From the Guidelines
Failure of phosphodiesterase type 4 inhibitors (PDE4i) in patients with psoriatic arthritis (PsA) is often due to inadequate response, and alternative therapies such as biologic disease-modifying antirheumatic drugs (bDMARDs) or Janus kinase inhibitors (JAKi) should be considered. The most recent and highest quality study, published in 2024 1, recommends that PDE4 inhibitors may be considered in patients with mild disease and an inadequate response to at least one conventional synthetic disease-modifying antirheumatic drug (csDMARD), in whom neither a bDMARD nor a JAKi is appropriate.
Causes of PDE4i Failure
- Inadequate dosing
- Poor medication adherence due to gastrointestinal side effects
- Inappropriate patient selection
Alternative Therapies
- bDMARDs, such as tumor necrosis factor inhibitors (TNFi) or interleukin-17 inhibitors (IL-17i)
- JAKi
- csDMARDs, such as methotrexate or sulfasalazine
Management of PDE4i Failure
- Ensure proper adherence to the standard PDE4i dose
- Consider adding or switching to alternative therapies
- Gradual dose titration may improve tolerability
- Taking the medication with food and using anti-emetics can help manage gastrointestinal side effects
According to the 2022 updated treatment recommendations for PsA 1, PDE4i may be considered for patients with peripheral arthritis and an inadequate response to at least one csDMARD, in whom neither a bDMARD nor a JAKi is appropriate. However, the use of PDE4i is generally reserved for patients with mild disease, and alternative therapies should be considered in patients with more severe disease or inadequate response to PDE4i. Additionally, the 2020 EULAR recommendations for the management of PsA with pharmacological therapies 1 also support the use of PDE4i in patients with mild disease and an inadequate response to at least one csDMARD. The 2022 GRAPPA updated treatment recommendations for PsA 1 also provide evidence-based guidelines for the use of PDE4i in patients with PsA.
From the FDA Drug Label
The FDA drug label does not answer the question.
From the Research
Failure of PDE4i
- The failure of phosphodiesterase 4 inhibitors (PDE4i) in treating psoriasis is not directly addressed in the provided studies, as they primarily focus on the efficacy and safety of apremilast, a selective PDE4 inhibitor, in treating moderate to severe plaque psoriasis 2, 3, 4, 5, 6.
- However, the studies suggest that apremilast is effective in reducing the severity of psoriasis by inhibiting the production of pro-inflammatory cytokines and increasing anti-inflammatory mediators 2, 4, 6.
- The mechanism of action of PDE4 inhibitors, including apremilast, involves increasing intracellular cyclic adenosine monophosphate (cAMP) levels, which leads to a reduction in inflammatory mediators and an increase in anti-inflammatory mediators 4, 6.
- The provided studies do not report on the failure of PDE4i, but rather on the efficacy and safety of apremilast in treating psoriasis, suggesting that PDE4 inhibitors may be a viable treatment option for this condition 2, 3, 4, 5, 6.
Potential Reasons for Failure
- The failure of PDE4i in individual patients may be due to various factors, such as differences in disease severity, individual response to treatment, or concomitant use of other medications 3, 5.
- However, the provided studies do not specifically address the potential reasons for failure of PDE4i, and further research would be needed to investigate this topic.
Clinical Implications
- The efficacy and safety of apremilast in treating psoriasis suggest that PDE4 inhibitors may be a useful treatment option for patients with moderate to severe plaque psoriasis 2, 3, 4, 5, 6.
- Clinicians should consider the potential benefits and risks of PDE4 inhibitors, including apremilast, when treating patients with psoriasis, and monitor patients closely for any adverse effects or lack of response to treatment 3, 5.