Understanding Apremilast in Psoriasis Treatment
Apremilast, marketed as Otezla®, is an oral phosphodiesterase-4 (PDE4) inhibitor used to treat moderate-to-severe plaque psoriasis and psoriatic arthritis. Unlike more complex biologic therapies, it works intracellularly by increasing cyclic adenosine monophosphate (cAMP) levels, which helps reduce the production of inflammatory mediators. This makes it a compelling oral option for patients who may not be candidates for more aggressive treatments.
The Importance of Real-World Data
Clinical trials are the gold standard for drug approval, but they often exclude older adults due to complex health profiles, polypharmacy, and comorbidities. This creates a gap in our understanding of how treatments perform in real-world clinical practice, where patients are older, sicker, and on more medications. Real-world studies fill this gap by observing how apremilast performs in typical, daily-practice settings with a more representative patient population.
Evaluating Effectiveness in Older Adults
Real-world studies have provided important insights into apremilast's efficacy in older patients (typically defined as age 65 or older). A multicenter French and Italian study of 135 patients (mean age 73.5) found that 45.2% achieved a Physician's Global Assessment (PGA) score of 0 or 1 (clear or almost clear) within 3 to 6 months. This level of effectiveness is encouraging and aligns with results seen in younger populations. Another study in Italy noted that patients on apremilast for 6 months reported significant improvements in their quality of life, alongside clinically relevant improvements in symptoms. The continuation rate, however, varied. In the French/Italian study, one-year continuation rates were better for those between 65-84 compared to the very elderly (aged 85+).
Safety and Adverse Events in Clinical Practice
The safety profile of apremilast in older patients is a key consideration, especially given age-related physiological changes and concurrent health issues. Real-world data largely mirrors the adverse event (AE) profile seen in clinical trials, with the most common side effects being gastrointestinal (diarrhea, nausea).
Common Adverse Events:
- Diarrhea
- Nausea
- Headache
- Upper respiratory tract infections
- Abdominal pain
However, real-world studies show some critical differences when stratifying by age. The French/Italian study found that while AEs were the main cause of discontinuation for many, they were significantly more frequent in patients aged 75 and over. This increased frequency of adverse events in the older subgroups led to higher discontinuation rates. The FDA also notes that older patients may be at a higher risk of complications from severe gastrointestinal side effects.
Serious Adverse Events (SAEs):
In the same French/Italian study, serious adverse events were reported in 12.6% of patients, a higher rate than seen in phase III trials. The frequency of SAEs also increased with age, necessitating a higher level of vigilance from healthcare providers for the very elderly.
Comparative Overview: Clinical Trials vs. Real-World Evidence
| Feature | Clinical Trials | Real-World Evidence (Older Patients) |
|---|---|---|
| Patient Profile | Often younger, healthier, fewer comorbidities. | Includes patients with more comorbidities, polypharmacy, and varying disease severity. |
| Adverse Events | Similar common AEs (GI, headache) reported. | Similar common AEs, but with a higher frequency, especially in patients over 75. |
| Discontinuation | Lack of efficacy or withdrawal often cited. | AEs are the main reason for discontinuation, especially in the oldest subgroups. |
| Effectiveness | Higher reported efficacy rates (e.g., higher PASI75/PASI90). | Possibly lower overall efficacy rates, but significant quality of life improvement noted. |
Practical Considerations for Geriatric Psoriasis Management
For healthcare providers and patients considering apremilast, several factors are particularly relevant for the older population:
- Increased Vigilance for AEs: Providers should be aware of the increased risk of AEs, particularly gastrointestinal, in the very elderly and monitor these patients more closely.
- Assessment of Comorbidities: Given the higher prevalence of conditions like hypertension and kidney disease, a thorough assessment is crucial. Dose adjustment may be necessary for patients with severe renal impairment.
- Polypharmacy Management: The risk of drug interactions with concurrent medications, including over-the-counter and herbal supplements, must be considered.
- Individualized Goals: Treatment decisions for older adults should prioritize what is most distressing to the patient, whether it is joint pain, itching, or skin appearance. Apremilast can be a good option when minimizing immunosuppression is a priority.
- Patient Education: Ensuring patients are aware of potential side effects and the importance of reporting them can improve adherence and safety.
Conclusion
Real-world studies confirm that apremilast is an effective and safe oral treatment for older patients with psoriasis, offering a valuable alternative to other systemic therapies. However, the data highlights key nuances: adverse events are more frequent in the very elderly (over 75), leading to higher discontinuation rates, and serious adverse events may be more common than in controlled trials. For older patients, a tailored approach involving increased monitoring and careful consideration of comorbidities is essential to maximize the benefits and minimize the risks of apremilast therapy. For further information, consult reliable medical resources like the American Academy of Dermatology at https://www.aad.org/.
