Update on Oral Molecules

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This article discusses the latest evidence on oral molecules for the treatment of psoriasis and psoriatic arthritis.

oral molecule

Oral molecules continue to play a significant role in the treatment of psoriatic disease. With advances in the understanding and treatment of psoriasis and psoriatic arthritis (PsA), more targeted treatment options are available to patients. This has changed the way oral molecules are now prescribed, with pre-21st century molecules also not being used as often. This article discusses the latest evidence on the use of oral molecules, from new research on the safety and efficacy of apremilast (Otezla) to the potential for Janus kinase (JAK) inhibitors for the treatment of psoriasis and PsA.

Current Uses of Apremilast

Apremilast was approved by the FDA in 2014 for the treatment of moderate to severe plaque psoriasis and PsA. More recently, apremilast has been used as monotherapy for patients with more moderate psoriasis and in combination with other systemic treatments for more severe disease.

The UNVEIL study, conducted by Linda Stein Gold, MD, and colleagues,1 supported the use of apremilast as monotherapy among participants with moderate psoriasis. Compared with placebo, more participants receiving apremilast achieved improvements in Physician’s Global Assessment and body surface area after 52 weeks of treatment. In addition, participants who switched from placebo to apremilast at week 16 experienced improvements through week 52. 

The LIBERATE study,2 which was a longer-term study for moderate to severe patients, showed improved and maintained Psoriasis Area and Severity Index (PASI) scores among participants who received apremilast during 104 weeks of treatment. In the study, participants were assigned 1:1:1 to apremilast, placebo, or etanercept (Enbrel) for 16 weeks. After week 16, those assigned to placebo or etanercept were switched to apremilast. The data showed that the majority of participants who received apremilast at baseline or were switched at week 16 achieved PASI 75 and maintained response through 104 weeks. In addition, apremilast was found to improve nail and scalp PASI scores through 104 weeks of treatment. Data from both trials confirms long-term efficacy and safety of apremilast, for moderate and moderate to severe patients, and even for patients with psoriasis in difficult to treat areas. 

In addition, new evidence shows that apremilast can be safely combined with biologics and narrowband UV-B phototherapy. A retrospective open-label study, conducted by Samy Metyas, MD, and colleagues,3 included 22 participants with both severe psoriasis and PsA, and showed that adding apremilast to biologic therapy was safe and helped further improve PASI scores. Biologics included in the study were adalimumab (Humira), ustekinumab (Stelara), infliximab (Remicade), golimumab (Simponi), etanercept, and certolizumab pegol (Cimzia). No major adverse events were observed, such as cancer or serious infection, and minor adverse events were consistent with findings from clinical trials, including nausea, diarrhea, and weight loss.  Additionally, participants remained on both therapies for several months, with mean treatment duration of 8 months (range: 1-24 months). 

Jerry Bagel, MD, and colleagues4 demonstrated improved efficacy and safety of apremilast when combined with narrowband UV-B. Participants received narrowband UV-B 3 times per week and apremilast 30 mg twice daily for 12 weeks. By week 12, 73% of participants achieved PASI 75, with 45% achieving PASI 90. The only adverse event noted during the study period was an increase in first-degree burns. Dr Bagel noted that apremilast in combination with narrowband UV-B may increase the risk of minor burns and patients should especially be monitored for this adverse event. However, apremilast in combination with narrowband UV-B showed greater efficacy compared with previously reported data with apremilast monotherapy. Perhaps to mitigate the risk of burns, patients who receive narrowband UV-B and take apremilast should have less incremental increase in UV doses if they show signs of burning.

A subanalyses from phase 3 trials with apremilast (ESTEEM 1 and 2)5 demonstrated that patients who had longer psoriasis disease duration (>10 years) had a more rapid relapse of their psoriasis after apremilast discontinuation than those who had shorter disease duration (<10 years). Between 70% to 78% of patients with longer disease duration relapsed compared with 22% to 29% of patients with shorter duration of psoriasis. In most patients who relapsed, relapse occurred by 8 weeks after apremilast discontinuation. After reinitiating treatment, most patients did regain their PASI responses. 

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