Will autoimmune markers remain positive in patients with rheumatoid arthritis (RA) who are undergoing treatment?

From the Guidelines

Yes, autoimmune markers can still come back positive in rheumatoid arthritis (RA) patients who are receiving treatment. Common markers like rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibodies (anti-CCP) often remain detectable even when symptoms improve with medication. This persistence occurs because these treatments typically control inflammation and disease activity rather than completely eliminating the underlying autoimmune process. Some medications, particularly biologics like rituximab (which depletes B cells), may reduce antibody levels in some patients, but this effect varies considerably between individuals. Disease-modifying antirheumatic drugs (DMARDs) such as methotrexate, hydroxychloroquine, and TNF inhibitors can effectively control symptoms while autoantibodies remain present. This is why physicians typically monitor disease activity through clinical symptoms, inflammatory markers (ESR, CRP), and joint examinations rather than solely relying on autoantibody levels to assess treatment effectiveness. Patients should understand that persistent positive autoimmune markers don't necessarily indicate treatment failure if their symptoms and inflammation are well-controlled, as stated in the 2021 American College of Rheumatology guideline for the treatment of rheumatoid arthritis 1.

Key points to consider:

• The goal of treatment is to control symptoms and disease activity, not necessarily to eliminate autoimmune markers.
• Autoantibody levels can remain positive despite effective treatment.
• Treatment decisions should be based on a shared decision-making process and reevaluated regularly.
• Disease activity levels should be monitored using validated instruments, and treatment modified to minimize disease activity.
• The 2021 American College of Rheumatology guideline provides recommendations for the treatment of rheumatoid arthritis, including the use of DMARDs and biologics 1.

In terms of specific treatments, the guideline recommends:

• Using conventional DMARDs (csDMARDs) such as methotrexate, hydroxychloroquine, and sulfasalazine as first-line treatment.
• Adding biologics such as TNF inhibitors or interleukin-6 receptor inhibitors for patients who do not respond to csDMARDs.
• Considering targeted synthetic DMARDs (tsDMARDs) such as JAK inhibitors for patients who do not respond to biologics.
• Tapering or discontinuing treatment for patients who have achieved low disease activity or remission for at least 6 months, as stated in the guideline 1.

Overall, the management of rheumatoid arthritis requires a comprehensive approach that takes into account the patient's individual needs and circumstances, and involves regular monitoring and adjustment of treatment to achieve optimal outcomes.

From the FDA Drug Label

In RA Studies I and II, the percentage of patients evaluated for antinuclear antibodies (ANA) who developed new positive ANA (titer ≥ 1:40) was higher in patients treated with Enbrel (11%) than in placebo-treated patients (5%) The percentage of patients who developed new positive anti-double-stranded DNA antibodies was also higher by radioimmunoassay (15% of patients treated with Enbrel compared to 4% of placebo-treated patients) and by Crithidia luciliae assay (3% of patients treated with Enbrel compared to none of placebo-treated patients) The proportion of patients treated with Enbrel who developed anticardiolipin antibodies was similarly increased compared to placebo-treated patients.

Autoimmune markers may still come back positive in patients with rheumatoid arthritis being treated with etanercept.

• Antinuclear antibodies (ANA): 11% of patients treated with Enbrel developed new positive ANA, compared to 5% of placebo-treated patients.
• Anti-double-stranded DNA antibodies: 15% of patients treated with Enbrel developed new positive antibodies, compared to 4% of placebo-treated patients.
• Anticardiolipin antibodies: the proportion of patients treated with Enbrel who developed these antibodies was increased compared to placebo-treated patients 2.

From the Research

Autoimmune Markers in Rheumatoid Arthritis Treatment

• The provided studies do not directly address whether autoimmune markers will come back positive if rheumatoid arthritis is being treated 3, 4, 5, 6, 7.
• However, it is known that rheumatoid arthritis is a chronic, inflammatory, systemic autoimmune disease, and treatment goals are to reduce pain and stop or slow further damage 4.
• Treatment with disease-modifying antirheumatic drugs (DMARDs) such as methotrexate, sulfasalazine, and hydroxychloroquine can be effective in reducing disease activity and achieving remission or low disease activity 3, 6, 7.
• The treatment target is remission or a state of at least low disease activity, which should be attained within 6 months, and a treat-to-target strategy can prevent RA-related disability 7.
• It is not clear from the provided studies how treatment affects autoimmune markers, and further research would be needed to determine this.

Treatment Outcomes and Autoimmune Markers

• Studies have shown that early diagnosis and treatment of RA can avert or substantially slow progression of joint damage in up to 90% of patients 7.
• Methotrexate is first-line therapy and should be prescribed at an optimal dose of 25 mg weekly and in combination with glucocorticoids; 40% to 50% of patients reach remission or at least low disease activity with this regimen 7.
• If this treatment fails, sequential application of targeted therapies, such as biologic agents or Janus kinase inhibitors in combination with methotrexate, have allowed up to 75% of these patients to reach the treatment target over time 7.
• However, the effect of these treatments on autoimmune markers is not explicitly stated in the provided studies 3, 4, 5, 6, 7.