What is the next step in treatment for a 60-year-old patient with rheumatoid arthritis who has failed Xeljanz (tofacitinib), Rinvoq (upadacitinib), Orencia (abatacept), Kevzara (sarilumab), and Cimzia (certolizumab pegol)?

From the Guidelines

For a 60-year-old rheumatoid arthritis patient who has failed multiple biologics including JAK inhibitors (Xeljanz, Rinvoq), T-cell co-stimulation modulator (Orencia), IL-6 inhibitor (Kevzara), and TNF inhibitor (Cimzia), the next step would be to try rituximab (Rituxan) or another TNF inhibitor that hasn't been used previously, such as adalimumab (Humira), etanercept (Enbrel), or infliximab (Remicade). This recommendation is based on the most recent guidelines for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs, as outlined in the 2019 update by the European League Against Rheumatism 1.

The patient's history of failing multiple biologics suggests a need to explore alternative mechanisms of action. Rituximab, a B-cell depleting therapy, targets CD20-positive B cells, which play a crucial role in RA pathogenesis, offering a different approach than the previously failed treatments. Before initiating rituximab, screening for hepatitis B is essential due to the risk of reactivation.

Alternatively, switching to a different TNF inhibitor may be effective, as cross-resistance within this class is not universal. The 2019 EULAR recommendations support the use of another bDMARD or a tsDMARD if one has failed, and specifically mention that if one TNF inhibitor therapy has failed, patients may receive an agent with another mode of action or a second TNF inhibitor 1.

If these options fail, consideration of combination therapy with conventional DMARDs (such as methotrexate, hydroxychloroquine, sulfasalazine) or referral to a specialized rheumatology center for clinical trial participation may be warranted. The importance of continuing pain management and physical/occupational therapy throughout this process cannot be overstated, as it remains crucial for symptom control and maintaining function.

Key considerations in the management of this patient include:

• The need for frequent monitoring (every 1–3 months) and adjustment of therapy if there is no improvement by at most 3 months after the start of treatment or the target has not been reached by 6 months 1.
• The potential for tapering bDMARDs or tsDMARDs if the patient is in persistent remission after having tapered glucocorticoids, especially if this treatment is combined with a csDMARD 1.
• The importance of shared decision-making between the patient and the rheumatologist, considering the risks and benefits of respective therapies and the patient's personal preferences 1.

Given the complexity of rheumatoid arthritis management and the individual variability in response to different therapies, a personalized approach, guided by the most recent evidence and expert recommendations, is essential to optimize outcomes for this patient.

From the FDA Drug Label

The efficacy and safety of intravenously administered tocilizumab was assessed in five randomized, double-blind, multicenter studies in patients greater than 18 years with active rheumatoid arthritis diagnosed according to American College of Rheumatology (ACR) criteria. Study V (NCT00106522) evaluated patients with moderate to severe active rheumatoid arthritis who had an inadequate clinical response or were intolerant to one or more TNF antagonist therapies.

The next step in treatment regimen and therapy for the patient who has failed Xeljanz (tofacitinib), Rinvoq (upadacitinib), Orencia (abatacept), Kevzara (sarilumab), and Cimzia (certolizumab) could be tocilizumab, as it has been studied in patients with an inadequate response to TNF antagonists 2.

• Tocilizumab is an option for patients who have failed other biologics.
• The patient's treatment history and current condition should be taken into account when deciding on the next step in treatment.
• It is essential to consider the patient's overall health and potential interactions with other medications when initiating tocilizumab therapy.

From the Research

Treatment Options for Rheumatoid Arthritis

The patient has failed multiple biologic treatments, including Xeljanz (tofacitinib), Rinvoq (upadacitinib), Orencia (abatacept), Kevzara (sarilumab), and Cimzia (certolizumab). Considering the patient's history, the next step in treatment regimen and therapy could be:

• Exploring other JAK inhibitors, as the patient has already been treated with tofacitinib and upadacitinib, which target the JAK/STAT pathway 3, 4
• Considering alternative biologic therapies that target different pathways, such as interleukin-6 (IL-6) inhibitors or T-cell costimulation modulators
• Evaluating the patient's response to previous treatments and identifying potential patterns or biomarkers that could inform future treatment decisions

Biologic Therapies for Rheumatoid Arthritis

Biologic therapies have revolutionized the treatment of rheumatoid arthritis, offering new options for patients who have failed conventional therapies. Some key points to consider when selecting a biologic therapy include:

• The patient's medical history and comorbidities
• The mechanism of action of the biologic therapy and its potential benefits and risks
• The patient's preferences and values, including dosing frequency and route of administration
• The availability of clinical trial data and real-world evidence to support the use of the biologic therapy in patients with rheumatoid arthritis 5, 6

Treatment Failure and Discontinuation

Treatment failure and discontinuation are common challenges in the management of rheumatoid arthritis. Factors that contribute to treatment failure include:

• Loss of efficacy
• Adverse events
• Patient non-adherence
• Inadequate dosing or duration of treatment
• Presence of comorbidities or concomitant medications that interact with the biologic therapy 7