IMPORTANCE Somatic mutations in BAP1 (BRCA1-associated protein 1 gene) are frequently identified in uveal melanoma. To date, the role of germline BAP1 mutations in uveal melanoma has not been characterized. OBJECTIVE To characterize the clinical phenotype of uveal melanoma in patients with germline BAP1 mutations. DESIGN, SETTING, AND PARTICIPANTS Retrospective cohort study at an academic ophthalmology referral center among 507 patients with uveal melanoma who consented for collection of blood samples. The study dates were June 22, 1992, to December 14, 2010. MAIN OUTCOMES AND MEASURES Clinical characteristics of uveal melanoma and the development of metastases. BAP1 gene sequencing from blood samples of patients with uveal melanoma was correlated with clinical characteristics. RESULTS Of 507 blood samples analyzed, 25 patients (4.9%) exhibited 18 BAP1 polymorphisms, of which 9 were novel. Computational analyses predicted that 8 BAP1 mutations in 8 patients (1.6%) were likely to result in damaged BAP1 protein. Five of these 8 mutations were novel. These 8 patients were compared with 482 patients in whom no BAP1 polymorphisms were identified. In univariate analyses, patients with germline BAP1 mutations exhibited larger tumor diameters (mean, 15.9 vs 12.3 mm; P = .004) and higher rates of ciliary body involvement (75.0% vs 21.6%, P = .002) and metastases (71.4% vs 18.0%, P = .003) compared with control subjects. Patients with germline BAP1 mutations exhibited increased frequency of family history of cancer (100% vs 65.9%, P = .06), particularly cutaneous melanoma (62.5% vs 9.9%, P < .001) and ocular melanoma (25.0% vs 1.9%, P = .01). No differences were identified in age at diagnosis, sex, history of other malignant neoplasm, presenting visual acuity, distance of the tumor from the optic nerve or fovea, iris involvement, extrascleral extension, or tumor pigmentation. Germline BAP1 mutations increased risk of metastasis independent of ciliary body involvement (P = .02). Germline BAP1 mutation approached significance as an independent risk factor for metastasis (P = .09). CONCLUSIONS AND RELEVANCE These data suggest that germline BAP1 mutations occur infrequently in uveal melanoma and are associated with larger tumors and higher rates of ciliary body involvement, 2 known risk factors for metastasis.
Background Chronic inflammatory demyelinating polyneuropathy (CIDP) is a rare neurological disorder characterised by muscle weakness and impaired sensory function. The present study provides a comprehensive literature review of the burden of illness of CIDP. Methods Systematic literature search of PubMed, Embase, and key conferences in May 2019. Search terms identified studies on the epidemiology, humanistic burden, current treatment, and economic burden of CIDP published since 2009 in English. Results Forty-five full texts and nineteen conference proceedings were identified on the epidemiology (n = 9), humanistic burden (n = 7), current treatment (n = 40), and economic burden (n = 8) of CIDP. Epidemiological studies showed incidence and prevalence of 0.2-1.6 and 0.8-8.9 per 100,000, respectively, depending on geography and diagnostic criteria. Humanistic burden studies revealed that patients experienced physical and psychosocial burden, including impaired physical function, pain and depression. Publications on current treatments reported on six main types of therapy: intravenous immunoglobulins, subcutaneous immunoglobulins, corticosteroids, plasma exchange, immunosuppressants, and immunomodulators. Treatments may be burdensome, due to adverse events and reduced independence caused by treatment administration setting. In Germany, UK, France, and the US, CIDP economic burden was driven by direct costs of treatment and hospitalisation. CIDP was associated with indirect costs driven by impaired productivity. Conclusions This first systematic review of CIDP burden of illness demonstrates the high physical and psychosocial burden of this rare disease. Future research is required to fully characterise the burden of CIDP, and to understand how appropriate treatment can mitigate burden for patients and healthcare systems.
Background: Real-world studies evaluating patients with challenging-to-treat localizations of psoriasis (scalp, nail, and palmoplantar) are limited. Objective: To characterize patients with versus without psoriasis in challenging-to-treat areas seen in routine US clinical practice. Methods: This retrospective observational study included all adult patients with psoriasis enrolled in the Corrona Psoriasis Registry between April 2015 and May 2018 who initiated a biologic therapy at registry enrollment. Patients were stratified by the presence of scalp, nail, or palmoplantar psoriasis (nonmutually exclusive groups). Patient demographics, clinical characteristics, disease activity, and patient-reported outcome measures (pain, fatigue, itch, EuroQol visual analog scale [EQ VAS], Dermatology Life Quality Index [DLQI], and Work Productivity and Activity Impairment questionnaire [WPAI]) were assessed at registry enrollment and compared between patients with versus without each challenging-to-treat area using nonparametric Kruskal-Wallis tests for continuous variables and χ2 or Fisher exact tests for categorical variables. Generalized linear regression models were used to estimate differences in disease activity and patient-reported outcomes between patients with versus without each challenging-to-treat area. Results: Among 2,042 patients with psoriasis (mean age [±SD], 49.6 ± 14.7 years; 51.5% male), 38.4% had psoriatic arthritis (PsA), 38.1% had scalp psoriasis, 16.0% had nail psoriasis, 10.9% had palmoplantar psoriasis, and 26.2% had a combination of ≥2 challenging-to-treat areas and PsA; only 34.2% had body plaque psoriasis without PsA or challenging-to-treat areas. Patients in all challenging-to-treat groups reported higher (mean [95% CI]) itch (scalp, 58.01 [57.62–58.40] vs. 54.35 [53.99–54.72]; nail, 56.42 [56.02–56.81] vs. 55.59 [55.20–55.97]; palmoplantar, 60.22 [59.86–60.59] vs. 55.15 [54.79–55.54]) and lower EQ VAS (scalp, 68.12 [67.78–68.48] vs. 69.46 [69.12–69.81]; nail, 66.21 [65.89–66.55] vs. 69.48 [69.14–69.83]; palmoplantar, 66.21 [66.07–66.75] vs. 69.29 [68.94–69.94]) scores than those without the respective challenging-to-treat localization. Patients with nail or palmoplantar psoriasis reported higher pain, fatigue, and DLQI scores than those without. Higher proportions of patients with scalp or palmoplantar psoriasis reported work impairment compared with those without. Conclusion: Two-thirds of patients with psoriasis who initiated biologic therapy had PsA and/or ≥1 challenging-to-treat area. Patients with challenging-to-treat areas had worse patient-reported outcome scores than those without, indicating a significant burden of challenging-to-treat areas on patients’ quality of life.
Objective Comorbidity burden and obesity may affect treatment response in patients with rheumatoid arthritis (RA). Few real-world studies have evaluated the impact of comorbidity burden or obesity on the effectiveness of tocilizumab (TCZ). This study evaluated TCZ effectiveness in treating RA patients with high versus low comorbidity burden and obesity versus non-obesity in US clinical practice. Methods Patients in the Corrona RA registry who initiated TCZ were stratified by low or high comorbidity burden using a modified Charlson Comorbidity Index (mCCI) and by obese or nonobese status using body mass index (BMI). Improvements in disease activity and functionality after TCZ initiation were compared for the aforementioned strata of patients at 6 and 12 months after adjusting for statistically significant differences in baseline characteristics. Results We identified patients with high (mCCI ≥ 2; n = 195) and low (mCCI < 2; n = 575) comorbidity burden and patients categorized as obese (BMI ≥ 30; n = 356) and nonobese (BMI < 30; n = 449) who were treated with TCZ. Most patients (> 95%) were biologic experienced and approximately one-third of patients received TCZ as monotherapy, with no significant differences between patients by comorbidity burden or obesity status. Improvement in disease activity and functionality at 6 and 12 months was similar between groups, regardless of comorbidity burden or obesity status. Conclusion In this real-world analysis, TCZ was frequently used to treat patients with high comorbidity burden or obesity. Effectiveness of TCZ did not differ by comorbidity or obesity status.
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