From the Guidelines
For a 70-year-old female with seronegative RA with wrist synovitis, positive TB gold test, ILD, and inadequate response to leflunomide and methylprednisolone, I recommend initiating tocilizumab as the most appropriate biologic. The standard dosing would be 162 mg subcutaneously weekly. Before starting tocilizumab, the patient should receive isoniazid prophylaxis (300 mg daily with vitamin B6 25 mg daily) for latent TB for at least one month. Tocilizumab is preferred in this case because it has shown efficacy in patients with RA-ILD progression despite first ILD treatment, as stated in the 2023 American College of Rheumatology (ACR)/American College of Chest Physicians (CHEST) guideline for the treatment of interstitial lung disease in people with systemic autoimmune rheumatic diseases 1. Additionally, tocilizumab has a lower risk of exacerbating interstitial lung disease compared to other biologics. Regular monitoring of liver function, complete blood count, and pulmonary symptoms is essential. The elevated CRP (15) indicates active inflammation that requires more aggressive therapy than her current regimen provides.
Some key points to consider when initiating tocilizumab include:
- Latent TB screening before initiation
- Monitoring for infusion reactions
- Regular monitoring of liver function, complete blood count, and pulmonary symptoms
- Dose adjustment based on patient response and tolerability
It's also important to note that the patient's ILD and positive TB gold test require careful consideration when selecting a biologic therapy. Tocilizumab has been conditionally recommended for patients with RA-ILD progression despite first ILD treatment, making it a suitable option for this patient 1.
Overall, tocilizumab is a suitable biologic option for this patient, given its efficacy in RA-ILD and relatively favorable safety profile. However, close monitoring and regular follow-up are necessary to ensure optimal patient outcomes.
From the FDA Drug Label
Rituximab is a monoclonal antibody that targets the CD20 antigen expressed on the surface of pre-B and mature B-lymphocytes. Upon binding to CD20, rituximab mediates B-cell lysis. Possible mechanisms of cell lysis include complement dependent cytotoxicity (CDC) and antibody dependent cell mediated cytotoxicity (ADCC) B cells are believed to play a role in the pathogenesis of rheumatoid arthritis (RA) and associated chronic synovitis. In RA patients, treatment with RITUXAN induced depletion of peripheral B lymphocytes, with the majority of patients demonstrating near complete depletion (CD19 counts below the lower limit of quantification, 20 cells/µl) within 2 weeks after receiving the first dose of RITUXAN.
The most appropriate biologic for a 70-year-old female with seronegative RA, synovitis to wrists, positive TB gold but no evidence of active TB, and ILD is Rituximab.
- Key points:
- Rituximab targets CD20 antigen on B-lymphocytes, mediating B-cell lysis.
- B cells play a role in the pathogenesis of RA and associated chronic synovitis.
- Treatment with Rituximab induces depletion of peripheral B lymphocytes in RA patients. 2
From the Research
Treatment Options for Seronegative RA with ILD
The patient in question has seronegative RA with synovitis to wrists, a positive TB gold test but no evidence of active TB, and ILD. The CRP is elevated at 15, and the RA is not responding to Medrol and Leflunomide. Considering the presence of ILD, the choice of biologic therapy is crucial.
Biologic Therapy Options
- Abatacept: Studies have shown that Abatacept may be an effective and safe treatment for patients with RA-ILD 3, 4. It has been observed to improve or stabilize ILD imaging and pulmonary function tests in a significant proportion of patients.
- Tocilizumab: Tocilizumab has also been found to have a good safety profile in patients with RA-ILD and may help stabilize lung involvement 5.
- TNF inhibitors: However, TNF inhibitors have been associated with a potential risk of ILD progression, particularly in patients with pre-existing ILD 6.
Considerations for Treatment Choice
- The patient's ILD status and the potential risks associated with TNF inhibitors should be taken into account when selecting a biologic therapy.
- Abatacept or Tocilizumab may be considered as alternative options, given their relatively safer profiles in patients with ILD.
- The patient's seronegative status and lack of response to Medrol and Leflunomide should also be considered when making treatment decisions, as seronegative RA may have different clinical features and treatment responses compared to seropositive RA 7.