Is it possible to understand who is at risk of developing rheumatoid arthritis and try to prevent it in these people? Two studies just published in the Lancet demonstrate that it can be done, moreover using a drug already available for these patients. However, the challenge can only be overcome by understanding who the people are who are destined to develop the disease and who can therefore benefit from treatment at a very early stage. To do this, you can look at some specific indicators, such as anti-citrulline antibodies (ACPA-positive) or the presence of persistent joint pain, and also use imaging tools. One of these, used in one of the two published studies, was developed by Maria Antonietta D’Agostino, director of the Rheumatology Unit of Fondazione Policlinico Universitario Agostino Gemelli IRCCS and Professor of Rheumatology at the Catholic University. It is called OMERACT-EULAR and it is a score that, starting from a joint ultrasound, is able to quantify the characteristic inflammation of this autoimmune disease even in the very early stages in patients who have no clinical signs.
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A window that must be exploited
Identifying the disease before symptoms are evident is a challenge that, if met, brings a real benefit to patients. “Rheumatoid arthritis – explains D’Agostino – is a very disabling disease which at its onset does not give obvious clinical signs; in the very early stages, non-specific symptoms such as joint pain appear, but the key signs of the disease, such as inflammation, are absent. These patients, although considered at risk, having no obvious disease, are not treated with immunosuppressive drugs. However, in this phase of the disease there is a window of therapeutic opportunity and early treatment of these patients could avoid the appearance of more serious symptoms or even slow the onset of the full-blown disease.”
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In both studies published in the Lancet, these ‘very early’ patients were divided into two groups, the first received abatacept – a biological drug that blocks the activation of T lymphocytes, responsible for the inflammatory cascade that leads to the full-blown disease -, the other a placebo. The results showed a reduction in the manifestations of full-blown rheumatoid arthritis in patients treated with the drug compared to those who had taken placebo, and a delay in the manifestations of rheumatoid arthritis in those patients who, despite having received the drug abatacept, developed the disease. In particular, the APPIPRA study, which involved more than 200 patients without obvious signs of disease, in addition to demonstrating that abatacept slows down and in some cases blocks the progression of the disease, made it clear that “joint ultrasound allows us to identify patients at greater risk of developing rheumatoid arthritis, because the finding of ultrasound synovitis, or the presence of inflammatory signs on MRI, makes them classified as ‘active’ patients, i.e. with full-blown arthritis, but clinically not visible”, explains D’Agostino.
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The results
In the first study, at the end of the first year, 9% of patients treated with abatacept and 29% of patients in the control group had developed rheumatoid arthritis. At 24 months, only 25% of participants treated with abatacept for one year developed rheumatoid arthritis, versus 37% of the control group. In the second study – AARIA – ‘very early’ therapy with abatacept demonstrated a reduction in inflammation in 57% of treated patients, compared to 31% in the placebo group; in particular, early treatment with abatacept produced a significant improvement in patients’ pain, morning stiffness and quality of life. Only 8% of treated patients versus 35% of the control group developed rheumatoid arthritis. A difference compared to placebo which is maintained even one year after treatment is stopped. “These results demonstrate that treating high-risk subjects at an early stage with a biological drug such as abatacept not only does not create toxicity problems, but seems to slow down the evolution towards clinically evident rheumatoid arthritis,” concludes D’Agostino.