biologic therapy

生物治疗
  • 文章类型: Journal Article
    背景:类风湿性关节炎(RA)患者可根据发病年龄分为晚发性RA≥60岁或早发性RA<60岁。目前的治疗指南没有规定任何关于迟发性组应首先使用的生物制剂的偏好。这项研究旨在比较晚期和早发性RA患者首次生物治疗的药物存活时间。
    方法:这是一项基于人群的队列研究,使用Leumit医疗服务的医疗记录。我们纳入了2000年至2017年间所有符合条件的RA患者。将RA患者分为迟发性和早发性RA组,并根据首次生物治疗的药物生存时间进行比较。
    结果:最终队列包括3814例RA患者,其中2807人(73.6%)患有早发性RA。总的来说,与迟发性患者相比,早发性患者更经常使用生物疾病改善抗风湿药(bDMARDs)(16.9%vs.7.8%,p<0.001)。在早发患者中,依那西普与第一种生物制剂中最长的药物存活时间有关,在晚发型患者中,阿达木单抗和英夫利昔单抗与最长的药物生存时间相关.在第一个bDMARD的晚期和早期发作患者之间的药物生存时间没有观察到差异,在早发型患者中,除了abatacept和golimumab具有更长的药物生存时间。
    结论:晚发性RA患者接受生物制剂治疗的程度低于早发性RA患者,但两组在首次bDMARD时的药物存活时间没有差异.
    BACKGROUND: Rheumatoid arthritis (RA) patients can be divided according to the age of disease onset and classified as late-onset RA ≥ 60 years old or early-onset RA < 60 years old. Current treatment guidelines do not stipulate any preference regarding the biologic that should be used first in the late-onset group. This study aims to compare the drug survival times on first biological treatment between late and early-onset RA patients.
    METHODS: This is a population based cohort study using the medical records of Leumit healthcare services. We included all eligible RA patients between 2000 and 2017. RA patients were divided into late- and early-onset RA groups and compared according to drug survival time on the first biological therapy.
    RESULTS: The final cohort included 3814 RA patients, 2807 (73.6%) of whom had early-onset RA. Overall, biologic disease-modifying anti-rheumatic drugs (bDMARDs) were used more often among early-onset compared to late-onset patients (16.9% vs. 7.8%, p < 0.001). Among early-onset patients, etanercept was associated with the longest drug survival time on the first biologic, and adalimumab and infliximab were associated with the longest drug survival times among late-onset patients. No differences were observed in drug survival times between late and early-onset patients on the first bDMARD, except for abatacept and golimumab with longer drug survival time among early-onset patients.
    CONCLUSIONS: Late-onset RA patients were treated with biologics to a lesser extent than early-onset patients, but no differences were observed in drug survival times at the first bDMARD between the two groups.
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  • 文章类型: Journal Article
    本研究旨在评估炎症性肠病(IBD)患者皮下生物治疗的依从性和不依从性的影响,包括在设有综合专业药房的学术中心的风险因素和结果。
    这是一个多中心,回顾性队列分析在3家拥有综合专业药房的三级护理门诊IBD诊所接受护理的≥18岁患者.受试者被处方注射抗TNF治疗(阿达木单抗,赛托珠单抗,戈利木单抗)或抗IL12/23疗法(ustekinumab),至少连续3次处方索赔。主要结果是药物占有比(MPR),达到最佳依从性的百分比(MPR>0.86);此外,我们试图验证包括吸烟状况在内的先前风险因素模型,麻醉剂使用,精神病史,和先前的生物用途。次要结果包括急诊就诊(ED)和IBD相关住院。采用Wilcox秩和检验进行统计分析。皮尔森卡方检验,而逻辑回归模型是一个无序的,因素变量来灵活地估计坚持的概率。
    纳入了68名受试者。总体中位数MPR为0.95(四分位距0.47,1),依从性为68%-70%。当不依从的危险因素数量增加时,不依从的可能性增加(P<0.05)。在未调整和调整的分析中,不依从性增加了ED访视[比率1.45(95%置信区间1.05,1.97)]和住院[比率1.60(95%置信区间1.16,2.10)]的可能性.
    拥有综合药房的学术中心依从性高。在这个多中心模型中,不依从的先前风险因素仍然很重要。非依从性与住院和ED就诊的可能性更高相关。
    UNASSIGNED: This study aimed to evaluate adherence to subcutaneous biologic therapy and impact of nonadherence including risk factors and outcomes in academic centers with integrated specialty pharmacies for patients with inflammatory bowel disease (IBD).
    UNASSIGNED: This was a multicenter, retrospective cohort analysis of patients aged ≥18 years receiving care in 3 tertiary care outpatient IBD clinics with integrated specialty pharmacies. Subjects were prescribed injectable anti-TNF therapy (adalimumab, certolizumab, golimumab) or anti-IL 12/23 therapy (ustekinumab) with at least 3 consecutive prescription claims. The primary outcomes were medication possession ratio (MPR), percent achieving optimal adherence (MPR > 0.86); in addition, we sought to verify a prior risk factor model including smoking status, narcotic use, psychiatric history, and prior biologic use. Secondary outcomes included emergency department visits (ED) and IBD-related hospitalizations. Statistical analysis was performed using Wilcox rank sum test, Pearson\'s Chi-squared test, and logistic regression model as an unordered, factor variable to flexibly estimate the probabilities of adherence.
    UNASSIGNED: Six hundred eight subjects were included. Overall median MPR was 0.95 (interquartile range 0.47, 1) and adherence was 68%-70%. When the number of risk factors for nonadherence increased, the likelihood of nonadherence increased (P < .05). In unadjusted and adjusted analysis, nonadherence increased the likelihood of ED visits [rate ratio 1.45 (95% confidence interval 1.05, 1.97)] and hospitalizations [rate ratio 1.60 (95% confidence interval 1.16, 2.10)].
    UNASSIGNED: Academic centers with integrated pharmacies had high adherence. Prior risk factors for nonadherence remained significant in this multicenter model. Nonadherence was associated with higher likelihood of hospitalizations and ED visits.
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  • 文章类型: Journal Article
    慢性炎症性疾病(CID)的患病率和疾病负担预计将上升。患者通常用生物制剂治疗,但是个体的治疗反应各不相同,保证进一步研究优化治疗策略。本研究旨在比较基于吸烟状况开始生物治疗的CIDs患者的临床治疗反应,CIDS中臭名昭著的危险因素。在这项多中心队列研究中,包括233名诊断为克罗恩病的患者,溃疡性结肠炎,类风湿性关节炎,轴性脊柱关节炎,银屑病关节炎或牛皮癣开始生物治疗,我们比较了14~16周后的治疗缓解率和吸烟者与非吸烟者的次要结局.我们使用逻辑回归模型评估了组间的对比:(I)一个“粗略”模型,仅针对CID类型进行了调整,和(Ii)调整后的模型(包括性别和年龄)。在符合这项研究条件的205名患者中,53(26%)为吸烟者。吸烟者的治疗反应率(n=23[43%])低于非吸烟者CID人群(n=92[61%]),对应于“粗”OR为0.51(95%CI:[0.26;1.01]),同时调整性别和年龄,结果一致:0.51[0.26;1.02]。在38例RA患者中,对比明显最为突出,在“粗”模型和校正模型中,吸烟者的治疗反应率均显着降低(校正OR0.13,[0.02;0.81])。尽管存在很大的残余混杂风险,应告知CIDs(尤其是类风湿性关节炎)患者吸烟可能会降低对生物治疗产生足够反应的几率.注册:临床。Trials.govNCT03173144.
    The prevalence and disease burden of chronic inflammatory diseases (CIDs) are predicted to rise. Patients are commonly treated with biological agents, but the individual treatment responses vary, warranting further research into optimizing treatment strategies. This study aimed to compare the clinical treatment responses in patients with CIDs initiating biologic therapy based on smoking status, a notorious risk factor in CIDs. In this multicentre cohort study including 233 patients with a diagnosis of Crohn\'s disease, ulcerative colitis, rheumatoid arthritis, axial spondyloarthritis, psoriatic arthritis or psoriasis initiating biologic therapy, we compared treatment response rates after 14 to 16 weeks and secondary outcomes between smokers and non-smokers. We evaluated the contrast between groups using logistic regression models: (i) a \"crude\" model, only adjusted for the CID type, and (ii) an adjusted model (including sex and age). Among the 205 patients eligible for this study, 53 (26%) were smokers. The treatment response rate among smokers (n = 23 [43%]) was lower compared to the non-smoking CID population (n = 92 [61%]), corresponding to a \"crude\" OR of 0.51 (95% CI: [0.26;1.01]) while adjusting for sex and age resulted in consistent findings: 0.51 [0.26;1.02]. The contrast was apparently most prominent among the 38 RA patients, with significantly lower treatment response rates for smokers in both the \"crude\" and adjusted models (adjusted OR 0.13, [0.02;0.81]). Despite a significant risk of residual confounding, patients with CIDs (rheumatoid arthritis in particular) should be informed that smoking probably lowers the odds of responding sufficiently to biological therapy. Registration: Clinical.Trials.gov NCT03173144.
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  • 文章类型: Journal Article
    在这项原始研究中,我们在实际临床实践中介绍了bimekizumab治疗化脓性汗腺炎的有效性和安全性。结果表明,在第16周时,所有活动评分和患者报告的结果均有显着改善,包括平均IHS4从27.1降至15.6(p<0.001),HS-PGA从5.1到3.2(p<0.001),VAS疼痛从8.3到4.7(p<0.001),DLQI从21.6到12.6(p<0.001)。Bimekizumab,每2或4周服用一次,耐受性良好,没有停药,也没有发现新的安全问题。这些发现证实了药物在3期临床试验中观察到的有效性和良好的安全性。支持其在实际临床实践中用于治疗HS。
    In this original research, we present the results in terms of effectiveness and safety of bimekizumab for hidradenitis suppurativa in real clinical practice. Results indicated significant improvement in all activity scores and patient-reported outcomes at week 16, including a notable decrease in mean IHS4 from 27.1 to 15.6 (p < 0.001), HS-PGA from 5.1 to 3.2 (p < 0.001), VAS pain from 8.3 to 4.7 (p < 0.001) and DLQI from 21.6 to 12.6 (p < 0.001). Bimekizumab, administered every 2 or 4 weeks, was well-tolerated with no discontinuations and no new safety concerns identified. These findings corroborate the drug\'s effectiveness and favourable safety profile observed in phase 3 clinical trials, supporting its use in real-world clinical practice for treating HS.
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  • 文章类型: Letter
    暂无摘要。
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  • 文章类型: Journal Article
    背景:现在人们认识到,银屑病在几种合并症的发展中起着关键作用,比如心血管疾病,和代谢综合征。一些作者假设牛皮癣患者患某些类型癌症的风险可能增加。生物药物的有效性和安全性在临床试验和现实生活中都有很好的记录。然而,关于牛皮癣癌症患者使用生物治疗的安全性的证据有限,并且在已经存在或伴随恶性肿瘤的患者中使用该治疗类别仍存在争议。方法:我们在那不勒斯费德里科大学皮肤科诊所对一组接受生物治疗的中重度银屑病肿瘤患者进行了回顾性观察研究。在2016年至2024年期间。我们纳入了20例成年患者;其中15例肿瘤的诊断先于生物学治疗开始,而这些患者中有四名在生物制剂治疗过程中被诊断出患有癌症。结果:我们人群中最常见的肿瘤是乳腺癌,前列腺癌,甲状腺癌,和慢性淋巴白血病.抗IL17药物是最常见的处方(47.7%),其次是抗IL23p19(36.8%),抗IL-12/23(10.5%)和抗TNFα(5.26%)。所有患者在开始治疗后显示银屑病的改善。结论:我们的经验支持在有癌症史或近期起病瘤形成的银屑病患者中生物治疗的有效性和安全性。
    Background: It is now recognized that psoriasis plays a key role in the development of several comorbidities, such as cardiovascular disease, and metabolic syndrome. Some authors have hypothesized that patients with psoriasis may have an increased risk of developing certain types of cancer. The efficacy and safety of biologic drugs are well-documented in clinical trials and in real-life studies. However, there is limited evidence on the safety of the use of biologic treatments in cancer patients with psoriasis, and the use of this therapeutic class in patients with a pre-existing or concomitant malignancy is still debated. Methods: We have conducted a retrospective observational study of a group of oncology patients with moderate-to-severe psoriasis treated with biologic therapy at the Dermatology Clinic of the University of Naples Federico II, during the period from 2016 to 2024. We included 20 adult patients; in 15 of them the diagnosis of neoplasm preceded the start of treatment biologic, while four of these patients had been diagnosed with cancer during the course of therapy biologics. Results: The most represented neoplasms in our population were breast carcinoma, prostate carcinoma, thyroid carcinoma, and chronic lymphatic leukemia. Anti-IL17 drugs were the most frequently prescribed (47.7%), followed by anti-IL23p19 (36.8%), anti-IL-12/23 (10.5%) and anti-TNF alpha (5.26%). All patients showed improvement of psoriasis after starting the therapy. Conclusions: Our experience supports the effectiveness and safety of biological therapy for psoriasis in patients with a history of cancer or recent onset neoplasia.
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  • 文章类型: Journal Article
    背景:本研究的目的是描述与需要免疫抑制治疗的免疫或特发性疾病相关的葡萄膜炎患者的特征以及在实际临床实践中对此类治疗的反应。
    方法:观察性,描述性,描述性纵向,我们对一组被诊断为非感染性葡萄膜炎的患者进行了回顾性研究.为了评估对治疗的反应,我们评估了视力的变化,玻璃体炎,和黄斑水肿的存在。
    结果:我们纳入了356例患者。总的来说,12%需要全身性皮质类固醇治疗,66例患者(18.5%)需要免疫抑制/生物治疗,甲氨蝶呤是最常用的(55%)。应用免疫抑制药物59例(56例,作为首选治疗,3例患者作为生物制剂治疗后的第二选择)。66例患者中有10例(15%)是首选生物制剂治疗,34(48%)在疾病期间的某个时候需要它们,阿达木单抗是最常用的。35名患者(53%)由于对第一种药物缺乏反应而需要转换药物。不同药物在玻璃体炎的消退和视力改善方面没有差异。
    结论:对于大量非感染性葡萄膜炎患者,必须使用全身性皮质类固醇和免疫抑制/生物制剂。在我们的系列中,托珠单抗在解决黄斑水肿方面显著更有效.
    BACKGROUND: The aim of this study was to describe the characteristics of patients with uveitis associated with an immunologic or idiopathic disease that requires immunosuppressive treatment and the response to such treatments in real clinical practice.
    METHODS: An observational, descriptive, longitudinal, and retrospective study of a cohort of patients diagnosed with noninfectious uveitis was performed. To assess the response to treatment, we evaluated the change in visual acuity, vitritis, and the presence of macular edema.
    RESULTS: We included 356 patients. Overall, 12% required treatment with systemic corticosteroids, and 66 patients (18.5%) required immunosuppressive/biological treatment, with methotrexate being the most used (55%). Immunosuppressive drugs were used in 59 cases (in 56 patients, as the first choice of treatment and for 3 patients as the second choice after treatment with biologics). Treatment with biologics was the first choice in 10 patients out of 66 (15%), and 34 (48%) required them at some time during the disease, with adalimumab being the most commonly used. Thirty-five patients (53%) needed to switch drugs due to a lack of response to the first one. There were no differences between different drugs in the resolution of vitritis and improvement in vision.
    CONCLUSIONS: The use of systemic corticosteroids and immunosuppressive/biologics was necessary for a high number of patients with noninfectious uveitis. In our series, tocilizumab was significantly more effective in the resolution of macular edema.
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  • 文章类型: Journal Article
    背景:托法替尼是一种口服Janus激酶抑制剂,最近被批准用于诱导和维持溃疡性结肠炎(UC)的缓解。
    目的:考虑到抗TNF无应答者的数量,本研究旨在评估52周时托法替尼在中重度UC多重失败患者队列中的有效性和安全性.
    方法:从2021年1月至2023年3月,我们进行了一项前瞻性多中心研究,观察中重度UC成年患者在抗TNF治疗失败后开始服用托法替尼,为期52周。根据结肠切除率评估有效性和安全性,临床缓解和反应,内镜缓解,无类固醇临床缓解,和不良事件发生率。
    结果:我们纳入58例UC患者,年龄42±14.4岁,59%的男性,96.6%左侧或泛结肠炎,谁是失败的单一(65.5%)或多个抗TNF(34.5%)。只有6例(10.3%)患者接受了结肠切除术。结肠切除术在临床上与W8(p=0.023)和W24(p=0.004)时托法替尼10mgbid的必要性和额外周期数相关,并且在W8处有较高的部分Mayo评分(p=0.025)。在W52,临床缓解,临床反应,无类固醇临床缓解率为53.4%,43.1%,和48.3%,分别。在W52进行的22例结肠镜检查中,有11例(50%)显示内窥镜缓解。14例(24.1%)患者发生不良事件,但只有2例(3.4%)导致托法替尼停药.
    结论:在抗TNF难治性UC患者的现实生活中,托法替尼已被证明在52周时可有效预防结肠切除术并诱导临床和内镜缓解,且安全性良好.
    BACKGROUND: Tofacitinib is an oral Janus kinase inhibitor recently approved to induce and maintain remission in ulcerative colitis (UC).
    OBJECTIVE: Considering the number of anti-TNF non-responders, this study aims to assess the effectiveness and safety of tofacitinib in a cohort of multi-failure patients with moderate-to-severe UC at 52 weeks.
    METHODS: From January 2021 to March 2023, we performed a prospective multicenter study observing adult patients with moderate-to-severe UC starting tofacitinib after an anti-TNF failure for a 52-week-long period. Effectiveness and safety were assessed in terms of colectomy rate, clinical remission and response, endoscopic remission, steroid-free clinical remission, and rate of adverse events.
    RESULTS: We included 58 patients with UC with an age of 42 ± 14.4 years, 59% males, 96.6% left-sided or pancolitis, who were failure to a single (65.5%) or more than one anti-TNF (34.5%). Only 6 (10.3%) patients underwent colectomy. Colectomy was clinically associated with the necessity and the number of extra cycles of tofacitinib 10 mg bid at W8 (p = 0.023) and W24 (p = 0.004), and with a higher partial Mayo score at W8 (p = 0.025). At W52, clinical remission, clinical response, and steroid-free clinical remission were 53.4%, 43.1%, and 48.3%, respectively. Of 22 performed colonoscopies at W52, 11 (50%) showed endoscopic remission. Adverse events occurred in 14 (24.1%) patients, but only 2 (3.4%) led to tofacitinib discontinuation.
    CONCLUSIONS: In a real-life setting of patients with anti-TNF refractory UC, tofacitinib has proved to be effective in preventing colectomy and inducing clinical and endoscopic remission at 52 weeks with a good safety profile.
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  • 文章类型: Journal Article
    Takayasu动脉(TAK)是一种慢性炎症性疾病,主要影响主动脉及其主要分支,在婴儿中很少报道。我们旨在总结三级护理中心婴儿TA(I-TA)的临床特征。
    我们进行了一项回顾性研究,涉及10例诊断为TAK的婴儿。临床综合评价,实验室,射线照相特征,疾病活动,进行治疗和结果。
    连续的队列由8个女孩和2个男孩组成,诊断年龄为11.1(1.7-36)个月。中位诊断时间和平均随访时间分别为9.5天(2-235天)和10.9(1-21)个月,分别。最常见的最初表现是不适(80%),发烧(70%),高血压(50%)和皮疹(30%)。平均小儿血管炎活动评分(PVAS),Takayasu临床活动评分(ITAS-2010)和ITAS-A评分分别为2.8/63、2.6/51和5.6/54。所有患者均有异常的实验室参数。最常见的病变是胸主动脉(60%)和腹主动脉(60%)。在大多数情况下(70%)开始使用皮质类固醇联合环磷酰胺,然后长期使用霉酚酸酯。5例尝试使用生物制剂。死亡率为40%。
    及时诊断婴儿的TAK具有挑战性。考虑到涉及的船只越多,更严重的炎症和更高的死亡率,积极的治疗是必要的婴儿。GCs和CYC治疗似乎是有效的。
    UNASSIGNED: Takayasu artery (TAK) is a chronic inflammatory disease that mainly affects the aorta and its major branches and is rarely reported in infants. We aimed to summarize the clinical features of infant TA (I-TA) in a tertiary care center.
    UNASSIGNED: We performed a retrospective study involving 10 infants diagnosed with TAK. A comprehensive evaluation of clinical, laboratory, radiographic features, disease activity, treatment and outcomes was carried out.
    UNASSIGNED: A consecutive cohort was composed of 8 girls and 2 boys, with an age at diagnosis of 11.1 (1.7-36) months. The median time to diagnosis and the average time to follow-up were 9.5 days (2-235 days) and 10.9 (1-21) months, respectively. The most common initial manifestations were malaise (80%), fever (70%), hypertension (50%) and rash (30%). The mean Pediatric Vasculitis Activity Score (PVAS), Takayasu Clinical Activity Score (ITAS-2010) and ITAS-A scores were 2.8/63, 2.6/51, and 5.6/54, respectively. All patients had aberrant laboratory parameters. The most common lesions were in the thoracic aorta (60%) and abdominal aorta (60%). Corticosteroids combined with cyclophosphamide followed by long-term mycophenolate mofetil were initiated in most cases (70%). Biologics were attempted in 5 cases. Mortality was 40%.
    UNASSIGNED: It is challenging to diagnose TAK in infants in a timely manner. Considering the more vessels involved, more severe inflammation and higher mortality, aggressive treatment is warranted in infants. GCs and CYC treatment seem to be effective.
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  • 文章类型: Journal Article
    目的:评估人类白细胞抗原B27(HLA-B27)阳性的强直性脊柱炎(AS)持续炎症患者使用生物疾病缓解抗风湿药(bDMARDs)与恶性肿瘤风险之间的联系。
    方法:在2006年至2021年间,对1445例HLA-B27阳性AS患者进行了回顾性评估。其中,112例患者需要bDMARD治疗。该研究比较了常规治疗与bDMARDs,并调查了发生恶性肿瘤的危险因素。
    结果:在8253患者年的随访中,38例(2.6%)患者出现各种恶性肿瘤,包括肺,肝脏,乳房,还有结肠癌.与接受常规合成DMARDs(csDMARD)和非甾体抗炎药的PS匹配组相比,bDMARD治疗组的恶性肿瘤风险明显更高。随访6年后,恶性肿瘤的累积风险显着增加。所有在bDMARD治疗后发展为恶性肿瘤的患者都接受了肿瘤坏死因子-α抑制剂。需要BDMARD治疗,需要bDMARDs结合CSDMARD治疗,30岁后被诊断为AS是发生恶性肿瘤的独立危险因素.
    结论:需要生物治疗的持续炎症的HLA-B27阳性AS患者,特别是在30岁以后确诊,可能会增加恶性肿瘤的风险.对于这些接受生物治疗的患者,建议定期进行癌症筛查。
    OBJECTIVE: To assess the link between the administration of biologic disease-modifying antirheumatic drugs (bDMARDs) and the risk of malignancy in human leukocyte antigen B27 (HLA-B27)-positive patients with ankylosing spondylitis (AS) experiencing sustained inflammation.
    METHODS: Between 2006 and 2021, 1445 HLA-B27-positive patients with AS were retrospectively evaluated. Among them, 112 patients required bDMARD therapy. The study compared conventional therapy with bDMARDs and investigated the risk factors for developing malignancies.
    RESULTS: During 8253 patient-years of follow-up, 38 (2.6%) patients developed various malignancies, including lung, liver, breast, and colon cancer. The risk of malignancy was significantly higher in the bDMARD-treated group compared to PS-matched groups receiving conventional synthetic DMARDs (csDMARD) and non-steroidal anti-inflammatory drugs. The cumulative risk of malignancies increased significantly after 6 years of follow-up. All patients who developed malignancy after bDMARD therapy received tumor necrosis factor-α inhibitors. Requiring bDMARD therapy, requiring bDMARDs in combination with csDMARD therapy, and being diagnosed with AS after 30 years of age were independent risk factors for developing malignancy.
    CONCLUSIONS: HLA-B27-positive AS patients with sustained inflammation requiring biologic therapy, particularly if diagnosed after age 30, may have an increased risk of malignancy. Regular cancer screenings are advisable for these patients while undergoing biologic treatment.
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