Can a patient with worsening psoriasis be switched to another Tumor Necrosis Factor (TNF) inhibitor after failing one TNF inhibitor?

From the Guidelines

Yes, a patient with worsening psoriasis can be switched to another Tumor Necrosis Factor (TNF) inhibitor after failing one TNF inhibitor, as recommended by the 2019 American College of Rheumatology/National Psoriasis Foundation guideline 1. When considering switching between TNF inhibitors, options include adalimumab (Humira, 40mg every other week), etanercept (Enbrel, 50mg weekly), infliximab (Remicade, 5mg/kg at weeks 0,2,6, then every 8 weeks), certolizumab pegol (Cimzia, 400mg at weeks 0,2,4, then 200mg every other week), or golimumab (Simponi, 50mg monthly). Before switching, it's essential to confirm that the worsening is truly a paradoxical reaction to the medication rather than inadequate dosing or other factors, as paradoxical worsening occurs in approximately 1-5% of patients on TNF inhibitors, and the mechanism is thought to involve altered cytokine balance, particularly increased interferon-alpha production 1. While some patients who fail one TNF inhibitor may respond to another due to differences in molecular structure and mechanism, others may benefit more from switching to a different class of biologics entirely, such as IL-17 inhibitors (secukinumab, ixekizumab) or IL-23 inhibitors (guselkumab, risankizumab), as suggested by the guideline 1. Key considerations for switching include:

• The patient's primary or secondary failure to the initial TNF inhibitor
• The presence of any serious adverse events or severe psoriasis associated with the initial TNF inhibitor
• The patient's preference for less frequent drug administration or oral therapy
• The presence of concomitant conditions, such as inflammatory bowel disease (IBD) or a history of recurrent Candida infections Close monitoring is essential after switching to detect any similar adverse reactions promptly, and to assess the patient's response to the new therapy 1. It is also important to note that the British Association of Dermatologists' guidelines for biologic interventions for psoriasis 2009 recommend that a second TNF antagonist may be considered for patients who do not respond to a TNF antagonist (either primary or secondary failure) 1. However, the more recent guideline from 2019 provides more specific recommendations for switching between TNF inhibitors and to other biologic agents, and should be prioritized in clinical decision-making 1.

From the FDA Drug Label

Patients who had previously received a TNF blocker were allowed to enroll if they had previously had loss of response or intolerance to that TNF blocker. The answer is: Yes, a patient with worsening psoriasis can be switched to another Tumor Necrosis Factor (TNF) inhibitor after failing one TNF inhibitor, as the label indicates that patients who had previously had loss of response or intolerance to a TNF blocker were allowed to enroll in the study 2.

From the Research

Switching to Another TNF Inhibitor

• A patient with worsening psoriasis who has failed one TNF inhibitor may be considered for switching to another TNF inhibitor 3.
• The decision to switch should be based on individual patient factors, such as treatment resistance, co-morbidities, and patient demographics 4, 5.
• Studies have shown that some patients who discontinued anti-TNF-α therapy due to worsening psoriasis achieved higher rates of complete response compared to those who continued therapy 3.

Considerations for Switching

• The pharmacodynamic profile of anti-TNF-α inhibitors should be fully considered when planning therapy strategies, especially in cases of secondary failures or poor adherence to treatment 5.
• The unique pharmacological profile of each TNF inhibitor, such as infliximab, adalimumab, and etanercept, can have therapeutic implications when choosing a particular TNFi for a patient 6.
• Considerations such as infection and malignancy risk, patient demographics, and co-morbidities may make certain TNF-alpha inhibitors or ustekinumab an excellent choice for therapy in particular patient subgroups 4.

Efficacy and Safety of TNF Inhibitors

• TNF inhibitors have been shown to be efficacious in the treatment of moderate-to-severe plaque psoriasis, with each drug having a unique pharmacological profile 6.
• The efficacy and safety of switching to an alternative anti-TNF-α agent have not been fully explored, and further studies are needed to define the role of anti-TNF alpha agents in the management of psoriasis 3, 7.