Recently-published research conducted at The University of Manchester has revealed a potential link between certain treatments for Rheumatoid Arthritis and significantly reducing the risk of heart attacks in patients with the disease. Professor Kimme Hyrich explains how this new discovery may be the start of a treatment policy shift that could ultimately save thousands of lives.

• Rheumatoid arthritis is treated with different drugs at different levels of severity
• Study has shown an almost 40 per cent reduction in heart attack risk in patients using ‘Biologic Drugs’ treatments
• Revising treatment guidelines would be “a significant step towards saving lives”

Rheumatoid arthritis (RA) is a debilitating condition, causing long-term pain, stiffness, and swelling of joints, particularly the hands, wrists and feet, especially if effective treatment is not received. A further complication for sufferers of RA is that patients with the condition have a 60 per cent higher risk of heart attacks.

It is thought that the inflammation caused by RA may be the key factor behind this increased risk, and research is growing that control of inflammation in the joints of rheumatoid arthritis patients could significantly reduce their risk of heart attacks.

Whilst most RA treatments aim to reduce inflammation, our research forms part of a growing body of evidence that shows some treatments may be significantly more effective than others. Across Europe, the mainstay of therapy for RA is a type of drug known as DMARD (or disease modifying anti-rheumatic drug). Unfortunately, not all patients will respond to DMARDs and if their arthritis is very active, they will move onto a type of drug known as biologics and in particular a specific type of biologic referred to as TNFi (or, ‘tumour necrosis factor inhibitor’) which works by reducing and, in some cases, eliminating the proteins that cause joint swelling to take place.

As part of the Arthritis Research UK Centre for Epidemiology, based at The University of Manchester, I have been part of a research team studying the effects of biologic drugs on arthritic inflammation and heart attack risk. Recently we compared the risk of heart attack between UK patients with RA who received TNFi biologics and those who received DMARD therapy only.

Our Project

Our study, which was funded and supported by the British Society for Rheumatology, has followed more than 14 thousand patients receiving either TNFi or DMARDs. We tracked their symptoms and their progress, including the incidence and the severity of any heart attacks suffered over the first 3-5 years in the study. The results showed that the risk of heart attacks for patients being treated with TNFi drugs was almost 40 per cent lower than in the DMARD-only group. This was true even after we allowed for some differences in heart attack risk between the patients in the 2 groups.

Challenging current treatment restrictions

Rheumatoid arthritis patients already have to endure a debilitating condition, but to have an elevated risk of heart attacks because of their disease is a very worrying complication. In addition to managing risk factors such as high blood pressure and high cholesterol, achieving excellent control of inflammation can also reduce this risk. Less inflammation may delay or slow the accumulation and progression of plaque (“atherosclerosis”) leading to fewer heart attacks. Although our recent observational study cannot pinpoint the exact reason why patients receiving TNFi had fewer heart attacks, one hypothesis is that patients who received TNFi had better control of RA inflammation.

Currently the use of TNFi in the UK is restricted by the National Institute for Clinical Excellence (NICE) to those patients who have high levels of “disease activity” despite treatment with at least 2 DMARDs. This is one of the most restrictive eligibility criteria for TNFi in Europe. NICE is responsible for recommending which treatments can be made available to patients in the National Health Service (NHS). However, not all patients will need a TNFi, as in a majority of patients DMARDs are an excellent treatment for RA, which result in remission of the arthritis. TNFi are very expensive, thousands of pounds a year, so for the NHS, controlling access to expensive therapies when there are less expensive and very effective alternative therapies makes complete sense. However, not all patients achieve remission with DMARDs only. Those that have persistent high disease activity will qualify for TNFi but those who have what we call moderate or have low-grade grumbling inflammation do not. These patients also have ongoing pain and stiffness in their joints and we know that biologics are also effective in this group of patients. It is very likely the risk of future heart attack in these patients is also increased. Ideally, all patients with ongoing inflammation despite DMARDs, whether there disease activity is “high” or “moderate” should have access to a biologic, and the possibility that side effects will be reduced by this treatment adds weight to this argument.

“A significant step towards saving lives”

This result alone won’t change NICE policy, which tends to grant access to high costs drugs based on effectiveness in treating the disease itself, rather than on consideration of added benefits such as other disease prevention. However in most cases,  the current way that NHS costs are determined for new and expensive drugs do not take into account the costs of treating adverse events and therefore preventing heart attacks is not considered. Therefore, NICE should look wider and consider all of the potential benefits of treatments, not only treatment of the underlying disease. They should also consider further the risk of not treating patients with less severe but still persistent and symptomatic disease. Our group continues to look at outcomes among patients with “moderate” RA to build weight to this argument.

In policy terms, there are a number of things that could help build momentum behind this exciting new research:

• We need more research to help us understand our research findings and this may mean more laboratory or basic research. Is this a specific effect of TNFi, which would have wide-ranging implications and benefits, even outside of RA perhaps, or is it a direct effect of inflammation control, regardless of which medicine is used?
• NICE should continue to be pushed to consider the use of biologics in patients with lesser but important levels of disease activity, especially as evidence in this area continues to grow and show the benefits in these patients
• NICE should consider wider measures of treatment effectiveness in their assessments, such as prevention of comorbidity such as heart attacks. Unfortunately when drugs are first licensed this type of information may not be available, but as it does become available, guidelines should be revisited and updated. This may need a lead from government, but being able to cost and consider future harm mitigation whilst deciding on treatment guidelines would be a quantum leap forward for our health services.

Our study is potentially a significant step towards saving lives, and shows the value in institutions like The University of Manchester taking a lead in shaping our medical research agenda. It also shows the tremendous strength of an organisation such as the British Society for Rheumatology for bringing its members together to contribute to and support such a large scale and intensive study such as this.

With that said, it will still need more research, and more engagement from regulators and law-makers before the full potential of our findings can be realised for the patients and the families of sufferers from this terrible disease.

You can read the full report on our research online in the latest edition of The Annals of Rheumatic Disease