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Individualizing Treatment for Patients With RA, axSpA, and PsA: Considerations and Strategies
Individualizing Treatment for Patients With RA, axSpA, and PsA: Considerations and Strategies

Released: September 14, 2022

Expiration: September 13, 2023

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Key Takeaways:

  • Methotrexate remains the backbone therapy for moderate to severe rheumatoid arthritis but biologic and targeted synthetic disease-modifying antirheumatic drugs (DMARDs) should be added quickly in patients not at target
  • Early diagnosis and treatment in axial spondyloarthritis and psoriatic arthritis decreases disease-related activity and damage, improves symptoms and patient functional status, and may result in delayed disease progression
  • Individualize therapy for axial spondyloarthritis and psoriatic arthritis by considering impacted disease domains and comorbid conditions

This commentary summarizes key takeaways presented during the 2022 Rheumatology APP Bootcamp: Clinical Advances to Enhance Patient Care on managing therapy of patients with rheumatoid arthritis (RA), axial spondyloarthritis (axSpA), and psoriatic arthritis (PsA).

Rheumatoid Arthritis: Key Updates on Methotrexate, Glucocorticoids, and JAK Inhibitor Safety

Methotrexate Recommendations

The 2021 American College of the Rheumatology (ACR) Guideline for the Treatment of Rheumatoid Arthritis recommends methotrexate (MTX) monotherapy in disease-modifying antirheumatic drugs (DMARD)-naive patients with moderate to high disease activity. MTX is preferred due to its established efficacy, safety, and low cost. Patients should be started on a dose of ≥15 mg/week with the consideration that the dose may be split for added tolerability.

For patients not at target despite MTX monotherapy, the ACR guidelines recommend the addition of a biologic DMARD (bDMARD) or targeted synthetic DMARD (tsDMARD) to MTX therapy based on patient-specific comorbidities. If the patient is not at target and already on a bDMARD or tsDMARD, they should be switched to an alternative bDMARD or tsDMARD of a different class as an improvement in disease activity and drug survival has been demonstrated.

Glucocorticoid Recommendations

The 2021 ACR Guidelines recommend using the lowest dose of glucocorticoids (GCs) for the shortest duration possible. Patients who achieve their disease activity target should either be started on a DMARD or switched to a DMARD vs continuing GCs, as their improved disease control should allow for reduced GC use. GCs may still be used to alleviate symptoms prior to the onset of DMARD effect. However, in order to mitigate potential adverse effects of prolonged exposure, GC use should be continually reevaluated to limit total exposure.

JAK Inhibitors for Moderate to Severe RA

In February 2021, the US Food and Drug Administration required warnings about the increased risk of major adverse cardiovascular events (MACE) and malignancy with Janus kinase (JAK) inhibitors indicated for treatment of RA (ie, tofacitinib, baricitinib, and upadacitinib). This warning was issued after reviewing the ORAL Surveillance trial safety data, which showed an increase in MACE and cancers in patients aged ≥50 years with 1 or more cardiovascular risk factors on tofacitinib compared with patients on a tumor necrosis factor inhibitor (TNFi). Several studies have demonstrated clinical benefits of adding a JAK inhibitor to MTX background therapy. Despite these trial results, the 3 JAK inhibitors used for RA share a common mechanism of action and therefore the FDA recommends that JAK inhibitors only be used in patients with an inadequate response or intolerance to 1 or more TNFi. Current and former smokers are at an increased risk for both cardiovascular events and malignancies, and JAK inhibitors should be discontinued in patients that have experienced a myocardial infarction or stroke.

Axial Spondyloarthritis: Treatment Options and Disease Progression

Domains in Therapy Selection

Axial spondyloarthritis, PsA, psoriasis, inflammatory bowel disease, and noninfectious uveitis comprise a unique group of immune-mediated diseases with shared immunopathology. Patients often have clinical features of 1 or more of these diseases or what is referred to as multi-domain disease. The domains of axSpA (ie, spondylitis, psoriasis, enthesitis, enterocolitis, dactylitis, uveitis, and peripheral synovitis) that are relevant to the patient should be considered when choosing treatment options. To help guide individualized therapy, Brüner and colleagues developed the term spondylitis-psoriasis-enthesitis-enterocolitis-dactylitis-uveitis-peripheral synovitis or SPEED-UP spectrum disease and categorized any currently FDA- or European Medicines Agency-approved biologic or targeted synthetic therapy options by their respective indication(s) by domain.

Impact of Therapy on Disease Progression

In a systematic review, Baraliakos and colleagues analyzed the results of 20 studies evaluating the effects of biologic therapies in axSpA on spinal radiographic progression. Using the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS), investigators found minimal and slow spinal progression in patients receiving long-term TNFi therapy. Patients receiving a continuous IL-17A inhibitor (secukinumab) also showed less spinal progression and were stable over 4 years. The key takeaway is that the use of biologic therapy for management of axSpA may delay progression of spinal damage. Additional research is needed to confirm these beneficial outcomes.

Updates in the Management of Psoriatic Arthritis

Delayed Diagnosis of PsA

In a study evaluating 283 patients with PsA, Haroon and colleagues found that the average time from symptom onset to assessment by rheumatology healthcare professionals was 1 year. A diagnostic delay of more than 2 years was associated with low BMI and low education status. Long-term follow up showed that a delay in specialist evaluation of more than 6 months resulted in more disease-related erosions, osteolysis, sacroiliitis, arthritis mutilans, deformed joints, therapy failure, and worse disability. Therefore, early assessment and diagnosis of PsA is key for avoiding worsened long-term psoriatic disease outcomes, negative impacts on comorbidities and complications, and therapeutic failures.

Individualizing Treatment Plans

Like patients with axSpA, most patients with PsA also present with multi-domain disease activity. When planning treatment of PsA with pharmacologic systemic treatments, the current European League Against Rheumatism (EULAR) guidelines recommend considering the disease activity in domains associated with active PsA (ie, polyarthritis [>4 joints] with or without dactylitis, mono- or oligoarthritis, enthesitis, and axial disease).

Additionally, the 2021 treatment recommendations from the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) support a therapeutic approach guided by disease activity within 6 PsA domains including peripheral arthritis, axial disease, enthesitis, dactylitis, skin and nail psoriasis plus the PsA-related comorbidities, uveitis, and inflammatory bowel disease.

Your Thoughts

What are your thoughts and questions on managing patients with rheumatoid arthritis, axial spondyloarthritis, or psoriatic arthritis? Please join the conversation by posting a comment in the discussion section below.