What are the alternatives to Rinvoq (upadacitinib) for the treatment of Rheumatoid Arthritis (RA)?

From the Guidelines

Rinvoq (upadacitinib) can be replaced with other JAK inhibitors like Xeljanz (tofacitinib) or Olumiant (baricitinib) for the treatment of Rheumatoid Arthritis (RA), as recommended by the European League Against Rheumatism (EULAR) in their 2019 update 1. When considering alternatives to Rinvoq, it's essential to evaluate the patient's disease severity, comorbidities, and prior treatment response.

• Traditional disease-modifying antirheumatic drugs (DMARDs) such as methotrexate (starting at 7.5-15mg weekly), leflunomide (20mg daily), sulfasalazine (2-3g daily), and hydroxychloroquine (200-400mg daily) are often first-line treatments.
• Biologic DMARDs offer additional options, including TNF inhibitors (Humira/adalimumab, Enbrel/etanercept, Remicade/infliximab), IL-6 inhibitors (Actemra/tocilizumab, Kevzara/sarilumab), T-cell costimulation modulators (Orencia/abatacept), and B-cell depleting therapies (Rituxan/rituximab). According to the EULAR recommendations, initially, methotrexate plus glucocorticoids and upon insufficient response to this therapy within 3 to 6 months, stratification according to risk factors is recommended 1. With poor prognostic factors (presence of autoantibodies, high disease activity, early erosions or failure of two csDMARDs), any bDMARD or JAK inhibitor should be added to the csDMARD. If this fails, any other bDMARD (from another or the same class) or tsDMARD is recommended 1. Treatment choice ultimately depends on factors like disease severity, comorbidities, prior treatment response, administration preferences (oral vs. injectable), and insurance coverage. Most biologics require regular injections or infusions and immunosuppression monitoring, while conventional DMARDs like methotrexate require regular blood work to monitor liver function and blood counts. Your rheumatologist can help determine which alternative might work best based on your specific situation and disease characteristics.

From the FDA Drug Label

Leflunomide is indicated in adults for the treatment of active rheumatoid arthritis (RA): to reduce signs and symptoms to inhibit structural damage as evidenced by X-ray erosions and joint space narrowing to improve physical function ORENCIA is a prescription medicine that reduces signs and symptoms in: • adults with moderate to severe rheumatoid arthritis (RA), including those who have not been helped enough by other medicines for RA

The alternatives to Rinvoq (upadacitinib) for the treatment of Rheumatoid Arthritis (RA) are:

• Leflunomide 2
• Abatacept (ORENCIA) 3 and 3 These alternatives may be used alone or in combination with other RA treatments.

From the Research

Alternatives to Rinvoq (Upadacitinib) for Rheumatoid Arthritis (RA) Treatment

• Tofacitinib: a JAK inhibitor that has been approved as a second-line treatment for RA, with efficacy and safety profiles comparable to upadacitinib 4, 5, 6, 7
• Baricitinib: another JAK inhibitor that has been approved for RA treatment, with similar efficacy and safety profiles to upadacitinib 4, 5, 6, 7
• Filgotinib: a JAK inhibitor that has been shown to be effective in RA patients with inadequate responses to biologic disease-modifying antirheumatic drugs (bDMARDs) 6
• Adalimumab: a biologic disease-modifying antirheumatic drug (bDMARD) that has been compared to upadacitinib in clinical trials, with upadacitinib showing superior efficacy in some measures 4, 5, 8
• Abatacept: a bDMARD that is being compared to upadacitinib in ongoing clinical trials, with results pending 4

Efficacy Comparison of Alternatives

• Upadacitinib 15 mg and 30 mg daily have been shown to be among the most effective treatments for active RA, with high probabilities of being the best treatment in terms of American College of Rheumatology 20 response rate (SUCRA = 0.820 and 0.762, respectively) 5
• Tofacitinib 10 mg and 5 mg daily have also been shown to be effective, with SUCRA values of 0.623 and 0.424, respectively 5
• Baricitinib 4 mg daily has been shown to have a high probability of achieving the American College of Rheumatology 50 response rate, with a SUCRA value of 0.762 6
• Filgotinib 200 mg daily has been shown to be effective in RA patients with inadequate responses to bDMARDs, with a high probability of achieving the American College of Rheumatology 20 response rate 6

Safety Comparison of Alternatives

• Upadacitinib has been shown to have a similar safety profile to tofacitinib and baricitinib, with no significant differences in serious adverse events 5, 8
• Tofacitinib 5 mg daily has been shown to have a significantly lower serious adverse event rate than upadacitinib 15 mg daily 6
• Baricitinib 4 mg daily has been shown to have a similar safety profile to upadacitinib 15 mg daily, with no significant differences in serious adverse events 6
• Filgotinib 200 mg daily has been shown to have a similar safety profile to upadacitinib 15 mg daily, with no significant differences in serious adverse events 6