJC Health. Dr Lim is also editor of The Medical Republic’s sister publication, Rheumatology Republic

BJC Health’s JAM Session is designed to facilitiate training in musculoskeletal disease for GPs. The next JAM Session is being held in Sydney at the University of Technology on  August 3 and is free to attend.

To register go to: bjchealthjam.com.au