Combination therapy of apremilast and secukinumab in patients with moderate‐to‐severe, recalcitrant plaque psoriasis

Over recent decades, much progress has been made towards psoriasis management.1 2 Along with traditional systemic therapies (methotrexate, ciclosporin A, acitretin), the introduction of monoclonal antibodies such as anti‐tumour necrosis factor drugs has allowed achievement of 75% reduction in Psoriasis Area and Severity Index (PASI75).1 2 Innovative targets are constantly being investigated. The approval in 2015 of secukinumab, a monoclonal antibody against interleukin (IL)‐17, set up a new frontier regarding the management of moderate to severe psoriasis owing to its prompt PASI response and the considerable number of patients achieving PASI90 and PASI100.3 Until recently, all biological therapies (BTs) required invasive administration (intravenous or subcutaneous).1 Apremilast, the first targeted therapy with oral administration, changed this status.4 This small molecule is a phosphodiesterase‐4 inhibitor, which regulates systemic immune homeostasis through cyclic adenosine monophosphate.4 Owing to its severity, recalcitrant psoriasis requires combinations of different therapies.1 However, to date, there are no validated protocols for such treatment.1 Recently, some authors have proposed the combination of apremilast with other BTs.4 5 Nevertheless, there are only a few reported cases of combination therapy (CT) of secukinumab and apremilast.4 5 We report our experience with this combination in psoriasis. Four adult outpatients with longstanding psoriasis (duration of 10–20 years) who had failed to maintain PASI75 despite appropriate therapies were selected. At enrolment into the study, they had already undergone treatment with phototherapy, methotrexate (MTX), ciclosporin A, acitretin and all the available BTs (infliximab, adalimumab, etanercept and ustekinumab). In particular, two patients were on adalimumab, and one each on ustekinumab and etanercept. Mean PASI was 19.5. Given that an add‐on therapy with MTX had not yielded any relevant improvement in psoriasis, we discontinued the existing therapy for all four patients and initiated treatment with secukinumab (Table 1). Within the first 3 months, PASI90 was achieved, during a minimum of 12 months (Patient 4) to a maximum of 21 months (Patient 3). At relapse, mean PASI was 8. Overview of patients of the case series: anamnestic and clinical data. CT, combination therapy (with secukinumab and apremilast); PASI, Psoriasis Area and Severity Index; PsA, psoriatic arthritis; SMT, secukinumab monotherapy. aBeginning of the study; btime of worsening of psoriasis with SMT (before starting CT with apremilast); cend of the study (while still on CT secukinumab and apremilast). Overview of patients of the case series: anamnestic and clinical data. CT, combination therapy (with secukinumab and apremilast); PASI, Psoriasis Area and Severity Index; PsA, psoriatic arthritis; SMT, secukinumab monotherapy. aBeginning of the study; btime of worsening of psoriasis with SMT (before starting CT with apremilast); cend of the study (while still on CT secukinumab and apremilast). In addition, as the patients refused MTX owing to its mode of administration and previous lack of efficacy on their disease, CT with secukinumab and apremilast was proposed. On this therapy, Patient 3 achieved PASI100, while the other three patients obtained at least PASI75, and mean PASI at the end of the study was 2. Follow‐up lasted between 6 and 9 months. No serious adverse events were noted, other than mild diarrhoea coinciding with the beginning of the treatment with apremilast, and that became self‐limited over time. Up to 30% of patients with recalcitrant psoriasis are placed on CT, typically anti‐TNFα with methotrexate,1 in spite of limited data describing ustekinumab combined with MTX, ciclosporin A or acitretin.1 The use of CT with apremilast is increasing, despite the fact that only a few reports on its use exist.4 5 To our knowledge, the current study is the first case series. The main limit of this study is the small number of patients; nevertheless, we consider it a worthwhile series, as it sheds further light on this novel CT. Despite the added cost of both treatments, this CT proved to be a recommendable choice, based on both the clinician's assessment and the patients' perception of their quality of life, as affirmed by Nisar.5 However, it is reasonable to ask to what extent should patients' perceptions guide clinicians' therapeutic choices; only time will tell. Conflict of interest: the authors declare that they have no conflicts of interest.