Analysis of the prevalence of ankylosing spondylitis and treatment patterns and drug utilization among affected patients: an Italian real-world study.

OBJECTIVES: To evaluate the prevalence of ankylosing spondylitis (AS) and associated treatment patterns and drug utilization in real-world clinical practice in Italy. METHODS: This observational study used data from administrative databases of selected Italian entities and included patients with AS diagnosis identified by ICD-9-CM and/or exemption codes. Patients without biologic disease-modifying antirheumatic drug (bDMARD) prescriptions prior to inclusion were defined bio-naïve. A cross-sectional analysis identified treatment patterns from 2016 to 2018. A longitudinal analysis investigated bDMARD utilization (persistence, switch, discontinuing treatment) among bio-naïve patients, with 2014 and 2017 as inclusion periods. Follow-up extended from first bDMARD prescription (index date) to end of data availability. RESULTS: The prevalence of AS was 75.5 per 100,000 (88.3 per 100,000 in adults) in 2018. In total, 5,942 AS patients were identified in 2016, 6,554 in 2017, and 7,146 in 2018. bDMARDs were prescribed to 21.4% (2016), 22.0% (2017), and 16.9% (2018) of the patients. Among the 349 patients included in 2014, 9.5% switched therapies, 13.8% discontinued treatment. In 2017, 12.2% of the 262 patients included switched therapies, 27.1% discontinued treatment. CONCLUSIONS: This study provided an up-to-date prevalence of AS diagnosis in Italy. Bio-naïve patients showed an increasing tendency toward switch of therapy and discontinuation.

Treatment Patterns and Pharmacoutilization in Patients Affected by Psoriasis: An Observational Study in an Italian Real-World Setting.

BACKGROUND: Real-world data can inform the use of biologics for psoriasis (PSO). OBJECTIVE: The aim was to evaluate treatment patterns and analyze pharmacoutilization in PSO patients in a real-world Italian setting, with a focus on the biologics most recently introduced. METHODS: An observational study based on administrative databases was conducted. Patients were included based on PSO diagnosis identified by either discharge diagnosis or exemption code or prescription of anti-psoriatic topical drugs (proxy of diagnosis). To describe patient characteristics and treatment patterns using the most up-to-date data, two different approaches were used: a cross-sectional study performed during 2016-2018, and a longitudinal study conducted with patients who received their first biological/targeted synthetic drugs (naïve patients) in 2014 and 2017 (the inclusion periods). RESULTS: During 2016-2018, the number of prevalent patients diagnosed with PSO was 194,054 (2016), 210,830 (2017), and 225,171 (2018). The percentage of patients receiving biologics or targeted synthetic agents ranged from 1.5 to 2.1%. Among them, naïve patients receiving interleukin (IL) inhibitors increased from 37.5% (2016) to 69.4% (2018), while those receiving anti-tumor necrosis factor (anti-TNF) decreased from 62.5% (2016) to 30.6% (2018). The longitudinal analysis included 894 and 1218 naïve patients in 2014 and 2017, respectively, of whom 7.2% (2014) and 6.9% (2017) switched therapy after a mean of 7.1 (2014) and 6.9 (2017) months. Overall, 259 patients were prescribed ixekizumab starting in 2017, of whom 73% were naïve. Ixekizumab was prescribed as monotherapy to 52.5%. CONCLUSIONS: The proportion of patients receiving biologics appeared constant over the years, with an increasing number of naïve patients being prescribed IL-17 inhibitors. Ixekizumab patients were mostly naïve.

Treatment Patterns and Pharmacoutilization in Patients Affected by Rheumatoid Arthritis in Italian Settings.

This study aimed to evaluate the treatment patterns and pharmacoutilization of patients with rheumatoid arthritis (RA) in real-world settings in Italy. This retrospective observational analysis was based on administrative databases of selected Italian entities. All adult patients with RA diagnosis confirmed by ≥1 discharge diagnosis of RA (ICD-9-CM code = 714.0) or an active exemption code (006.714.0) were enrolled in 2019. Two cohorts were created: one included patients prescribed baricitinib, the other those prescribed biological disease-modifying antirheumatic drugs (bDMARDs). Overall, 47,711 RA patients were identified, most of them without DMARD prescription. As a first-line prescription, 43.2% of patients were prescribed conventional synthetic DMARDs (csDMARDs), 5.2% bDMARDs and 0.3% baricitinib. In 2019, 82.6% of csDMARD users continued with the same DMARD category, 15.9% had a bDMARD, while 1.5% had baricitinib as second-line therapy. Overall, 445 patients used baricitinib during 2019. During follow-up, baricitinib was prescribed as monotherapy to 31% of patients, as cotreatment with csDMARDs and corticosteroids to 27% of patients, with corticosteroids to 28% of patients and with csDMARDs to 14% of patients. In line with previous findings, a trend of bDMARD undertreatment was observed. The treatment patterns of baricitinib patients could help to better characterize patients eligible for new therapeutic options that will be available in the future.

Number needed to treat for interleukin inhibitors approved for the treatment of moderate-to-severe plaque psoriasis in Italy.

Background: Interleukin (IL) inhibitors achieve greater levels of efficacy than older systemic therapies. We calculated the number needed to treat (NNT) of ixekizumab compared with other IL inhibitors approved in Italy for the treatment of moderate-to-severe plaque psoriasis. Methods: The clinical efficacy was evaluated in terms of NNT, based on the results of a recent network meta--analysis (NMA) by the Cochrane Database of Systematic Reviews. The NMA investigated many systemic and biological treatments, but this analysis compared only the efficacy of the following IL inhibitors - brodalumab, guselkumab, ixekizumab, risankizumab, secukinumab, tildrakizumab and ustekinumab - for patients with moderate-to-severe plaque psoriasis. Drugs were compared and ranked according to effectiveness considering the PASI (Psoriasis Area and Severity Index) 90 score. Results: One-hundred and forty trials (51,749 patients) were included in the NMA. Considering the proportion of patients who achieve PASI90, ixekizumab showed the lowest NNT among all comparators (ixekizumab 2.01 [2.46-3.00]; risankizumab 2.05 [2.50-3-05]; guselkumab 2.16 [2.68-3.36]; secukinumab 2.40 [2.90-3.51]; brodalumab 2.61 [3.18-3.88]; ustekinumab 3.44 [4.12-4.95]; tildrakizumab 3.10 [4.15-5.59]. Conclusion: The findings show that ixekizumab is the most effective option (NNT) for the treatment of moderate-to-severe plaque psoriasis.

Real-World Analysis of Therapeutic Patterns in Patients Affected by Rheumatoid Arthritis in Italy: A Focus on Baricitinib.

INTRODUCTION: The objective of this study was to evaluate treatment patterns in patients with rheumatoid arthritis (RA), with a focus on the utilization of baricitinib, an oral highly selective Janus kinase 1 and 2 inhibitor, in an Italian real-world setting. METHODS: This observational retrospective analysis was based on data collected in selected Italian administrative databases. Patients aged ≥ 18 years with a diagnosis of RA defined by hospitalization discharge diagnosis (International Classification of Diseases, Ninth Revision, Clinical Modification code 714.0) or by disease exemption code 006 for RA in 2018 were included. The index date (ID) was defined as the date of first prescription for a drug indicated for RA during the inclusion period. Patients without a prescription for biologic/targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) before the ID were considered to be b/tsDMARD naïve. A further analysis was performed on patients only receiving baricitinib. RESULTS: A total of 41,290 RA patients were enrolled, of whom 55.6% were not treated with conventional synthetic DMARDs (csDMARDs) or b/tsDMARDs, 39.4% were receiving therapy with csDMARDs, and 5.0% were using b/tsDMARDs. In the latter group, 2.7% (n = 56) were receiving therapy with baricitinib. In 2018, 13.2% of csDMARD-treated patients switched to b/tsDMARDs, of whom 4.3% (n = 93) of these switched to baricitinib. In total, 149 patients (mean age ± standard deviation 57.6 ± 12.1; 12.8% male) had a baricitinib prescription, of whom 51% were b/tsDMARD naïve. At baseline, 61.7% of baricitinib users were receiving combination therapy with csDMARDs plus corticosteroids, 26.2% were receiving combination therapy with corticosteroids, and 8.1% were receiving combination therapy with csDMARDs; 4% were receiving baricitinib monotherapy. During follow-up, the proportion of patients receiving baricitinib monotherapy increased to 38.9%, while 26.9, 18.8, and 15.4% of baricitinib users received combination therapy with corticosteroids, csDMARDs plus corticosteroids, and csDMARDs, respectively. CONCLUSION: This study provides a current view of the treatment patterns in Italian patients with RA in a real-world setting of daily clinical practice, with a focus on baricitinib utilization.

Treatment patterns, health care resource utilization and costs of rheumatoid arthritis patients in Italy: findings from a retrospective administrative database analysis.

OBJECTIVES: This study aimed to: 1) describe treatment patterns and drug utilization profile (in terms of therapeutic strategy used, switch, persistence and drug consumption variation) among adult patients affected by rheumatoid arthritis (RA), and 2) estimate the health care resource utilization and its associated direct cost for the management of RA patients. METHODS: A retrospective cohort analysis, using administrative databases of six Local Health Units in Italy, was performed. All adult patients with a confirmed diagnosis of RA between January 1, 2010 and December 31, 2014 were enrolled. The date of the first RA diagnosis according to the study criteria during the study period represented the index date (ID) for each patient. Patients enrolled were observed from the ID for at least 12 months (follow-up period), and their clinical characteristics were investigated for 12 months prior to the ID. RESULTS: A total of 10,401 patients with a confirmed RA diagnosis were included. Mean age was 63.0 years and 25% were male; 67% of patients were untreated at ID. During the followup period, 67.8% of patients treated with biologic agents were persistent with initial therapy, compared to 45.7% for patients on conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), while 11% of patients treated with biologic agents switched during the follow-up period, compared to 17.6% of csDMARDs-treated ones. At the end of the follow-up period, 14.7% of all patients in the analysis had an increase and 12.6% of them had a decrease in their initial drug consumption. The mean cost per RA patient was €3,743. CONCLUSION: Our study showed that there is still much that needs to be learned about the prescription of csDMARDs and biologics to RA patients in Italy and to identify areas for future research. The knowledge of RA management in a real-life clinical setting could offer an opportunity to improve the management of RA in Italy.

Phylogenetic plant community structure along elevation is lineage specific.

The trend of closely related taxa to retain similar environmental preferences mediated by inherited traits suggests that several patterns observed at the community scale originate from longer evolutionary processes. While the effects of phylogenetic relatedness have been previously studied within a single genus or family, lineage-specific effects on the ecological processes governing community assembly have rarely been studied for entire communities or flora. Here, we measured how community phylogenetic structure varies across a wide elevation gradient for plant lineages represented by 35 families, using a co-occurrence index and net relatedness index (NRI). We propose a framework that analyses each lineage separately and reveals the trend of ecological assembly at tree nodes. We found prevailing phylogenetic clustering for more ancient nodes and overdispersion in more recent tree nodes. Closely related species may thus rapidly evolve new environmental tolerances to radiate into distinct communities, while older lineages likely retain inherent environmental tolerances to occupy communities in similar environments, either through efficient dispersal mechanisms or the exclusion of older lineages with more divergent environmental tolerances. Our study illustrates the importance of disentangling the patterns of community assembly among lineages to better interpret the ecological role of traits. It also sheds light on studies reporting absence of phylogenetic signal, and opens new perspectives on the analysis of niche and trait conservatism across lineages.

Severe acute respiratory syndrome coronavirus elicits a weak interferon response compared to traditional interferon-inducing viruses.

The aim of the present study is to investigate changes of interferon (IFN) production occurring over the first 48 h after infection of peripheral blood mononuclear cells (PBMCs) with severe acute respiratory syndrome (SARS) coronavirus (CoV) and to compare these changes to those induced by well-established IFN-inducing viruses, such as vesicular stomatitis (VSV) and Newcastle viruses (NDV). Experiments have been carried out using PBMCs of 10 different healthy donors. The results showed that the antiviral activity of IFN contained in the supernatant of SARS-CoV-infected PBMCs was lower than those induced by VSV and NDV. Consequently, SARS-CoV induces a lower synthesis of IFN-alpha, -beta and -gamma compared to VSV and NDV. Characterization of the profile of IFN-alpha subtypes genes expression in SARS-CoV-infected PBMCs demonstrated that the level of IFN-alpha2 and -6 subtypes were higher compared to other IFN-alpha subtypes namely, IFN-alpha5, -8, -10, -13/1, -17, and -21. In conclusion, SARS-CoV induces IFNs to a less extent compared to VSV and NDV, thus suggesting that the IFN system does play a limited role in early host defense against SARS-CoV infection.