What should be added to Saphnelo (anifrolumab) and hydroxychloroquine for a systemic lupus erythematosus (SLE) patient with persistent joint pain, joint swelling, elevated erythrocyte sedimentation rate (ESR), and low complement level (C3)?

From the Guidelines

For a patient with systemic lupus erythematosus (SLE) who is already on Saphnelo (anifrolumab) and hydroxychloroquine but still experiencing persistent joint pain, joint swelling, elevated ESR, and low C3 complement level, I recommend adding methotrexate at a starting dose of 7.5-10 mg once weekly, with gradual titration up to 20-25 mg weekly as tolerated. Methotrexate should be accompanied by folic acid supplementation (1 mg daily or 5 mg weekly, taken 24-48 hours after methotrexate) to reduce side effects. This recommendation is based on the 2019 update of the EULAR recommendations for the management of SLE, which suggests the use of immunomodulating agents such as methotrexate, azathioprine, or mycophenolate in patients not responding to hydroxychloroquine (alone or in combination with glucocorticoids) or patients unable to reduce glucocorticoids below doses acceptable for chronic use 1. The persistent symptoms and abnormal laboratory values indicate ongoing disease activity despite current therapy, justifying this escalation. Methotrexate works by inhibiting dihydrofolate reductase and promoting adenosine release, which reduces inflammation in joint tissues. Regular monitoring of complete blood count, liver function, and renal function every 4-8 weeks initially, then every 3 months once stable, is essential. If methotrexate is contraindicated or poorly tolerated, alternatives include leflunomide (20 mg daily) or a short course of low-dose oral prednisone (5-10 mg daily) with a tapering plan while waiting for methotrexate to take effect. A more recent study in 2024 also supports the use of methotrexate in SLE patients, highlighting its efficacy in reducing disease activity and improving quality of life 1. Additionally, monitoring of cardiovascular risk factors, osteoporosis, and infection risk is crucial in SLE patients, as recommended by the European League Against Rheumatism 1.

Some key points to consider:

• Methotrexate is a well-established treatment for SLE, with a long history of use and a favorable safety profile.
• Folic acid supplementation is essential to reduce the risk of methotrexate-related side effects.
• Regular monitoring of laboratory parameters is crucial to ensure safe use of methotrexate.
• Alternative treatments, such as leflunomide or prednisone, may be considered if methotrexate is not tolerated or contraindicated.
• The treatment plan should be individualized based on the patient's specific needs and disease activity.

Overall, the addition of methotrexate to the patient's current treatment regimen is a reasonable and evidence-based approach to managing persistent joint pain and swelling in SLE.

From the FDA Drug Label

2.4 Dosage for Systemic Lupus Erythematosus in Adults The recommended dosage is 200 mg given once daily, or 400 mg given once daily or in two divided doses.

The patient is already on hydroxychloroquine and Saphnelo (anifrolumab). To address the persistent joint pain, joint swelling, elevated ESR, and low complement level (C3) in this SLE patient, consider adding a corticosteroid as the drug label for hydroxychloroquine mentions that corticosteroids, salicylates, and other antirheumatic agents may be used concomitantly with hydroxychloroquine sulfate tablets 2.

From the Research

Treatment Options for Systemic Lupus Erythematosus (SLE)

The patient is currently on Saphnelo (anifrolumab) and hydroxychloroquine, with persistent joint pain, joint swelling, elevated erythrocyte sedimentation rate (ESR), and low complement level (C3). Considering the treatment goals for SLE, which include reducing disease exacerbations, hospitalizations, and organ damage due to the disease or treatment toxicity 3, the following options can be considered:

• Immunosuppressive agents: Azathioprine, mycophenolate mofetil, and cyclophosphamide are commonly used to treat moderate to severe SLE 3.
• Biologic therapies: In addition to anifrolumab, other biologic therapies such as belimumab and voclosporin have been approved for the treatment of SLE 3, 4.
• Glucocorticoids: While not a long-term solution, glucocorticoids can be used to manage acute flares and reduce inflammation 4.

Joint Involvement in SLE

Joint involvement is a common manifestation of SLE, and the swollen to tender joint count ratio (STR) can be used to assess disease activity 5. The patient's elevated ESR and low C3 level suggest active disease, and the presence of joint pain and swelling indicates the need for effective management of joint symptoms.

Patient-Reported Outcomes

Patient-reported outcomes, such as the LupusPRO and Work Productivity and Activity Impairment: Lupus (WPAI-Lupus), can provide valuable insights into the impact of SLE on daily life 6. Reducing pain and improving quality of life are important treatment goals for patients with SLE.

Efficacy and Safety of Anifrolumab

Anifrolumab has been shown to be effective in reducing disease activity and improving outcomes in patients with active SLE 7. However, it is associated with an increased risk of herpes zoster infection, and patients should be monitored closely for this adverse event.

Next Steps

Based on the available evidence, the following options can be considered for the patient:

• Adding an immunosuppressive agent, such as azathioprine or mycophenolate mofetil, to the current treatment regimen 3.
• Continuing to monitor the patient's response to anifrolumab and adjusting the treatment plan as needed 7.
• Considering the addition of a biologic therapy, such as belimumab, if the patient's disease activity remains high despite current treatment 3, 4.