Coronavirus disease 2019(COVID-19) is prevalent around the world, and pre-existing ILD is associated with increased severity and mortality of COVID-19. However, the current knowledge on the management strategy for COVID-19 patients with pre-existing interstitial lung disease (ILD) is very limited. There is still a need for consensus on treatments for these patients. In addition, ILD that occurs after the acute phase of COVID-19 (Post-acute Covid-19 ILD, PC-ILD) is also very common, and how to manage PC-ILD is also under debate. Therefore, a consensus was established by experts from the related disciplines in the field of ILD based on available scientific evidence and experience of the expert working group. This consensus elucidated 22 practical questions for practicing physicians, such as clinical characteristics, risk factors and treatment of COVID-19 patients with pre-existing ILD and PC-ILD patients. Finally, 15 recommendations were made regarding the diagnosis and management of COVID-19 patients with pre-existing ILD and PC-ILD patients. We hope to assist physicians in making appropriate decisions, thereby improving the management of COVID-19 with pre-existing ILD and PC-ILD.Recommendation 1: It is recommended to differentiate COVID-19 from ILD with acute/subacute onset based on duration, exposure history, symptoms and signs, chest high-resolution CT (HRCT) features, and laboratory tests.Recommendation 2: According to the guidelines on the diagnosis and treatment of new coronavirus pneumonia (version 10) issued by the National Health Commission of China on January 6th, 2023, we recommended the following disease severity definition and management for the COVID-19 patients with pre-existing ILD.Recommendation 3: ILD is an independent risk factor for severe/critical COVID-19. We recommend antiviral treatment for COVID-19 patients with pre-existing ILD as early as possible after symptoms onset, ideally within 5 days.Recommendation 4: We recommend that the use of systemic corticosteroids in COVID-19 patients with pre-existing ILD who had no indications for corticosteroids therapy should follow the guidelines of COVID-19 for the general population. Those with pre-existing ILD who need to start or are already on systemic corticosteroids are recommended to start or continue corticosteroids if they develop COVID-19. The dose adjustment is based on the severity of COVID-19 with pre-existing ILD: For the patients with severe/critical COVID-19 with pre-existing ILD but no AE-ILD, the use of corticosteroids should follow the guidelines of COVID-19 in the general population; the patients with AE-ILD are recommended to follow the use of corticosteroids in AE-ILD.Recommendation 5: There is no evidence available for the use of interleukin-6 receptor blockers in COVID-19 patients with pre-existing ILD. Recommendations regarding interleukin-6 receptor blockers in COVID-19 patients with pre-existing ILD may follow the guideline of COVID-19 in the general population.Recommendation 6: There is no evidence to support the use of Janus kinase inhibitors in COVID-19 patients with pre-existing ILD. The use of Janus kinase inhibitors in COVID-19 patients with pre-existing ILD is recommended to follow the guideline of COVID-19 in the general population.Recommendation 7: For patients who have not started immunosuppressants/biological agents for pre-existing ILD at the time of COVID-19, delayed initiation of immunosuppressants/biological agents is recommended, if the risk of ILD progression in the short term is low. For patients who are already on immunosuppressants/biological agents, a multidisciplinary discussion with rheumatologists is recommended to weigh the benefits and risks of discontinuing immunosuppressants/biological agents. It is recommended to discontinue immunosuppressants/biological agents for pre-existing ILD in acute phase of COVID-19 unless short-term discontinuation affects control of underlying ILD or connective tissue disease.Recommendation 8: It is recommended that the COVID-19 patients with pre-existing ILD who are on anti-fibrotic medication should continue to take anti-fibrotic medication. For COVID-19 patients with newly diagnosed fibrotic ILD who need to start anti-fibrotic therapy, it is recommended to start anti-fibrotic treatment as early as possible.Recommendation 9: It is recommended to investigate and monitor co-infections and secondary infections in COVID-19 patients with pre-existing ILD, and to promptly prevent and treat co-infections and secondary infections such as bacteria, fungi, Pneumocystis jirovecii, and cytomegalovirus.Recommendation 10: Anticoagulation therapy for the COVID-19 patients with pre-existing ILD is recommended to be used in accordance with guideline of COVID-19 in general population.Recommendation 11: For COVID-19 patients with pre-existing ILD, we recommend follow-up at 4 weeks after recovery (non-hospitalized patients) or 4 weeks after discharge (hospitalized patients), and then the routine monitoring frequency for ILD once stable, i.e. every 3 to 6 months. Pulmonary function testing is a routine investigation. Chest HRCT is suggested when clinically indicated. Arterial blood gas analysis, echocardiography, CT pulmonary angiography, and blood examinations can be selected when necessary.Recommendation 12: Severe/critical COVID-19 survivors are the main target population for rehabilitation intervention. Rehabilitation therapy should be administered individualized.Recommendation 13: Healthcare providers should fully inform patients with pre-existing ILD about the benefits and risks of vaccination, and involve patients in a shared decision-making process to discuss whether or not to receive a COVID-19 vaccine.Recommendation 14: For PC-ILD patients with persistent or progressive respiratory symptoms, persistent interstitial lung abnormalities and lung function impairment following acute COVID-19 pneumonia, may be treated with glucocorticoids after exclusion of other causes such as infection.Recommendation 15: For PC-ILD patients who have recovered from severe/critical COVID-19, anti-fibrotic medications may be administered after discussing disease-and treatment-related factors with patients. The optimal timing and duration of anti-fibrotic treatment are still uncertain. We conditionally recommend against anti-fibrotic medications in patients who have recovered from mild or moderate COVID-19. This recommendation does not apply to patients with pre-existing fibrotic ILD.
新型冠状病毒感染（coronavirus disease 2019，COVID-19）在世界范围内流行，然而目前对于如何管理间质性肺疾病（interstitial lung disease，ILD）合并COVID-19患者的临床认识非常有限。另一方面，急性COVID-19后发生的ILD（post-acute covid-19 ILD，PC-ILD）也很常见，如何规范管理也是临床面临的问题。为此，中国研究型医院学会呼吸分会邀请国内ILD领域专家组成共识编写组，充分收集临床意见，基于临床收集问题，组织专家讨论，最终确定纳入了22个问题，主要包括ILD合并COVID-19患者临床特征、重症/死亡风险和风险因素、治疗管理、PC-ILD临床特征、风险因素和治疗等方面。基于国内外指南、临床研究数据等证据，经过多次讨论和投票表决，形成15条推荐意见，共同制定了《新型冠状病毒感染疫情下间质性肺疾病患者临床管理中国专家共识》，旨在提升对ILD合并COVID-19以及PC-ILD的认识，为临床决策提供依据，提高临床救治水平。推荐意见1：新冠肺炎与急性/亚急性起病的ILD建议从暴露史、症状体征、肺高分辨率CT（HRCT）特征、实验室检查5个方面鉴别。推荐意见2：参考新型冠状病毒感染诊疗方案（试行第十版），对ILD合并COVID-19疾病严重程度分级及管理。推荐意见3：ILD是COVID-19重症/危重症独立危险因素，ILD合并COVID-19患者应尽早进行抗病毒治疗，最佳使用时机为出现症状5 d以内。推荐意见4：基础ILD无激素治疗指征者急性COVID-19时激素使用遵照COVID-19激素使用原则。基础ILD需开始或已使用激素者出现急性COVID-19时可继续使用激素，剂量调整依据基础ILD和COVID-19病情需要：重型/危重型ILD合并COVID-19但不符合SARS-Cov-2 触发AE-ILD者激素使用遵照重型/危重型COVID-19使用原则；符合AE-ILD者按AE-ILD处理。推荐意见5：IL-6抑制剂在COVID-19合并ILD人群中的使用尚无针对此类人群的临床研究证据，建议参照一般COVID-19患者使用原则。推荐意见6：JAK抑制剂在COVID-19合并ILD患者中的使用也无针对此类人群的临床研究证据，建议参照一般COVID-19患者使用原则。推荐意见7：对于出现COVID-19时尚未使用免疫抑制剂/生物制剂的ILD患者，若短期ILD进展的可能性低，可适当延迟启动免疫抑制剂/生物制剂治疗至COVID-19急性期后。对于已使用免疫抑制剂/生物制剂患者，建议采取多学科讨论方式，与风湿免疫科医生共同讨论，根据个体评估结果，权衡免疫抑制剂继续使用的获益和风险，COVID-19急性期可暂停免疫抑制剂，除非短期停用影响基础ILD或结缔组织疾病病情控制。推荐意见8：基础ILD使用抗纤维化药物者出现COVID-19时应继续使用抗纤维化药物，对于新诊断的纤维化性ILD需要使用抗纤维化药物的患者，建议及早启动抗纤维化治疗。推荐意见9：ILD合并COVID-19患者应积极进行病原学检查监测合并和（或）继发感染，及时应用抗感染药物预防或治疗细菌、真菌、耶氏肺孢子菌、巨细胞病毒等感染。推荐意见10：ILD合并COVID-19患者抗凝治疗建议按照一般患者原则使用。推荐意见11：在起病后（未住院患者）或出院后（住院患者）4周时随访。若病情稳定，可参照普通ILD患者诊疗常规，每3~6个月随访1次。胸部HRCT和肺功能是常规随访项目。动脉血气分析、心脏超声、CT肺动脉造影、血液学检查根据患者病情需要酌情选择。推荐意见12：胸部CT明显异常、肺功能受损严重的重型/危重型COVID-19患者，是康复干预的主要目标人群。康复治疗应遵循个体化治疗原则。推荐意见13：医务工作者和疫苗接种人员应让患者充分知情接种疫苗的获益及风险，并与患者共同讨论决策是否接种疫苗。推荐意见14：对于急性COVID-19后仍有持续或进展的呼吸道症状，肺间质病变范围仍较大者，在排除感染等其他病因后可加用激素治疗。推荐意见15：重症/危重症COVID-19后PC-ILD患者可加用抗纤维化药物治疗，但需要基于纤维样病变的范围、药物副作用、超适应症用药等问题，与患者协商后个体化决定。用药最佳时机、疗程尚不确定。对于轻、中型COVID-19后患者不倾向加用抗肺纤维化药物，可随访监测，基础存在纤维化性ILD患者除外。.

The UK National Centre for the Replacement, Refinement, and Reduction of Animals in Research (NC3Rs) is reviewing World Health Organization (WHO) manuals, guidelines and recommendations for vaccines and biotherapeutics to identify the extent to which animal-based testing methods are described. The aim is to recommend where updates to these documents can lead to an increased and more harmonised adoption of 3Rs principles (i.e. Replacement, Reduction and Refinement of animal tests) in the quality control and batch release testing requirements for vaccines and biotherapeutics. Improved adoption of 3Rs principles and non-animal testing strategies will help to reduce the delays and costs associated with product release testing. Developing recommendations that are widely applicable by both the manufacturers and national regulatory authorities for vaccines and biological therapeutics globally requires a detailed understanding of how different organisations view the opportunities and barriers to better integration of the 3Rs. To facilitate this, we developed and distributed a survey aimed at individuals who work for national regulatory authorities (NRAs) and/or national control laboratories (NCLs). In this paper, we present the key findings from this survey and how these will help inform the recommendations for wider integration of 3Rs approaches by WHO in their guidance documents applicable to the quality control and batch release testing of vaccines and biotherapeutics.

Psoriasis is nowadays regarded as a multifactorial, inflammatory, immune-mediated systemic condition with predominant involvement of the skin. It starts in about one third of cases in childhood and adolescence and is often accompanied by marked impairment of the quality of life of sufferers and their parents. Aside from genetic disposition, trigger factors such as streptococcal infections are notably involved in manifestation and in exacerbations. The harmful role of comorbidities even in the young, particularly of obesity, has been well documented. Treatment options have considerably improved following the approval of five biologic agents in childhood but are still insufficiently used. The present article gives a short overview of current knowledge and the recommendations of the updated German guideline. Besides frequent types, unusual presentations such as pustular psoriasis, psoriasis dermatitis, and paradoxical psoriasis induced by tumor necrosis factor alpha (TNF-α) inhibitors are addressed.
UNASSIGNED: Die Psoriasis wird heute als multifaktorielle, entzündliche, immunmediierte Systemerkrankung mit vorrangiger Manifestation am Hautorgan aufgefasst. In etwa einem Drittel der Fälle beginnt sie bereits im Kindes- und Jugendalter und geht oft mit einer deutlichen Beeinträchtigung der Lebensqualität Betroffener und ihrer Eltern einher. Neben der genetischen Disposition sind Triggerfaktoren wie Streptokokkeninfektionen maßgeblich an der Manifestation und an Exazerbationen beteiligt. Auch die bereits in dieser Altersgruppe nachteilige Rolle von Komorbiditäten, allen voran die Adipositas, wurde inzwischen gut belegt. Die Behandlungsmöglichkeiten haben sich durch die Zulassung von nunmehr 5 Biologika im Kindesalter erheblich verbessert, werden aber noch unzureichend genutzt. Der vorliegende Beitrag gibt einen kurzen Überblick über den heutigen Wissensstand und die Empfehlungen der aktualisierten deutschen Leitlinie. Neben den häufigen Typen werden auch ungewöhnlichere Erscheinungsformen wie die pustulöse, die ekzematisierte und die durch TNF(Tumornekrosefaktor)-α-Inhibitoren induzierte „paradoxe“ Psoriasis thematisiert.

With the current study, we aimed at evaluating the quantiferon test results of psoriasis patients treated with biological agents.
Between April 2019 and June 2021, medical records of patients with psoriasis who were evaluated for latent tuberculosis infection before the initiation of biological agent treatment were reviewed retrospectively.
This study included 132 patients, 50 (37.9%) female and 82 (62.1%) male. The mean disease duration was 16.42±10.99 years (range: 1-49 years). None of the patients had a previous history of tuberculosis. Quantiferon test was negative in 109 (82.6%) patients and positive in 23 (17.4%) patients. Patients with positive quantiferon test results were older than those who had negative quantiferon test results; the mean ages were 50.21±10.79 and 42.98±11.81 years, respectively (p=0.006).
Within this study, 17.4% of patients with psoriasis had positive quantiferon test results. We suggest that quantiferon test should be performed in all patients with psoriasis especially in the elderly for latent tuberculosis screening before the initiation of biological agent treatment. Moreover, we suggest that psoriasis treatment guidelines with biological agents should include detailed information on the necessity of chest radiograph, choosing tuberculin skin test or interferon gamma release assays such as quantiferon and T-spot test. In addition, controversies on the requirement of screening for latent tuberculosis and prophylactic tuberculosis treatment before the initiation of novel biological agents such as IL-17 and IL-23 inhibitors should be clarified. An international consensus on the duration of latent tuberculosis treatment and the interval between tuberculosis prophylaxis and the initiation of biological agents should be achieved.

OBJECTIVE: The management of biological agents during pregnancy poses challenges as maternal and infant safety must be addressed. This study aims to compare the recommendations of existing guidelines on managing the use of biologics during pregnancy, lactation for patients with inflammatory bowel disease, and the influence on neonatal vaccination.
METHODS: The PubMed, EMBASE, China National Knowledge Infrastructure, Wanfang database, China Science and Technology Journal Database and China Biomedical Database were systematically searched from the inception date to 11 May 2022, to screen all relevant guidelines. Quality assessment was performed using the guideline methodology reporting tool AGREE II.
CONCLUSIONS: Fourteen guidelines and consensus statements with detailed recommendations were included. All guidance documents cover management comments during pregnancy, and most consider that biologics can be given safely during pregnancy but require suspension at the right time to protect the foetus. However, the roles of vedolizumab and ustekinumab are disputed. Five documents guide lactation and the use of most biologics during lactation is safe, but no guidelines recommend vedolizumab. Six papers provide recommendations for newborns\' vaccination, suggesting a delay in infants\' live vaccination schedule if their mothers are treated with biologics.
CONCLUSIONS: Our study concluded that future guidelines could consider incorporating newer, more robust evidence to update recommendations. The development of future guidelines needs to consider the involvement of multidisciplinary experts, adequately report on the evidence retrieval process, and provide strategies for implementation. Besides, more research is needed to explore the use of biologics during pregnancy and lactation in patients with inflammatory bowel disease.

The UK National Centre for the Replacement, Refinement, and Reduction of Animals in Research (NC3Rs) has been tasked by the World Health Organization (WHO) to review the extent to which animal-based testing methods are described in their manuals, guidelines and recommendations for vaccines and biotherapeutics. The aim is to identify and recommend where updates to these documents can lead to an increased and more harmonised adoption of 3Rs principles (i.e. Replacement, Reduction and Refinement of animal tests) in the quality control and batch release testing requirements for vaccines and biotherapeutics. Developing recommendations that are widely applicable by both the manufacturers and national regulatory authorities for vaccines and biologicals globally requires a detailed understanding of how different organisations view the opportunities and barriers to better integration of the 3Rs. To facilitate this, we developed and distributed a survey aimed at vaccine and biotherapeutics manufacturers in July 2021. In this paper, we present the key findings from this survey and how these will help inform the recommendations for wider integration of 3Rs approaches by WHO in their guidance documents applicable to the quality control and batch testing of vaccines and biotherapeutics.

Psoriasis is a common chronic skin disease characterized by a worldwide distribution and a natural tendency towards progression. According to the many clinical forms, the extension of the disease and the many comorbidities, almost the 20% of the patients require a systemic treatment. Biologics have greatly changed the ongoing of psoriasis and the quality of life of psoriasis patients. After the anti-TNF-alpha, which were the first biologics in use for psoriasis, the improvement in knowledge of the pathogenetic mechanisms underlying the disease has led to the development of a series of more specific therapies for psoriasis. This \"second generation\" of biologics includes the interleukin (IL)-12/23 inhibitor ustekinumab, IL-17 inhibitors (secukinumab and ixekizumab), the IL-17 receptor A (IL-17RA) antagonist brodalumab, and the IL-23 inhibitors guselkumab, risankizumab and tildrakizumab. This study represents an update of the Tuscany consensus focused on the use of new drugs, such as anti-IL-17 and anti-IL-23 in moderate-to-severe psoriasis and their correct place in therapy according to specific clinical requests and in full respect of the current financial restrictions.

OBJECTIVE: Since its inception, the Psoriasis Group (GPs) of the Spanish Academy of Dermatology and Venereology (AEDV) has worked to continuously update recommendations for the treatment of psoriasis based on the best available evidence and incorporating proposals arising from and aimed at clinical practice. An updated GPs consensus document on the treatment of moderate to severe psoriasis was needed because of changes in the treatment paradigm and the approval in recent years of a large number of new biologic agents.
METHODS: The consensus document was developed using the nominal group technique complemented by a scoping review. First, a designated coordinator selected a group of GPs members for the panel based on their experience and knowledge of psoriasis. The coordinator defined the objectives and key points for the document and, with the help of a documentalist, conducted a scoping review of articles in Medline, Embase, and the Cochrane Library up to January 2021. The review included systematic reviews and meta-analyses as well as clinical trials not included in those studies and high-quality real-world studies. National and international clinical practice guidelines and consensus documents on the management of moderate to severe psoriasis were also reviewed. The coordinator then drew up a set of proposed recommendations, which were discussed and modified in a nominal group meeting. After several review processes, including external review by other GPs members, the final document was drafted.
RESULTS: The present guidelines include updated recommendations on assessing the severity of psoriasis and criteria for the indication of systemic treatment. They also include general principles for the treatment of patients with moderate to severe psoriasis and define treatment goals for these patients as well as criteria for the indication and selection of initial and subsequent therapies Practical issues, such as treatment failure and maintenance of response, are also addressed.

Precision medicine approaches are receiving increased attention in dermatology, including inflammatory skin diseases. In psoriasis, a precision medicine treatment paradigm could temper the rapid increase in pharmacy costs that have resulted from a tremendous expansion in the number of available biologic drug options. However, without a clear and agreed upon proof of clinical utility in a real-world setting, costly new pharmacotherapies are often burdened with barriers to coverage by payers and ultimately, routine patient care. This panel was assembled to discuss the evidence threshold required to demonstrate the clinical utility of a precision medicine diagnostic that predicts the biologic therapeutic class for treating psoriasis patients. The panel reviewed clinical utility study designs and economic impact study designs aimed at delineating net savings and waste reduction. A psoriasis biologic precision medicine test could optimize pharmacotherapy management of psoriasis patients. The consensus opinion of this panel was that positive results from the study described here would prove the clinical utility of this precision medicine test. J Drugs Dermatol. 2022;21(6):630-636. doi:10.36849/JDD.6864.

OBJECTIVE: Since its inception, the Psoriasis Group (GPs) of the Spanish Academy of Dermatology and Venereology (AEDV) has worked to continuously update recommendations for the treatment of psoriasis based on the best available evidence and incorporating proposals arising from and aimed at clinical practice. An updated GPs consensus document on the treatment of moderate to severe psoriasis was needed because of changes in the treatment paradigm and the approval in recent years of a large number of new biologic agents.
METHODS: The consensus document was developed using the nominal group technique complemented by a scoping review. First, a designated coordinator selected a group of GPs members for the panel based on their experience and knowledge of psoriasis. The coordinator defined the objectives and key points for the document and, with the help of a documentalist, conducted a scoping review of articles in Medline, Embase, and the Cochrane Library up to January 2021. The review included systematic reviews and meta-analyses as well as clinical trials not included in those studies and high-quality real-world studies. National and international clinical practice guidelines and consensus documents on the management of moderate to severe psoriasis were also reviewed. The coordinator then drew up a set of proposed recommendations, which were discussed and modified in a nominal group meeting. After several review processes, including external review by other GPs members, the final document was drafted.
RESULTS: The present guidelines include updated recommendations on assessing the severity of psoriasis and criteria for the indication of systemic treatment. They also include general principles for the treatment of patients with moderate to severe psoriasis and define treatment goals for these patients as well as criteria for the indication and selection of initial and subsequent therapies Practical issues, such as treatment failure and maintenance of response, are also addressed.