Secukinumab treatment in psoriatic patients: Italian experiences

Psoriasis is an inflammatory condition involving several organs, and not only a chronic skin disease as previously considered (1). A high level of discomfort is usually present, and the disease may have a huge negative impact on social and working life. Skin psoriasis may be a challenging disease for the dermatologist because of either localization of lesions or of clinically serious variants. One such example is acrodermatitis continua of Hallopeau, an uncommon variant of pustular psoriasis, which is characterized by a relapsing, sterile, pustular eruption of hands and feet (2). Moreover, erythrodermic psoriasis (EP) is a severe variant of psoriasis characterized by prominent erythema of the whole body surface (3). In addition to the cutaneous manifestations, psoriasis may present with other organ damage: psoriatic arthritis (PsA) is a chronic inflammatory condition that affects up to 30% of psoriatic patients, and ocular comorbidity was reported in 10–15% of patients with plaque psoriasis (1,4). Management of such different clinical presentations may involve several specialists and require topical and systemic therapy. New drugs directed toward new therapeutic targets have recently complemented traditional therapy for psoriasis.

IL-17A plays an important role in the pathogenesis of psoriasis and PsA. Produced by immune cells, it modulates neutrophils, endothelial cells, fibroblast-like synoviocytes, chondrocytes, and osteoblasts behaviors (5,6). The activation of these cells promotes the release of inflammatory cytokines and induces pathological processes in several tissues: vessel activation, matrix destruction, cartilage damage, and bone erosion (5,6). Secukinumab is a human IgG1 monoclonal antibody that selectively binds and neutralizes IL-17A (7,8). Its efficacy in chronic plaque psoriasis has been demonstrated by several clinical trials and secukinumab has recently been approved for the treatment of psoriatic arthritis in adults, alone or in association with methotrexate (MTX) when the response to previous DMARDs is inadequate (7). Articles published in this supplement report clinical experiences in the use of secukinumab in different psoriasis variants. Real life practice has confirmed results obtained in clinical trials. Secukinumab provided an effective and rapid improvement of plaque psoriasis, even in localizations that are known to be difficult to treat. As shown by Malagoli et al., Pistone et al., and in severe patients as the one described by Galluzzo et al. secukinumab as a therapeutic upgrade for patients who respond to anti-TNF-α drug but who have the persistent disease in limited critical areas, resulted effectively. In the Authors’ experience, 12 patients had achieved PASI 75 (mean PASI was 6.1) after 2 years of anti-TNF-α administration. Nevertheless, subjects had residual psoriasis localized in critical areas. Eleven of 12 patients achieved PASI 90/100 at week 3/5 of treatment with secukinumab, retaining the effect for 52 weeks of treatment, with irrelevant residual scalp lesions. Pistone et al. described results obtained with secukinumab in patients eligible for systemic treatment of psoriasis who also had nail involvement, a quite frequent symptom associated with great impairment in quality of life. Management of nail psoriasis is challenging due to inefficient absorption of topical drugs by the nail unit, and low responsiveness to conventional systemic therapies. Limited data on the efficacy of biological agents in this specific localization of psoriasis have been published at present, and consistent and good-quality evidence is lacking for guidelines on the treatment of psoriasis with nail involvement (9,10). After 6 weeks of secukinumab treatment 300 mg, a clinically significant response was observed, with progressive reduction of both skin and nail disease indexes. The average reduction of PASI was 75%, of BSA 70%, and of NAPSI 50%, at week 6. At week 12, NAPSI reduction was by 80%, of PASI 90%, and of BSA 97%. Noteworthy, the regression of skin psoriasis was associated with a relevant, although slightly slower, resolution of nail localization. Monotherapy of psoriasis with several localizations represents a new perspective for psoriasis since previous approaches included different drugs for different localizations. Use of a single drug may improve adherence to treatment, a serious problem for a chronic disease such as psoriasis, and could reduce intolerance by avoiding polytherapy. Furthermore, Pistone et al. stated that secukinumab provided rapid improvement of scalp psoriasis to a group of 10 adult patients with moderate to severe plaque psoriasis located in the scalp, who were eligible for biological therapy. Six patients achieved at least a 70% improvement in the PSSI score, after 6 weeks of treatment, and similar improvement was observed for skin psoriasis. Galluzzo et al. reported a rapid response to secukinumab in a patient affected by erythrodermic psoriasis (EP), after conventional therapies failure. Management of EP is difficult, not standardized, and often ineffective. Traditionally employed systemic therapies for EP include methotrexate, cyclosporine, and oral retinoid, and systemic steroids are used in many cases. Both the efficacy and safety of conventional therapeutic options are unsatisfactory. Studies regarding the use of biological agents in EP were limited to few case series (11). Results suggested that anti-psoriatic biological agents targeting the IL-23/Th17 pathway, including anti-IL23p19 antibodies (tildrakizumab and guselkumab), and anti-IL17 agents (secukinumab, ixekizumab, and brodalumab) might play a positive role in the therapy of EP (12,13). One clinical trial in a cohort of Japanese patients evaluated the efficacy and safety of brodalumab (an anti-IL17-receptor antibody) for the EP treatment (12). Ixekizumab, a new humanized anti-interleukin-17A monoclonal antibody, has recently been evaluated for EP in a phase 3 study (UNCOVER-J), on a little cohort of Japanese subjects (13). Recently, clinical experiences suggesting that secukinumab could become a treatment choice for EP, especially in patients that have had unsuccessful previous therapies even with biologics, have been published (14–17). Balestri et al. reported that add-on therapy with secukinumab in a patient with unsatisfactorily controlled acrodermatitis continua of Hallopeau provided sustained improvement, confirming similar experiences (18,19). The authors had chosen this drug based on previously published reports both in patients with plaque psoriasis and with pustular diseases (20,21), and because of a convenient schedule that favored adherence. They acknowledged that clinical studies are needed to confirm their observation and to identify the appropriate dosage of secukinumab. In addition, significant improvement was obtained in systemic manifestations such as psoriatic arthritis (Nicola et al.) and ocular comorbidity (Bartolotta et al.).

Nicola et al. reported their clinical experience with secukinumab, in a real-life setting, in 13 patients affected by PsA associated with skin psoriasis who did not respond to DMARDS or anti-TNFα therapies. They observed an improvement of psoriasis at 4-week treatment. At 16 weeks, this improvement involved both skin and joints disease, restoration of almost normal inflammation marker levels, and enhanced quality of life. Ocular comorbidity was reported in 10–15% of patients with plaque psoriasis, but such data is likely to be underestimated. Ocular diseases most frequently found in patients with psoriasis are seborrheic blepharitis that may progress toward madarosis, ectropion, entropion, anterior uveitis, and dry eye syndrome (1,22,23). Treatment of this comorbidity has not been defined yet. The patient described by Bartolotta et al. had plaque psoriasis with concomitant dry eye disease. This condition, quite frequent in patients with psoriasis, contributes to life impairment, and it should be carefully treated to obtain patient satisfaction. Evidence of secukinumab activity on eye disease is lacking, nevertheless, this drug could be expected to improve eye inflammation, as it interferes with the recruitment of cells into the eye surface that has a pivotal role in the physiopathology of the dry eye (1). As several forms of psoriasis may coexist in a single patient, the use of a single systemic drug may reduce the risk of adverse events and improve patient adherence. Secukinumab seems to be a promising drug for the management of psoriasis, both when limited to the skin and when involving other organs.

Luca IdolazziOspedale Civile Maggiore, Rheumatology Unit, University of Verona, Verona, Italy[email protected]

Disclosure statement

Dr. Idolazzi received fees from Eli Lilly, Novartis, UCB pharma, Abbvie.