Combination therapy of apremilast and biologics in patients with psoriasis showing biologic fatigue

Abstract

Biologics have been shown to constitute a highly effective treatment for patients with psoriasis. However, a significant number of patients treated with biologics will discontinue them due to loss of efficacy over time, a phenomenon known as biologic fatigue or secondary failure. Combination therapy of biologics with other agents can be considered as a treatment option in such cases. Information regarding the efficacy and safety of adding apremilast to biologic therapy in patients with psoriasis is limited. In the present study, we retrospectively evaluated the efficacy and safety of apremilast combined with biologics in 14 patients with psoriasis showing biologic fatigue at a single hospital. Before the addition of apremilast, the mean Psoriasis Area and Severity Index (PASI) score was 3.2 ± 0.4. At week 24 following the addition of apremilast, the mean PASI score decreased to 1.6 ± 0.3, and four (29%) and seven (50%) patients had achieved 75% and 50% reduction in PASI score, respectively. During the 24 weeks of treatment, diarrhea was observed in four patients, and diarrhea and nausea were observed in one patient. Weight loss of more than 5% bodyweight was observed in two patients. None of the patients discontinued therapy because of these side‐effects. These results suggest that the combination therapy of apremilast and biologics could be a safe, effective option for the management of patients with psoriasis showing biologic fatigue.

Apremilast as an Off-Label Therapeutic Agent

“…methotrexate) obtained PASI50-100 throughout a follow up period of 3-9 months with similar treatment-emergent adverse effects [TEAE] to monotherapy (Table1). 13,[19][20][21][22][23][24][25][26][27][28][29][30][31] Collectively several case studies have noted that the addition of apremilast to either systemic biologic or nonbiologic therapies had a mean additional improvement in PASI scores between 31.8-77.4% for patients that were either unsatisfied with their current regimen or experienced secondary failure. 13,19,21,22 While additional efficacy varied depending on the pre-apremilast regimen, most patients saw durable results with a range of means between 12 and 31 weeks.…”

“…13,[19][20][21][22][23][24][25][26][27][28][29][30][31] Collectively several case studies have noted that the addition of apremilast to either systemic biologic or nonbiologic therapies had a mean additional improvement in PASI scores between 31.8-77.4% for patients that were either unsatisfied with their current regimen or experienced secondary failure. 13,19,21,22 While additional efficacy varied depending on the pre-apremilast regimen, most patients saw durable results with a range of means between 12 and 31 weeks. 13,[19][20][21][22][23][24][25] Several studies also found additional benefit in combining narrow-band UVB (nbUVB) phototherapy with apremilast, with additional improvements in PASI of 76.4-81.5%.…”

“…13,19,21,22 While additional efficacy varied depending on the pre-apremilast regimen, most patients saw durable results with a range of means between 12 and 31 weeks. 13,[19][20][21][22][23][24][25] Several studies also found additional benefit in combining narrow-band UVB (nbUVB) phototherapy with apremilast, with additional improvements in PASI of 76.4-81.5%. 13,25 Furthermore, none of these therapeutic combination resulted in severe infections in the management of psoriasis or psoriatic arthritis.…”

“…Depression or depressive symptoms were not noted in patients on any combination therapy with apremilast. [18][19][20][21][22][23][24][25] Several studies compared apremilast monotherapy to combination therapy with apremilast and found no significant difference in the rate of treatmentemergent adverse effects (TEAE). 22,23 Several case reports also found utility of apremilast in combination therapies, especially in more recalcitrant cases of psoriasis, which had failed multiple topical and systemic agents.…”

“…Many of the studies demonstrated apremilast's efficacy especially for psoriasis for which FDA-approved first (and second line) therapies may have lost efficacy [18][19][20][21][22][23][24][25][26][27][28][29][30][31] or for other moderate to severe dermatoses that were not suitably managed long-term by corticosteroids, or other non-biologic systemic agents . In several cases, apremilast had the same relatively rapid onset of activity (~2-4 weeks) as seen in psoriasis, despite the various diverging types of inflammatory conditions treated.…”