Objective To explore the impact of the human leucocyte antigen (HLA)-B27 on the effectiveness of tumor necrosis factor inhibitors (TNFi) in patients with axial spondyloarthritis (axSpA). Methods A total of 1109 patients with available HLA-B27 status (831 B27+ patients and 278 B27− patients) fulfilling the Assessment of Spondyloarthritis international Society classification criteria for axSpA from the prospective Swiss Clinical Quality Management Registry initiating a first TNFi were included. Drug retention was investigated with multiple adjusted Cox proportional hazard models with imputation of missing values. Multiple-adjusted logistic regression analyses were used to assess the proportion of patients reaching 50% reduction in the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI50) at 1 year. Results B27+ and B27− patients differed with regard to age, sex, BASDAI, C-reactive protein (CRP), body mass index, enthesitis, uveitis, and classification status. After adjustment for potential confounders for the relationship between HLA-B27 and drug effectiveness (sex and family history of spondyloarthritis), a higher risk of drug discontinuation was found in B27− patients (HR 1.53, 95% CI 1.27–1.83). This difference decreased after additional adjustment for parameters which may act as mediators (HR 1.30, 95% CI 1.30–1.55). Male sex and elevated C-reactive protein (CRP) levels were consistently associated with longer retention. Comparable results were obtained for BASDAI50 responses. Conclusion The HLA-B27 genotype is an important predictor of treatment effectiveness. Male sex and CRP seem, however, to better describe variability of response in individual patients. This data may help avoiding potential discrimination of B27− individuals with regard to TNFi initiation. Key Points• HLA-B27 is a predictor of effectiveness of TNF inhibitors in axial spondyloarthritis.• Variability of response in individual patients is better defined by sex and objective markers of disease activity, such as C-reactive protein.
Background Sufficient data on access to systemic treatment for patients with psoriasis living in Latin America (LA) including Chile and Brazil are lacking. Understanding the availability and limiting factors of access to treatments can help to improve patient care and decrease long-term healthcare costs. Objective In association with the Global Psoriasis Atlas, this cross-sectional survey study analysed the availability and insurance reimbursement of systemic treatments for adult psoriasis patients in Brazil and Chile. Methods A multi-centre, cross-sectional ‘Global Healthcare Study on Psoriasis’ (GHSP) was performed in Brazil and Chile in 2020. For each eligible adult psoriasis patient, doctors and nurses completed a 48-item questionnaire about clinical aspects of psoriasis including the Psoriasis Area Severity Index (PASI), Body Surface Area (BSA), and Dermatology Life Quality Index (DLQI), as well as the availability of systemic treatments and insurance reimbursement status. Between-country differences were compared with Wilcoxon rank sum tests for continuous variables, and a chi-square test, or Fisher´s exact test where appropriate, for categorical variables. The median and inter-quartile range (IQR) was calculated for non-normal distributed data. Results A total of 1,424 psoriasis patients from 43 centres, 27 centres in Brazil (n = 826) and 16 in Chile (n = 598), were included with a mean age of 49.1 years (±16.3) and 49.2 years (±15.1) respectively. Unstratified analyses revealed that psoriasis patients in Chile had more severe disease than those in Brazil (PASI 11.7 vs. 8.4 (p < 0.001) and BSA 14.7 vs. 12.0 (p = 0.003) respectively). For patients with moderate-to- severe psoriasis, defined as PASI and/or BSA ≥ 10, systemic non-biologic drugs were available (81.2% in Brazil and 65.3% in Chile, p ≤ 0.001), but only 37.0% of patients in Brazil and 27.3% in Chile received biologics (p = 0.01). Lack of availability and/or lack of insurance reimbursement for biological drugs for moderate-to-severe psoriasis patients was reported for 22.2% (50 out of 357) in Brazil and 67.9% (148 out of 300) in Chile (p < 0.001). Patients with no access to biologic therapies due to lack of availability/insurance reimbursement had a median PASI of 9.15 (IQR 3.00, 14.25) in Brazil and 12.0 (IQR 5.00, 19.00) in Chile (p = 0.007), as well as a median BSA of 7.0 (IQR 3.00, 15.00) and 12.0 (IQR 5.00, 22.50) (p = 0.002), and median DLQI of 11.0 (6.00, 15.00) and 21.0 (6.50, 25.00) (p = 0.007) respectively. Conclusion Chilean patients had significantly more severe psoriasis compared to Brazilian patients in our study. While non-biologic treatments for moderate-to-severe psoriasis were available in both Latin American countries, there is a high need for an improvement in access to more effective psoriasis treatment including biologics. Our results highlight a significant gap between treatment recommendations in international psoriasis guidelines and real-world situations in Brazil and Chile.
Novel treatment modalities comprising immune checkpoint inhibitors and targeted therapies have revolutionized treatment of metastatic melanoma. Still, some patients suffer from rapid progression and decease within months after a diagnosis of stage IV melanoma. We aimed to assess whether genomic alterations may predict survival after the development of stage IV disease, irrespective of received therapy. We analyzed tumor samples of 79 patients with stage IV melanoma using a custom next-generation gene-sequencing panel, MelArray, designed to detect alterations in 190 melanoma-relevant genes. We classified the patients: first, as short survivors (survival ≤6 months after stage IV disease, n = 22) and long survivors (survival >6 months, n = 57); second, by using a cut-off of one year; and third, by comparing the longest surviving 20 patients to the shortest surviving 20. Among analyzed genes, no individual gene alterations, or combinations of alterations, could be dichotomously associated with survival. However, the cohort’s mutational profiles closely matched three known mutational signatures curated by the Catalog of Somatic Mutations in Cancer (COSMIC): UV signature COSMIC_7 (cosine-similarity 0.932), clock-like signature COSMIC_5 (cosine-similarity 0.829), and COSMIC_30 (cosine-similarity 0.726). Patients with UV signature had longer survival compared to patients with clock-like and COSMIC 30 (p < 0.0001). Subgroup dichotomization at 6 months showed that 75% of patients with UV signature survived longer than 6 months, and about 75% of patients with clock-like signature survived less than 6 months after development of stage IV disease. In our cohort, clock-like COSMIC_5 mutational signature predicted poor survival while a UV signature COSMIC_7 predicted longer survival. The prognostic value of mutational signatures should be evaluated in prospective studies.
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