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Rheumatoid arthritis – virtually symptom-free thanks to modern therapies.Rheumatoid arthritis – virtually symptom-free thanks to modern therapies.

Early diagnosis and prompt, appropriate treatment are the key to successfully dealing with rheumatoid arthritis (RA). The widespread inflammatory joint disease has been around for thousands of years – but breakthroughs were only made in the 20th century. The disease can now be managed so well in more and more affected individuals that they can live with almost no symptoms.

Millennia-old bone finds and famous patients – the history of RA

Bone finds have shown that rheumatoid arthritis (RA) was around as early as 4500 BC. From then on, texts often mention diseases with symptoms matching those of RA. A famous patient in the 17th century was the Flemish painter Rubens, who often depicted hands with rheumatism in his later works. In 1859, the British doctor Alfred Baring Garrod introduced the term “rheumatoid arthritis” for the first time. At that time, treatments were limited to home remedies such as leech therapy. Medicines containing opiates and alcohol were later given to patients to provide some relief.

In the early 20th century, advances in radiology allowed RA to be more accurately diagnosed and differentiated from related conditions such as osteoarthritis. This marked the beginning of the era of modern approaches to RA – in 1941, the American Rheumatism Association recognized RA as a disease in its own right. 

As with many diseases, gold was also used for RA from the 1920s. Gold salt injections, which only develop an effect after six months, are considered to be the first generation of base medication against RA. The base medications are also called DMARDs (disease-modifying antirheumatic drugs). These show anti-inflammatory action and are therefore suitable for long-term administration in patients constantly affected by inflammation.

The year 1948 is considered a key year for rheumatology in the 20th century. In the USA, Philipp S. Hench was the first to use cortisone to treat RA. This approach changed not only rheumatology, but also medicine as a whole, thereby improving the lives of countless patients. Various synthetically produced DMARDs were ultimately approved in the 1950s, such as hydroxychloroquine, which was originally used as an antimalarial agent.

Breakthroughs in the second half of the 20th century

The 1960s and 70s were primarily characterized by new diagnostic developments, which enabled a differentiated classification of various rheumatic diseases. Further milestones in the treatment of RA followed in the 80s and 90s. Among other things, a special highlight was the development of methotrexate. As one of the synthetically produced DMARDs, the medication was adopted quickly and widely in the 80s for its targeted anti-inflammatory effects, ushering in a whole new era of RA treatment.

At the end of the 20th century, the focus was placed on the development of biologic agents. These substances interfere with the inflammatory process, for example by neutralizing proteins that transmit inflammatory signals. Biologic agents include TNF-alpha inhibitors. These drugs are characterized by their outstanding effectiveness – better response rates were achieved in patients than ever before. In the years that followed, there were various new and further developments in the field of biologic agents. These breakthroughs brought with them the hope of slower disease progression or even remission (meaning a symptom-free state defined according to certain criteria) for increasing numbers of patients.

This rapid development has also continued in the last two decades. New modes of action were identified, and corresponding medicines brought onto the market (e.g. anti-IL-6 receptor antibodies and anti-CD20 antibodies in the field of biological agents as well as JAK inhibitors from the group of synthetic basie medications). In addition, new findings allowed the strategy for the use of cortisone medications to be adapted. These continue to play a key role but can now often be administered in smaller doses.1

Thanks to breakthroughs achieved via continuous research and development, a wide range of medicines is now available. This is highly significant since the course of RA differs between patient and the appropriate treatment must therefore be determined individually. Classic pain medications (analgesics), non-steroidal anti-inflammatory drugs (NSAIDs) for pain relief and anti-inflammatory effects, and cortisone products with a strong anti-inflammatory effect are used for the treatment of RA today. The medications from these groups bring great relief to patients, but have no impact on the course of the disease. DMARDs, on the other hand, do not relieve pain, but have an anti-inflammatory effect in a wide variety of forms (conventional or synthetically produced in a targeted manner or in the form of biological agents).2

However, if RA patients are not optimally treated with medication according to the latest knowledge, they will have a shorter life expectancy, as untreated RA can also spread to organs.3 Thanks to modern RA treatment, however, it has been possible to continuously reduce the number of RA-related deaths:

RA-related deaths among 50–69-year-old women in Switzerland (source: Global Burden of Disease (GBD), https://vizhub.healthdata.org/gbd-compare/#)

RA-related deaths among 70+-year-old women in Switzerland (source: Global Burden of Disease (GBD), https://vizhub.healthdata.org/gbd-compare/#

Precision medicine: fast diagnosis and minimizing the disease burden

The medical breakthroughs of recent years have brought enormous relief for affected patients and massively reduced the disease burden. For example, data from almost 40,000 patients in Germany points to a significant reduction in the mean disease burden. The proportion of those affected with low disease activity rose to almost 50% in the reviewed period. Optimized control of the disease even has an impact on socio-economic factors: at the end of the reviewed period, the number of sick days was almost three times lower than at the beginning.4

It is estimated that about 70% of all RA sufferers could theoretically achieve remission within the first year after diagnosis. In order to achieve this high level, early diagnosis and implementation of the correct treatment are essential.5 The availability of many different medications with differing modes of action allows for treatment adjustment where necessary until the treatment objective is achieved. With a combination of the correct medication and aid measures such as physiotherapy, symptoms can be minimized and the quality of life maintained accordingly.

Precision medicine is likely to provide further advances in the treatment of rheumatoid arthritis in coming years. Genetic analyses of joint tissue, for example, will make it possible to quickly predict which medications a patient will respond to. Patients will soon no longer be divided into different groups based on clinical parameters to predict the effectiveness of medications. Instead, individual genetic signatures will enable the development of tailored treatment regimens.6 Complications from progressive RA could therefore soon be a thing of the past. 

1 Manger B. et al. (2020): 80 Meilensteine der Rheumatologie aus 80 Jahren. I-IV. Z Rheumatol.
2 Rheumaliga Schweiz (2021): Medikamente bei entzündlichem Rheuma.
3 Internisten im Netz (2017): Rheumatoide Arthritis: Prognose & Verlauf. https://www.internisten-im-netz.de/krankheiten/rheumatoide-arthritis/prognose-verlauf/#:~:text=Patienten%20mit%20rheumatoider%20Arthritis%2C%20die,um%203%2D13%20Jahre%20geringer
4 Fiehn, C. (2011): Rheumatoide Arthritis – Meilensteine für Klassifikation und Therapie. Dtsch Med Wochenschr 136: 203–205.
5 Deutsche Rheuma-Liga (2021): Rheumatische Erkrankungen: Zeit ist Remission. https://www.rheuma-liga.de/aktuelles/detailansicht/rheumatische-erkrankungen-zeit-ist-remission#:~:text=Theoretisch%20k%C3%B6nnten%20bis%20zu%2070,der%20Diagnose%20eine%20Remission%20erreichen
6 Northwestern University (2018): Rheumatoid arthritis meets precision medizine https://news.northwestern.edu/stories/2018/march/rheumatoid-arthritis-meets-precision-medicine/

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