Treating Rheumatoid Arthritis with Synthetic and Biologic Disease-Modifying Antirheumatic Drugs (DMARDs)

In 2022, the European Alliance of Associations for Rheumatology (EULAR) updated its recommendations for the treatment of rheumatoid arthritis (RA), placing strong emphasis on safety, efficacy, and the rational use of conventional synthetic (csDMARDs), biologic (bDMARDs), and targeted synthetic DMARDs (tsDMARDs, including JAK inhibitors). These updated guidelines integrate the latest scientific evidence and clinical experience to support optimal care for patients living with RA. They are the result of a consensus among a global panel of leading rheumatologists and patient representatives.

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Core Principles

Effective management of rheumatoid arthritis requires a comprehensive and precise treatment approach—one that places equal importance on medical expertise and the informed preferences of the patient. The latest EULAR guidelines highlight shared decision-making between the patient and the rheumatologist as a fundamental principle. This collaborative process is vital, as it considers not only clinical data and evidence-based standards, but also each patient’s lifestyle, personal values, and individual goals. As such, it received the highest possible level of agreement among the experts involved (LoA 10/10).

Treatment choices in RA should be primarily guided by disease activity—meaning the intensity of inflammation and the patient’s clinical symptoms. Medication safety is also a major consideration, especially in the presence of comorbidities such as cardiovascular disease, diabetes, chronic infections, or a history of malignancy. Monitoring structural damage over time is equally important, particularly when joint deformities or reduced function of the hands and feet begin to emerge. All these factors must be discussed collaboratively to determine the most appropriate course of action at any given point.

Rheumatologists are the specialists best equipped to lead RA care. Their expertise in modern treatment options, potential complications, and complex therapeutic strategies is crucial to managing this condition. While access to rheumatology specialists may be limited in some regions, the ideal scenario is for them to play a central role in treatment decisions and long-term care planning.

RA is a chronic, evolving disease. Over time, patients may need to adjust their treatment plans. A drug that was once effective might lose its efficacy, or new side effects may arise. Moreover, ongoing medical research continuously brings new medications with novel mechanisms and improved safety profiles to the market. This means RA patients should have access to a variety of treatment options and be prepared for changes or combination therapies to achieve optimal outcomes.

Lastly, modern RA care also considers social and economic dimensions. The disease can lead to work disability, diminished quality of life, and increased healthcare costs. Responsible care involves striking a balance between drug efficacy and affordability. If two treatments are shown to be equally effective and safe for a given patient, the more cost-effective option should be prioritized. This not only promotes broader access to care but also eases the financial burden on families and healthcare systems.

These principles are not just abstract ideals—they reflect the heart of modern rheumatology, striving for evidence-based, accessible, and personalized care aimed at helping every person with RA live their best possible life.

Personalized Recommendations for Patients

1. Start Treatment Early DMARD therapy should begin as soon as RA is diagnosed. Early intervention helps prevent permanent joint damage.

2. Set a Clear Treatment Goal The goal is to achieve and maintain remission or low disease activity. Remission means no symptoms or inflammation for at least 6 months.

3. Regular Monitoring and Timely Adjustments For active RA, follow-up visits should occur every 1–3 months. If no improvement is seen within 3 months, or treatment goals are not met within 6 months, adjustments should be made.

4. Methotrexate as First-Line Therapy Methotrexate is the preferred initial DMARD unless contraindicated or poorly tolerated. Alternatives include leflunomide or sulfasalazine if methotrexate is not an option.

5. Glucocorticoids – Short-Term Use Only Glucocorticoids may be used at the start of treatment, but for no more than 3 months. They should be tapered off as soon as possible due to risks (e.g., infections, cardiovascular disease, osteoporosis). If long-term steroid use is required, a new DMARD should be considered.

6. When Initial Therapy Isn’t Enough If the patient has no poor prognostic factors: try a different csDMARD. If poor prognostic factors are present (e.g., autoantibodies, high disease activity, early erosions, failure of 2 csDMARDs): add a bDMARD or—when appropriate—a JAK inhibitor, with careful risk evaluation (especially in patients over 65, smokers, or those with cardiovascular disease or a history of cancer).

7. Combination Therapy for Enhanced Effectiveness bDMARDs or tsDMARDs should ideally be combined with a csDMARD. If a csDMARD cannot be used due to intolerance, IL-6 inhibitors or JAK inhibitors are preferred.

8. Switching Biologics or Targeted Therapies If a bDMARD or tsDMARD is ineffective, switch to another with a different mechanism of action.

9. Consider Tapering, But Never Stop on Your Own If the patient remains in stable remission, gradual dose reduction may be considered. However, treatment should never be stopped without medical supervision.

Simple, Practical Tips for Patients

• Be an active participant in decisions about your treatment.

• Keep regular appointments with your rheumatologist—even if you’re feeling well.

• Follow your prescribed treatment plan; do not stop or change medications on your own.

• Report any side effects or changes in symptoms to your doctor.

• Inform your healthcare provider about any other medical conditions or new medications.

• Ask about available biologic and synthetic alternatives, including generic and biosimilar options.

• Know that early, targeted treatment significantly reduces the risk of disability.

Controversial or Uncertain Aspects of RA Treatment

• The long-term safety of JAK inhibitors remains a concern for patients at higher risk for cardiovascular disease or cancer.

• The role of chronic low-dose corticosteroids is still under debate—particularly in older adults and in countries with limited access to biologic therapies.

• Some treatment regimens—such as triple csDMARD combinations—currently lack strong evidence to support routine use.

“Chronic use of glucocorticoids is not recommended and should be discontinued after 3 months, if possible.” — EULAR Task Force

Expert Opinions

Modern rheumatoid arthritis management is guided not only by scientific evidence but also by the strong consensus of leading rheumatology experts. Their perspectives lend authority to today’s treatment recommendations and reinforce the importance of individualized care and continual adaptation of therapy.

Professor Josef Smolen, from the Medical University of Vienna—one of the world’s most cited rheumatologists and lead coordinator of the EULAR Task Force—emphasizes:

“Treatment must be a joint decision between the patient and the rheumatologist, taking into account each patient’s preferences and unique circumstances.”

This statement is particularly meaningful because it underlines that effective treatment is not just about prescribing the right medication. It requires a foundation of trust, open communication, and a genuine partnership between patient and physician. Each step in the treatment journey should reflect not only the medical indications but also the patient’s lifestyle, concerns, values, and personal goals. This collaborative model increases patient engagement and greatly improves the likelihood of long-term success.

Early diagnosis, personalized and targeted treatment, ongoing monitoring, and shared decision-making are all key to controlling rheumatoid arthritis and preventing complications. Thanks to advances in treatment, remission or low disease activity is now achievable for most patients.

The EULAR Task Force also takes a clear position on the long-term use of corticosteroids.

“Chronic use of glucocorticoids is not recommended and should be discontinued after 3 months, if possible.”

This conclusion is grounded in extensive clinical experience and numerous studies showing that, while corticosteroids can provide fast and often dramatic relief during disease flare-ups, long-term use carries significant risks. These include increased infections, osteoporosis, diabetes, high blood pressure, cardiovascular events, and even higher rates of certain cancers. Prolonged reliance on corticosteroids is seen as a red flag—an indication that the current DMARD regimen may be inadequate and should be re-evaluated. Clear communication and education about the risks and benefits of steroids are essential to avoid unsafe self-management.

Professor Robert Landewé, from Amsterdam University Medical Centers and another leading voice in the field, firmly states:

“Early and aggressive treatment with DMARDs reduces the risk of long-term damage and disability in RA.”

This perspective reflects the broader scientific consensus: a slow or hesitant treatment approach often leads to irreversible joint changes and reduced physical function. That’s why, from the moment of diagnosis, an active and decisive treatment plan is essential—one aimed at rapidly suppressing inflammation and achieving remission or low disease activity.

Final Thoughts

Experts agree that modern rheumatology is personalized, dynamic, and centered on meaningful dialogue with the patient. It combines cutting-edge scientific knowledge with deep respect for individual choice and human experience. This balanced, collaborative approach is what leads to the best outcomes for people living with rheumatoid arthritis.

Questions & Answers: Rheumatoid Arthritis Treatment

1. When should I start treatment for rheumatoid arthritis, and why is early treatment important?

Answer: Treatment with disease-modifying antirheumatic drugs (DMARDs) should begin as soon as possible after a diagnosis of rheumatoid arthritis (RA). Early treatment is crucial because it helps prevent permanent joint damage, reduces the risk of long-term disability, and improves the chances of achieving remission (a state with no symptoms or inflammation). Experts agree that the earlier targeted treatment begins, the better the long-term outcome.

2. What are the main types of medications used to treat rheumatoid arthritis?

Answer: RA treatment typically involves three main categories of DMARDs:

• Conventional synthetic DMARDs (csDMARDs): These include methotrexate (the gold standard), leflunomide, and sulfasalazine.

• Biologic DMARDs (bDMARDs): Modern therapies that target specific inflammatory pathways, such as anti-TNF and anti-IL-6 agents.

• Targeted synthetic DMARDs (tsDMARDs): These include JAK inhibitors, which act on intracellular signaling pathways linked to inflammation.

The choice and combination of these medications depend on disease activity, individual risk factors, and how well previous treatments have worked. Methotrexate is usually the first-line treatment unless contraindicated.

3. What are the treatment goals, and how is progress monitored?

Answer: The primary goal is to achieve and maintain remission—or at least low disease activity—for every patient. This means minimizing or eliminating symptoms, preserving joint function, and preventing long-term deformities.

For patients with active RA, follow-up visits should be scheduled every 1–3 months. If there is no improvement within 3 months or if remission or low disease activity is not achieved within 6 months, the treatment plan should be adjusted. This approach ensures timely responses to changes in the patient’s condition.

4. What are the risks and limitations of corticosteroids and JAK inhibitors?

Answer: Corticosteroids (glucocorticoids) can be helpful for quickly reducing inflammation at the beginning of treatment or during flares. However, their use should be limited to no more than 3 months. Long-term use is associated with serious risks such as infections, osteoporosis, high blood pressure, diabetes, cardiovascular disease, and more. Continued reliance on corticosteroids often signals that the current DMARD therapy needs to be re-evaluated.

JAK inhibitors are effective for many patients but should be used with caution in individuals at higher risk for cardiovascular events or cancer. Their long-term safety is still being studied, especially in these high-risk groups.

5. What is the patient’s role in treatment decisions, and why does it matter?

Answer: Today’s treatment approach places the patient at the center of the decision-making process. All treatment choices should be made collaboratively between the rheumatologist and the patient. This means factoring in personal preferences, lifestyle, concerns, values, and individual goals—alongside clinical guidelines.

This collaborative model helps build trust, improves adherence to the treatment plan, and increases the likelihood of long-term success. It’s also essential for patients to attend regular check-ups, report any new symptoms or side effects, and never stop or change their medications without medical guidance.

Source: EULAR Recommendations for the Management of Rheumatoid Arthritis with Synthetic and Biological Disease-Modifying Antirheumatic Drugs: 2022 Update doi: 10.1136/ard-2022-223356corr1