Psoriatic arthritis (PsA) is a chronic and invalidating disease characterized by joint and entheseal inflammation affecting 0.05–0.25% of the general population and 6–41% of patients with psoriasis (Gottlieb and Dann, 2009; Laws et al., 2010; Olivieri et al., 2014; Ogdie and Weiss, 2015).

Up until two decades ago, treatment of PsA was often unsatisfactory. Findings based on the immunopathogenesis of the disease have led to the development of biological drugs directed against specific (pathogenetic) targets, in particular tumor necrosis factor-α (TNFα). TNFα is a pleiotropic cytokine which regulates several inflammatory reactions and immune functions through the control of cellular processes and plays a central role in the pathogenesis of PsA (Mantravadi et al., 2017). Anti-TNFα drugs have opened new therapeutic horizons in PsA, proving to be effective in the control of the signs/symptoms of inflammation, in improving the quality of life and the functional outcome, in inhibiting the progression of the structural damage in the peripheral joints and presenting a good safety profile (D'Angelo et al., 2012; Perrotta and Lubrano, 2016; D'Angelo et al., 2017). Treatment strategies of active, predominantly peripheral PsA recommended by International and National Guidelines suggest to use conventional disease-modifying drugs anti-rheumatic (DMARDs), such as methotrexate (MTX). In cases of inadequate response, contraindication or intolerance to at least one DMARD, treatment with biological drugs such as TNFα (adalimumab, infliximab, etanercept, golimumab, or certolizumab pegol) or anti-interleukin therapies (ustekinumab or secukinumab) should be considered (Gossec et al., 2016; Marchesoni et al., 2017).

Adalimumab has been shown to be effective and reasonably safe in reducing disease activity and controlling joint damage in patients with PsA, even in comorbid conditions (D'Angelo et al., 2012). However, despite its generally high efficacy, some patients with PsA may be refractory to adalimumab therapy, may lose response or develop drug intolerance over time (Perrotta and Lubrano, 2016; D'Angelo et al., 2017). The persistence in therapy in real-life clinical practice is increasingly recognised as a surrogate marker for the efficacy and safety of a drug (Saad et al., 2011). National registries provide clinical data from the real-world setting, with the aim to monitor long-term safety of a specific treatment, but they also yield other important information (difficult to achieve in clinical trials), such as drug survival and long-term effectiveness (Armuzzi et al., 2014).

The present real-life study evaluated the persistence of adalimumab in the management of PsA patients over a period of 2 years. Potential baseline clinical and laboratory parameters influencing persistence rate were also evaluated.

Efficacy and safety data currently available for anti-TNFα drugs for the treatment of PsA are mainly derived from randomised clinical trials (RCTs). Although RCTs still represent the most powerful research tool to confirm the efficacy of a treatment, results emerging from these studies are based on a selected population, with the exclusion of co-morbidities, treated and observed for a limited period of time. In routine clinical practice (real life), the decision to choose a specific biologic needs to take into consideration that patients may often be affected by multiple comorbidities, receive concomitant medication, and necessitate treatment for a greater duration, characteristics that are profoundly different from a RCT. It is increasingly recognised that the persistence in treatment is a good surrogate of both effectiveness (efficacy in the real-life setting) and tolerability of a drug (Saad et al., 2011).

The short- and long-term benefit of adalimumab for the treatment of PsA is already documented from several clinical trials and meta-analyses (Gladman et al., 2007; Mease et al., 2009; Burmester et al., 2013). However, little evidence is available on the persistence and effectiveness of adalimumab administered as first- or second-line biologic treatment in the real-life setting.

The results from this real-life study indicate that adalimumab can be considered as a therapeutic option for the long-term treatment in PsA patients, regardless of their prior exposure to biologics or DMARDs or the presence of comorbid diseases. The majority of patients (86.6%) retained treatment with adalimumab for up to 1 year with only a slight reduction observed at 2 years (73.8% persistence), corroborating with findings from European registry studies (70–88%) for 1 year persistence rates (Heiberg et al., 2008; Saad et al., 2009; Glintborg et al., 2011; Aaltonen et al., 2017; Stober et al., 2018). However, our results showed higher rates than another real-life registry performed in Italy, with 2-year retention rate of 48% in PsA patients treated with golimumab (Manara et al., 2017). Furthermore, in that study, no difference was observed in retention rate between first- and second-line treatment in patients with rheumatoid arthritis or PsA (Manara et al., 2017). Although clinical characteristics and disease severity of patients treated in our study were similar to European registries, it is important to note that 68.6% were naïve to biologics and 55.2% were receiving concomitant DMARDs (43.2% in combination with MTX). These features may favour drug response and persistence, since evidence suggests that response to adalimumab is lower after previous TNF inhibitor (Merola et al., 2017) and concomitant MTX can improve anti-TNF drug survival (Glintborg et al., 2011), although other studies dispute the benefit of combined use of DMARDs and anti-TNF agents on drug survival (Mease et al., 2015; Aaltonen et al., 2017). In addition, we did not observe any advantage in drug persistence in patients treated with adalimumab as monotherapy compared to those receiving MTX and/or other DMARDs. Recently, a retrospective single-centre cohort study based in the UK was performed in patients with PsA who initiated anti-TNF therapy (adalimumab in 42% of cases) (Stober et al., 2018). Retention rates were similar to those observed in our study at 12 (79%) and 24 months (73%). Interestingly, the presence of metabolic syndrome and female sex were identified as predictors of lower drug persistence (Stober et al., 2018), findings that have been reported by other groups (Heiberg et al., 2008; Glintborg et al., 2011), but have not been confirmed by our study. The small number of patients with metabolic syndrome and BMI value ≥30 in our cohort might account for the lack of association between obesity and worse adalimumab performance. Why female sex emerged as a predictor of better adalimumab survival rate does not seem to have a logical explanation, although this has also been observed in psoriasis patients (Verma et al., 2018). However, published data on this topic are based on study populations of PsA patients taking any TNF inhibitors and do not investigate drugs individually. Differences in patient characteristics across studies such as age, baseline disease severity and the presence of underlying fibromyalgia may also play a role in gender related differences in drug persistence. Further studies well help to clarify this result in more detail.

High levels of CRP at baseline also predicted improved adalimumab persistence at 24 months in our hands, a finding that has also been observed previously in ankylosing spondylitis (Glintborg et al., 2010) as well as PsA patients (Glintborg et al., 2011; Aaltonen et al., 2017). High CRP levels at baseline are associated with systemic inflammation and, therefore, may help identify patients with more active disease who are more likely to benefit from adalimumab treatment than patients with less inflammatory active disease.

Given the lack of association observed in our analysis between a range of laboratory and clinical variables with persistence rate, adalimumab may be considered as a viable therapeutic option in a heterogeneous population of patients in the real-world PsA setting, without the need to restrict treatment to specific subgroups or special patient populations.

High persistence rate was paralleled with a marked improvement in arthritis measures such as TJC, SJC, DAPSA, enthesitis, and dactylitis. PASI and CRP were also significantly improved as early as 12 months and remained stable up to 2 years. We also observed a good safety profile with adalimumab in PsA patients. Of 26.5% PsA patients who discontinued treatment with adalimumab after 2 years, only 6.1% were actually due to adverse events.

While the main strength of the present study lies in the large sample size (N = 424) and 2-year follow-up period, subgroup analysis for some specific clinical (e.g. tender and swollen joint count, PASI and DAPSA) and laboratory measures (e.g. CRP) were hampered by missing data for some patients. The retrospective design was another limitation. However, as this study involved 16 rheumatological centres, evaluating the real-life use of adalimumab as first or second-line treatment in biologic naïve or previous biologic failure in the PsA setting, results can be generalised to the larger Italian territory.

In this large real-life cohort, the use of adalimumab was found to be highly effective in PsA patients. High retention was achieved at 1 (86.6%) and 2 years (73.8%) and given the lack of association between several laboratory and clinical variables with persistence rate, adalimumab may be considered as a viable therapeutic option in a heterogeneous population of patients in the real-world PsA setting.

The datasets generated for this study are available upon request from the corresponding author.

Ethics committee approval from all participating centres and written informed consent for the anonymous use of personal data were obtained from every patient, in compliance with the Italian Legislative Decree 196/2003. The patients/participants provided their written informed consent to participate in this study.

SD'A conceived and designed the study. All authors were responsible for data collection/acquisition and have critically reviewed and approved the final version of the manuscript prior to submission.

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.