A total of 15 dermatologists were invited, and all agreed, to participate in the Working Group. Dermatologist backgrounds were similar for participants in the preliminary meeting and the second and final consensus meetings. All dermatologists worked at university hospitals, scientific research institutes, or were healthcare professionals in Italy and had clinical expertise in the management of patients with PsO treated with biologicals, including secukinumab.

Consensus was reached for all statements. The voting results for each statement are provided in Tables 1, 2 and 3. In the following sections, the consensus statements from each of the three topics are discussed, along with any supporting evidence from the literature.

Table 1 Statements A1 to A12 from the final round of the Delphi process—regarding characteristics of secukinumab and criteria for patient selection to achieve long-term benefitsTable 2 Statements B1 to B6 from the final round of the Delphi process—regarding strategies to maintain secukinumab effectiveness in the long termTable 3 Statements C1 to C3 from the final round of the Delphi process—regarding strategies for patient support to promote treatment adherenceCharacteristics of Secukinumab and Criteria for Patient Selection to Achieve Long-Term Benefits

A total of 12 statements were developed describing secukinumab characteristics regarding criteria for selection of the most appropriate patients for secukinumab treatment to ensure long-term treatment success. Consensus was reached on all 12 statements (Table 1).

A.1. Secukinumab achieves a rapid response. Although other anti-IL-17 agents share this characteristic, the strength of secukinumab resides in the vast clinical-practice experience gathered over the years.

Anti-IL-17A agents are rapidly acting, with a faster onset of action than anti-IL-23 agents, and can achieve a rapid response in patients with PsO [17, 18]. Secukinumab is the first approved, recombinant high-affinity, fully human monoclonal antibody of the immunoglobulin (Ig) G1/kappa isotype that selectively targets IL-17A; thus, secukinumab can be differentiated from other, more recently approved biological agents because of its extensive clinical experience [19, 20]. The long-term safety of secukinumab, demonstrated by an almost decade-long experience, is a particular strength of the agent [10,11,12,13,14, 21].

When PsO is associated with marked inflammation, perhaps in patients treated exclusively with conventional disease-modifying antirheumatic drugs (cDMARDs), such as cyclosporine, patients may subsequently present with moderate-to-severe disease. Here, secukinumab would be an appropriate choice, as it acts to reduce inflammation via an effect on high-sensitivity C-reactive protein and neutrophil–lymphocyte ratio in patients with a high inflammatory burden [22].

A.2. Biological-naïve patients with moderate PsO are the optimal candidates for secukinumab, even though other drugs introduced after secukinumab may sometimes demonstrate better performance.

Patients with moderate PsO who are biological-naïve and with a relatively short disease history are optimal candidates for secukinumab [23,24,25,26]. However, a clear and consistent definition of moderate PsO, and a potentially more precise indicator of disease severity than Psoriasis Area and Severity Index (PASI) score, remain to be determined. Nevertheless, moderate PsO, as currently broadly defined, is prevalent in the experience of the Working Group dermatologists, who report that patients with moderate PsO are increasingly seeking dermatological consultation. Importantly, patients who receive early treatment and who are biological-naïve are deemed the most appropriate for treatment with any biological (including secukinumab) and are likely to persist on therapy [23]. This is supported by the SUPREME 2.0 study, in which secukinumab treatment survival was significantly greater at 42 months in patients naïve to biologicals than in biological-experienced patients, at 75% versus 62% (Fig. 1) [27].

Fig. 1

Reproduced from Russo F, et al. Clin Cosmet Investig Dermatol 2023;16:3561–74 [27] (https://doi.org/10.2147/CCID.S416149) originally published by and used with permission from Dove Medical Press Ltd

Proportions of biological-naïve and biological-experienced patients still on treatment with secukinumab after 42 months.

Treatment should be initiated as early as possible, as shown in the STEPIn study, in which early secukinumab intervention in patients with new-onset moderate-to-severe plaque PsO was superior to narrow band ultraviolet B (nb-UVB) phototherapy: the primary endpoint of a PASI90 response at week 52 was attained by 91% of patients in the secukinumab arm compared with 42% in the nb-UVB arm (P < 0.0001) [24].

When biosimilar TNF inhibitors are no longer effective, a rapidly acting agent that can preserve or positively impact patient quality of life and satisfaction with therapy is needed [28,29,30].

A.3. Patients with PsO involving sensitive sites are optimal candidates for secukinumab.

Transition from PsO to PsA substantially increases disease burden [31], and early evidence suggests that treatment with an agent such as secukinumab, which blocks inflammatory IL-17A, may help prevent such transition in patients with PsO who are at increased risk of PsA [32, 33]. An increasing body of evidence suggests that PsO at sites such as the nails may predict the subsequent development of PsA [34, 35]. Notably, the placebo-controlled TRANSFIGURE study demonstrated strong and clinically meaningful efficacy for secukinumab for up to 2.5 years in patients with moderate-to-severe nail PsO [36].

Recently, the European Alliance of Associations for Rheumatology (formerly the European League Against Rheumatism; EULAR) published a consensus document highlighting points to consider in the transition from PsO to PsA, proposing the following classification [37]:

●:

Patients at high risk of PsA: Patients with some characteristics (e.g. obesity, nail PsO or arthralgia).

●:

Patients with subclinical PsA: Patients with ultrasound or magnetic resonance imaging evidence of inflammatory enthesopathy/joint inflammation.

●:

Patients with clinical PsA: Patients with clinically manifested PsA.

Patients at high risk of PsA or with subclinical PsA can be considered candidates for secukinumab, as supported by data from clinical trials [32, 33].

Other sensitive sites include the elbows, palmoplantar areas and genital region, all of which have been deemed difficult-to-treat and are thus critical areas regarding response to therapy and impact on patient quality of life [38, 39]. Secukinumab has shown real-world effectiveness in the treatment of palmoplantar PsO and scalp PsO [28, 40, 41].

Ideally, a new assessment index, possibly merging the PASI, Dermatology Life Quality Index (DLQI) and Body Surface Area (BSA) indexes, could provide a numerical disease grading that would be useful for determining patients for whom secukinumab treatment would be most appropriate.

A.4. In cases where biosimilar anti-TNF treatment has proven ineffective (so-called crypto-naïve), secukinumab is an advisable option.

Currently, anti-TNF agents used in clinical practice are primarily biosimilars. Some patients must switch to a different agent because an anti-TNF biological agent, often a biosimilar, has lost effectiveness over time, regardless of exposure duration. These patients are not biological-naïve and can be viewed as a new phenotype, which should be characterised in terms of response to treatment. In addition, these patients, for whom the advisory board coined the term crypto-naïve, are those who, according to healthcare regulations, were necessarily exposed to a biosimilar as first-line biological therapy for less than 12 months and whose treatment interruption could be due to any reason. The term crypto-naïve is not intended to apply to cases of primary ineffectiveness of anti-TNF biologicals. The board considered that secukinumab can be a useful option for crypto-naïve patients, although PASI is not expected to be high in these patients. This option would also be helpful in terms of management costs.

A.5. Patients at high risk of developing PsA are optimal candidates for treatment with secukinumab, including patients with PsO localised at predictive sites (such as nails, scalp, sacral region) who are not currently symptomatic.

Patients at high risk of PsA [37] are patients with PsO who have not yet been diagnosed with PsA; these patients should be managed exclusively by dermatologists. Although evidence is lacking for the role of anti-TNF agents in the treatment of patients with PsO with the involvement of difficult-to-treat areas, the reimbursement rules in some regions of Italy (e.g. Lazio) mandate using anti-TNF agents even in this setting, and clinicians prescribing different agents may be requested to justify their choice.

A.6. Lean or normal-weight patients are optimal candidates for secukinumab, with an increased likelihood of positive and long-lasting responses.

While weight control is crucial for PsO management [42], patients with PsO frequently also have obesity, which can reduce the effectiveness of systemic treatments, including biologicals [42]. Although patients with PsO and a normal or low body mass index (BMI) are a minority [43, 44], they should still be considered, as they may respond rapidly and well to secukinumab [45, 46].

A high BMI is associated with reduced persistence of a PASI ≤ 3 response in patients treated with secukinumab, with multivariate analysis in one 85-patient study associating high BMI with a decreased chance of achieving PASI ≤ 3 at week 78 [47]. Moreover, one board member reported that in his clinical-practice experience, the few adverse events reported with secukinumab occurred in patients with obesity.

A.7. The administration frequency of secukinumab (every 2 weeks) offers dosing flexibility, especially beneficial for individuals with increased weight, although this flexibility increases management costs for the healthcare system.

Currently, secukinumab can be administered every 14 or 28 days. This ability to reduce the dosing interval provides flexibility, allowing administration of an adequate dose in patients with obesity (BMI > 30 kg/m2). The secukinumab summary of product characteristics (SmPC) states that “Based on clinical response, a maintenance dose of 300 mg every 2 weeks may provide additional benefit for patients with a body weight of 90 kg or higher” [9]. Some participants reported administering a 150-mg dose in between two 300-mg monthly doses of secukinumab in patients with a poor response. While participants said that this was done regardless of patient body weight, most patients encountered in real-world clinical practice are overweight or obese. One participant’s experience was that patients with obesity, who were initially unresponsive to secukinumab 150 mg, started responding after weight loss. Administering secukinumab 300 mg every 2 weeks in patients with high body weight, as allowed for in the secukinumab SmPC [9], is preferable to switching to another agent, which would require an induction period [48].

A.8. Secukinumab is an optimal choice for patients with PsO associated with active disease who are receiving cDMARDs or cyclosporine.

This statement is intended to allow consideration of secukinumab in the treatment of more severe disease, by including biological-naïve patients who experience flares after or while on cDMARDs, including cyclosporine. Specifically, poor tolerability of cyclosporine—even in patients in clinical remission—could drive a switch to an anti-IL-17A agent [49, 50]. In patients with a long history of PsO and who are confident with prolonged cyclosporine use, cyclosporine dosage tapering may be difficult, since patients tend to self-regulate according to their clinical conditions. Of note, one participant reported the case of a 19-year-old woman with obesity who responded well to full-dose cyclosporine, but who experienced a relapse when the dose was reduced. The patient was switched to an anti-IL-23 agent, a choice driven by the patient’s fear of injections and consistent with treatment tailoring; however, the patient is responding poorly. In this case, a switch from cyclosporine to an anti-IL-17A agent such as secukinumab would have been the optimal choice.

In summary, secukinumab is an optimal choice for any patient receiving a cDMARD, including cyclosporine, and who presents with a relapse, regardless of the effectiveness of the cDMARD.

A.9. As the first-in-class anti-IL-17 agent, secukinumab is favoured due to its extensive clinical-practice experience. Secukinumab is a well-established choice, particularly in patients with comorbidities.

Comorbidities, which affect approximately 73% of patients with PsO [51], are often a deciding factor in the choice of treatment drug class [3,4,5,6,7]. Within any drug class, dermatologists can then choose the optimal agent for an individual patient. In patients with atopy or a history of atopy, secukinumab may not be the preferred first choice because of rare reports of paradoxical eczema in patients receiving anti-IL-17A agents [52].

Some dermatologists may feel more confident prescribing anti-IL-23 agents rather than other biologicals [53]. This may be because anti-IL-23 agents are perceived as safer as a result of their indication in several immune-mediated inflammatory diseases [54]. However, a substantial body of literature demonstrates secukinumab safety in frail patients or patients with comorbidities, including cardiovascular and oncological diseases [55,56,57,58]. Unfortunately, so far, guidelines have not acknowledged this evidence, which has important implications for clinical practice.

Importantly, real-world data suggest that secukinumab may have a generally favourable safety profile in patients with inactive hepatitis B virus (HBV), hepatitis C virus or latent tuberculosis infection [59,60,61,62,63], without promoting a significant risk for viral reactivation in treated patients receiving antiviral prophylaxis [64,65,66,67]. Furthermore, secukinumab is as safe as IL-23 inhibitors in patients with latent tuberculosis who are not receiving specific prophylaxis during treatment [68]. Nonetheless, the secukinumab SmPC points out that HBV or tuberculosis reactivation can occur in patients treated with secukinumab [9]. Relevant clinical and laboratory monitoring are required for patients with evidence of positive HBV serology or latent tuberculosis, and secukinumab should not be given to patients with active tuberculosis [9].

A.10. Oncology patients, even those with severe PsO, could benefit from the use of secukinumab, considering that anti-IL-17 agents have proven safe in the oncological setting. The preference for using secukinumab is supported by extensive clinical-practice experience.

Guidelines recommend caution when prescribing biologicals in patients with PsO and a history of cancer, particularly in patients with diagnosis and treatment within the past 5 years, and in patients with an increased baseline cancer risk [69]. However, in clinical practice, dermatologists do not always consider guideline recommendations for this patient population. Moreover, the choice of PsO treatment also depends on oncologists, who should be consulted before starting biologicals in patients with a recent history, or increased risk, of cancer. The Working Group noted that some oncologists are unwilling to use anti-IL-17A agents and may even believe that these agents entail a risk to patients. This is despite a lack of definitive evidence for either anti-IL-17A or anti-IL-23 agents and increased cancer risk, with much of the available evidence pointing to a decreased risk for both classes [70, 71]. Furthermore, some data demonstrate that anti-IL-17A agents act on vascular endothelial growth factor and inhibit tumorigenesis [72].

At the Clinical Dermatology Centre in Torino, Italy, flare-ups of latent PsO have been observed in patients receiving immunotherapy for melanoma. Dermatologists treat these flare-ups with either anti-IL-23 or anti-IL-17A agents. The most likely reason for choosing anti-IL-23 over anti-IL-17A agents is convenience of the oral formulation, especially in patients already receiving intravenous immunotherapy, and is unlikely to be due to any safety concerns.

Finally, recent literature suggests that when secukinumab is administered to patients with recent history or current malignancies, it is not associated with a significant risk of oncological recurrence or progression [73,74,75].

A.11. Patients with cardiovascular disease are optimal candidates for secukinumab, as literature reports indicate secukinumab safety with no observed impact on cardiovascular risk. Similar to the oncology setting, the preference for using secukinumab is supported by extensive clinical-practice experience.

Considerable evidence demonstrates the safety of secukinumab in patients with cardiovascular disease [22, 56, 76,77,78,79]. In addition, in a prospective observational study in patients with moderate-to-severe PsO and low cardiovascular risk, anti-IL-17A agents reduced non-calcified plaque burden by 12% at 1 year, which was significantly greater than the reductions achieved with anti-IL-23 agents (2%) or anti-TNF treatments (5%); a reduction in necrotic core was also evident [80]. Moreover, in a 52-week trial in patients with moderate-to-severe PsO without clinical cardiovascular disease, endothelial function was significantly better (higher flow-mediated dilation) than baseline in patients receiving secukinumab, suggesting that secukinumab may have a beneficial impact on cardiovascular risk in patients with PsO via improved endothelial function [