ObjectiveWe aimed to evaluate the drug retention rate (DRR) of secukinumab, an anti-IL-17A monoclonal antibody, in patients with psoriatic arthritis (PsA) in a real-life cohort, and to assess the impact of comorbidities and patient clinical characteristics on the DRR of secukinumab.Methods A retrospective study of prospective followed-up patients was performed to evaluate the DRR of secukinumab on patients with PsA attending the recruiting centres between January 2016 and June 2022. ResultsIn 207 patients with PsA, a 60-month DRR of secukinumab of 57.0% was estimated (mean time of administration of 21.5±17.1 months). Male gender, age ≥65 years, disease duration ≥5 years and ≥10 years did not influence the DRR of secukinumab. The presence of comorbidities, considering any concomitant disorder, did not affect the DRR of secukinumab. In patients with cardiometabolic multimorbidity, a trend toward a better DRR of secukinumab was recorded. In fact, patients with high blood pressure, dyslipidaemia, and type 2 diabetes showed a trend toward an improved DRR of secukinumab. Furthermore, the presence of obesity did not influence the DRR of secukinumab.Different dosages, previous bDMARDs, and concomitant therapy with csDMARDs did not influence the DRR of secukinumab. ConclusionA cumulative 60-month DRR of secukinumab of 57.0% in patients with PsA was retrieved. The presence of cardiometabolic multimorbidity could be associated with an improved DRR of secukinumab, whereas obesity did not affect this feature in our cohort. Previous bDMARDs, concomitant csDMARDs, and different drug dosages could not influence the DRR of secukinumab over time.

The aims of this systematic literature review (SLR) were to identify the effects of approved biological and targeted synthetic disease modifying antirheumatic drugs (b/tsDMARDs) on synovial membrane of psoriatic arthritis (PsA) patients, and to determine the existence of histological/molecular biomarkers of response to therapy. A search was conducted on MEDLINE, Embase, Scopus, and Cochrane Library (PROSPERO:CRD42022304986) to retrieve data on longitudinal change of biomarkers in paired synovial biopsies and in vitro studies. A meta-analysis was conducted by adopting the standardized mean difference (SMD) as a measure of the effect. Twenty-two studies were included (19 longitudinal, 3 in vitro). In longitudinal studies, TNF inhibitors were the most used drugs, while, for in vitro studies, JAK inhibitors or adalimumab/secukinumab were assessed. The main technique used was immunohistochemistry (longitudinal studies). The meta-analysis showed a significant reduction in both CD3+ lymphocytes (SMD −0.85 [95% CI −1.23; −0.47]) and CD68+ macrophages (sublining, sl) (SMD −0.74 [−1.16; −0.32]) in synovial biopsies from patients treated for 4–12 weeks with bDMARDs. Reduction in CD3+ mostly correlated with clinical response. Despite heterogeneity among the biomarkers evaluated, the reduction in CD3+/CD68+sl cells during the first 3 months of treatment with TNF inhibitors represents the most consistent variation reported in the literature.

Background:Antiphospholipid (aPL) antibodies are considered in obstetric morbidity even when Sydney criteria for OAPS are not met. Classification and treatment of NC-OAPS patients and aPL carriers during pregnancy are still debated.Objectives:To increase knowledge, we evaluated and compared aPL serum profiles, exposure to antithrombotic therapies and pregnancy outcomes in OAPS, NC-OAPS and aPL carrier patients, accessing to our centre.Methods:A retrospective observational study was conducted on pregnant outpatients from January 2003 to April 2020. According to Sydney revised classification criteria, we considered lupus anticoagulant (LA), IgM and IgG anti-cardiolipin antibodies (aCL), IgM and IgG antibeta2 glycoprotein I antibodies (aβ2-GPI), to stratify aPL risk profiles [Ref]. In each pregnancy, after case stratification into high (≥ 2 aPL or LA serum positivity) versus low (single aPL positivity) risk profile, we evaluated antithrombotic treatment strategy and subsequent pregnancy outcomes as live-births, spontaneous abortions (SA) or foetal losses.Results:A total of 78 pregnancies were followed: 17 in OAPS, 9 in NC-OAPS and 52 in aPL carrier patients. Rheumatic diseases (RD) coexisted predominately in carriers (73.1%), mainly systemic lupus erythematosus (57.9%). As presented in Table 1, in OAPS and aPL plus RD carrier groups the association of acetyl-salicylic acid (ASA - mean dose 100 mg q.d.) and low-molecular weight heparin (LMWH - mean dose 4000 UI q.d.) showed a better rate of positive outcomes (97.8% of pregnancies) in high aPL risk profile, compared to monotherapy, especially with LA or triple aPL positivity. Conversely, negative outcomes occurred mostly with triple aPL positivity in the first group and double aPL in the second, despite therapy approaches. No significant data were obtained in NC-OAPS group, due to its paucity, though adverse outcomes were observed with monotherapy both in high and low risk profiles. Except aPL carriers with RD, in all other low risk subgroups, a prevalence of negative outcomes occurred using ASA alone, without statistical significance (OR 0; p= 0.45). Similarly, considering the whole population, the use of a mono or a combination therapy in high risk subgroups had not a significant correlation with pregnancy outcomes (OR 1.79; 95%CI 0.31-10.15; p= 0.50).Conclusion:In our study, negative pregnancy outcomes were sporadic, occurring mostly with ≥ 2 aPL positivity. Combination treatment showed better results overall in high aPL risk profile patients, both in OAPS and NC-OAPS or aPL carriers. Though no significant correlation between outcomes and treatments were found, we hinted how aPL-based risk stratification may be useful in adopting personalised therapies to prevent obstetric failures.Reference:[1]Miyakis S, et al (2006) International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome. J Thromb Haemost 4:295–306.Table 1.Population groups, aPL risk profiles, antithrombotic therapies and pregnancy outcomes.Population groupaPL risk profileType/n° of aPLTherapy (n° of pregnancies)Pregnancy outcomesOAPSHighLAASA (1)ASA + LMWH (1)1 live-birth1 live-birth2 aPLASA + LMWH (3)3 live-births3 aPLASA + LMWH (9)7 live-births 2 foetal lossesLow1 aPLASA (2)ASA + LMWH (1)1 live-birth1 foetal loss1 live-birthNC-OAPSHighLA--2 aPLASA (1)LMWH (1)1 live-birth1 SA3 aPL--Low1 aPLASA (6)ASA + LMWH (1)5 live-births1 SA1 live-birthaPL carriers without RDHighLAASA (1)LMWH (1)1 live-birth1 live-birth2 aPLASA (1)LMWH (2)1 live-birth2 live-births3 aPLASA (1)ASA + LMWH (3)1 live-birth3 live-birthsLow1 aPLASA (5)4 live-births1 foetal lossaPL carriers with RDHighLAASA (4)ASA + LMWH (7)3 live-birth1 foetal loss6 live-births1 SA2 aPLASA (6)ASA + LMWH (4)6 live-births2 live-births1 SA1 foetal loss3 aPLLMWH (2)ASA + LMWH (5)2 live-births5 live-birthsLow1 aPLASA (8)ASA + LMWH (3)8 live-births3 live-birthsDisclosure of Interests:None declared