Off-label studies on apremilast in dermatology: a review.
- 作者列表："Maloney NJ","Zhao J","Tegtmeyer K","Lee EY","Cheng K
:Purpose: Apremilast is a phosphodiesterase-4 inhibitor FDA approved for psoriatic arthritis and moderate to severe plaque psoriasis. In recent years, multiple studies have suggested other potential uses for apremilast in dermatology. A summary of these various studies will be a valuable aid to dermatologists considering apremilast for an alternative indication.Materials and methods: The PubMed/MEDLINE and ClinicalTrials.gov databases were queried with the term 'apremilast,' with results manually screened to identify published data on off-label uses of apremilast. The article was structured by the quality of evidence available.Results: Apremilast use in dermatology beyond plaque psoriasis and psoriatic arthritis is frequently described in the literature, with a mixture of positive and negative results. Randomized controlled data is available for Behçet's disease, hidradenitis suppurativa, nail/scalp/palmoplantar psoriasis, alopecia areata, and atopic dermatitis.Conclusion: The relatively safe adverse effect profile of apremilast and its broad immunomodulatory characteristics may make it a promising option in the future for patients with difficult to treat diseases in dermatology, refractory to first line therapies, but further studies will be necessary to clarify its role.
目的: Apremilast是FDA批准用于治疗银屑病关节炎和中重度斑块状银屑病的phosphodiesterase-4 抑制剂。近年来，多项研究提示apremilast在皮肤科的其他潜在用途。这些不同研究的总结将是皮肤科医生考虑apremilast替代适应症的宝贵帮助。材料和方法: 使用术语 “apremilast” 查询PubMed/MEDLINE和ClinicalTrials.gov数据库，结果人工筛选，以确定apremilast非标签使用的已发表数据。这篇文章是由现有证据的质量构成的。结果: 文献中经常描述Apremilast在斑块状银屑病和银屑病关节炎以外的皮肤病学中的使用，阳性和阴性结果混合。可获得白塞病、化脓性汗腺炎、指甲/头皮/掌跖银屑病、斑秃和特应性皮炎的随机对照数据。结论: apremilast相对安全的不良反应特征及其广泛的免疫调节特性可能使其成为未来皮肤科治疗困难、一线治疗无效的患者的一种有前途的选择，但进一步的研究将是必要的，以明确其作用。
METHODS:OBJECTIVE:Patients with immune-mediated inflammatory diseases such as rheumatoid arthritis or systemic lupus erythematosus are at increased risk of cardiovascular disease. However, the cardiovascular risk of patients with primary Sjögren's syndrome (SS) remains poorly studied. We aimed to investigate the association between primary SS and cardiovascular morbidity and mortality. METHODS:We performed a systematic review of articles in Medline and the Cochrane Library and recent abstracts from US and European meetings, searching for reports of randomized controlled studies of cardiovascular morbidity and cardiovascular mortality in primary SS. The relative risk (RR) values for cardiovascular morbidity and mortality associated with primary SS were collected and pooled in a meta-analysis with a random-effects model by using Review Manager (Cochrane collaboration). RESULTS:The literature search revealed 484 articles and abstracts of interest; 14 studies (67,124 patients with primary SS) were included in the meta-analysis. With primary SS versus control populations, the risk was significantly increased for coronary morbidity (RR 1.34 [95% confidence interval (95% CI) 1.06-1.38]; P = 0.01), cerebrovascular morbidity (RR 1.46 [95% CI 1.43-1.49]; P < 0.00001), heart failure rate (odds ratio 2.54 [95% CI 1.30-4.97]; P < 0.007), and thromboembolic morbidity (RR 1.78 [95% CI 1.41-2.25]; P < 0.00001), with no statistically significant increased risk of cardiovascular mortality (RR 1.48 [95% CI 0.77-2.85]; P = 0.24). CONCLUSION:This meta-analysis demonstrates that primary SS is associated with increased cardiovascular morbidity, which suggests that these patients should be screened for cardiovascular comorbidities and considered for preventive interventions, in a multidisciplinary approach with cardiologists.
METHODS:OBJECTIVE:We aimed to evaluate the comparative risk of hospitalized infection among patients with rheumatoid arthritis (RA) who initiated abatacept versus a tumor necrosis factor inhibitor (TNFi). METHODS:Using claims data from Truven MarketScan database (2006-2015), we identified patients with RA ages ≥18 years with ≥2 RA diagnoses who initiated treatment with abatacept or a TNFi. The primary outcome was a composite end point of any hospitalized infection. Secondary outcomes included bacterial infection, herpes zoster, and infections affecting different organ systems. We performed 1:1 propensity score (PS) matching between the groups in order to control for baseline confounders. We estimated incidence rates (IRs) and hazard ratios (HRs) with 95% confidence intervals (95% CIs) for hospitalized infection. RESULTS:We identified 11,248 PS-matched pairs of patients who initiated treatment with abatacept and TNFi with a median age of 56 years (83% were women). The IR per 1,000 person-years for any hospitalized infection was 37 among patients who initiated treatment with abatacept and 47 in those who initiated treatment with TNFi. The HR for the risk of any hospitalized infection associated with abatacept versus TNFi was 0.78 (95% CI 0.64-0.95) and remained lower when compared to infliximab (HR 0.63 [95% CI 0.47-0.85]), while no significant difference was seen when compared to adalimumab and etanercept. The risk of secondary outcomes was lower for abatacept for pulmonary infections, and similar to TNFi for the remaining outcomes. CONCLUSION:In this large cohort of patients with RA who initiated treatment with abatacept or TNFi as a first- or second-line biologic agent, we found a lower risk of hospitalized infection after initiating abatacept versus TNFi, which was driven mostly by infliximab.
METHODS:OBJECTIVE:Reducing pain is one of the main health priorities for children and young people with juvenile idiopathic arthritis (JIA); however, some studies indicate that pain is not routinely assessed in this patient group. The aim of this study was to explore health care professionals' (HCPs) beliefs about the role of pain and the prioritization of its assessment in children and young people with JIA. METHODS:Semi-structured interviews were conducted with HCPs who manage children and young people with JIA in the UK (including consultant and trainee pediatric rheumatologists, nurses, physical therapists, and occupational therapists). Data were analyzed qualitatively following a framework analysis approach. RESULTS:Twenty-one HCPs participated. Analyses of the data identified 6 themes, including lack of training and low confidence in pain assessment, reluctance to engage in pain discussions, low prioritization of pain assessment, specific beliefs about the nature of pain in JIA, treatment of pain in JIA, and undervaluing pain reports. Assessment of pain symptoms was regarded as a low priority and some HCPs actively avoided conversations about pain. CONCLUSION:These findings indicate that the assessment of pain in children and young people with JIA may be limited by knowledge, skills, and attitudinal factors. HCPs' accounts of their beliefs about pain in JIA and their low prioritization of pain in clinical practice suggest that a shift in perceptions about pain management may be helpful for professionals managing children and young people with this condition.