[Effect and mechanism of aqueous extract of Strychni Semen on bone destruction in rats with type â ¡ collagen-induced rheumatoid arthritis].

To investigate the mechanism of action of aqueous extract of Strychni Semen(SA) on bone destruction in rats with type Ⅱ collagen-induced arthritis(CIA), the SD rats were randomly divided into normal group, model group, low, medium, and high dose(2.85, 5.70, and 11.40 mg·kg~(-1)) groups of SA, and methotrexate group. Except for the normal group, the CIA model was prepared for the other groups. After the second immunization, different doses of SA were given to the low, medium, and high dose groups of SA once a day, and the methotrexate group was given once every three days. 0.3% sodium hydroxymethylcellulose(CMC-Na) was given once a day to the normal and model groups for 28 d. The clinical score of arthritis was evaluated every three days. Micro computed tomography(Micro-CT) method was used to evaluate the degree of bone destruction. Histopathological changes in the joint tissue and the number of osteoclasts in CIA rats were evaluated by hematoxylin-eosin(HE) staining and tartrate-resistant acid phosphatase(TRAP) staining. The expression of interleukin-1ß(IL-1ß) in the joint tissue of rats was detected by immunohistochemistry. Western blot was used to detect key protein expression in mitogen-activated protein kinase(MAPK) and phosphatidylinositol 3-kinase/protein kinase B(PI3K/Akt) signaling pathways in the joint tissue of rats. The results showed that different doses of SA were able to improve the red and swollen inflammatory joint and joint deformity in CIA rats to varying degrees, reduce the clinical score, inhibit synovial inflammation, vascular opacification, cartilage erosion, and bone destruction, and reduce the number of TRAP-positive cells in bone tissue. Micro-CT results showed that the SA was able to increase bone mineral density, bone volume fraction, trabecular reduce, and trabecular number and reduce bone surface/bone volume and trabecular separation/spacing. Different doses of SA could down-regulate the protein expression of IL-1ß, p-JNK, p-ERK, p-p38, PI3K, and p-Akt to varying degrees. In conclusion, SA can improve disease severity, attenuate histopathological and imaging changes in joints, and have osteoprotective effects in CIA rats, and its mechanism of action may be related to the inhibition of the overactivation of MAPK and PI3K/Akt signaling pathways.

Risk factors associated with high-dose methotrexate induced toxicities.

INTRODUCTION: High-dose methotrexate (HDMTX) therapy poses challenges in various neoplasms due to individualized pharmacokinetics and associated adverse effects. Our purpose is to identify early risk factors associated with HDMTX-induced toxicities, paving the way for personalized treatment. AREAS COVERED: A systematic review of PubMed and Cochrane databases was conducted for articles from inception to July 2023. Eligible studies included reviews, clinical trials, and real-world analyses. Irrelevant studies were excluded, and manual searches and citation reviews were performed. Factors such as MTX exposure, drug interactions, demographics, serum albumin, urine pH, serum calcium, and genetic polymorphisms affecting MTX transport (e.g. SLCO1B1), intracellular folate metabolism (MTHFR), cell development (ARID5B), metabolic pathways (UGT1A1, PNPLA3), as well as epigenetics were identified. EXPERT OPINION: This comprehensive review aids researchers and clinicians in early identification of HDMTX toxicity risk factors. By understanding the multifaceted risk factors associated with hematologic malignancies, personalized treatment approaches can be tailored to optimize therapeutic outcomes.

Rheumatoid arthritis: prediction of future clinically-apparent disease, and prevention.

PURPOSE OF REVIEW: This review discusses updates in the prediction and prevention of future rheumatoid arthritis (RA). RECENT FINDINGS: In individuals with musculoskeletal symptoms and elevated antibodies to citrullinated proteins (ACPA) without clinical inflammatory arthritis (IA), a 'simple' score has a positive predictive value (PPV) of ∼28% for clinical IA/RA within 1 year, and a comprehensive score (including ultrasound) has a PPV of ∼71% for clinical RA within 5 years. Controlled clinical trials in individuals at-risk for future RA have been performed using corticosteroids, rituximab, atorvastatin, methotrexate, hydroxychloroquine and abatacept. Abatacept modestly reduced rates of incident clinical RA and imaging inflammation within the trials, rituximab delayed clinical IA, and methotrexate improved function, symptoms and imaging inflammation. Vitamin D with or without omega 3 fatty acids reduced incidence of autoimmune diseases, including RA. While not proven in controlled clinical trials, observational studies suggest exercise, weight loss and smoking cessation may reduce progression to clinical RA. SUMMARY: Prediction and prevention of RA is advancing although there are no currently approved interventions for prevention. Future studies should include deeper evaluation of the pathophysiology of RA development to improve prediction and identify key pathways to target in future clinical trials, as well as develop infrastructure to support prevention-related research.

An acute herb-drug interaction of Magnoliae Officinalis Cortex with methotrexate via inhibiting multidrug resistance-associated protein 2.

Magnoliae Officinalis Cortex (MOC), an herbal drug, contains polyphenolic lignans mainly magnolol (MN) and honokiol (HK). Methotrexate (MTX), a critical drug for cancers and autoimmune deseases, is a substrate of multidrug resistance-associated protein 2 (MRP2) and breast cancer resistance protein (BCRP). This study investigated the effect of coadministration of MOC on the pharmacokinetics of MTX and relevant mechanisms. Sprague-Dawley rats were orally administered MTX alone and with single dose (2.0 and 4.0 g/kg) and repeated seven doses of MOC (2.0 g/kg thrice daily for 2 days, the 7th dose given at 0.5 h before MTX). The serum concentrations of MTX were determined by a fluorescence polarization immunoassay. The results showed that a single dose of MOC at 2.0 g/kg significantly increased the AUC0-t and MRT of MTX by 352% and 308%, and a single dose at 4.0 g/kg significantly enhanced the AUC0-t and MRT by 362% and 291%, respectively. Likewise, repeated seven doses of MOC at 2.0 g/kg significantly increased the AUC0-t and MRT of MTX by 461% and 334%, respectively. Mechanism studies indicated that the function of MRP2 was significantly inhibited by MN, HK and the serum metabolites of MOC (MOCM), whereas BCRP was not inhibited by MOCM. In conclusion, coadministration of MOC markedly enhanced the systemic exposure and mean residence time of MTX through inhibiting the MRP2-mediated excretion of MTX.

Co-Delivery of Aceclofenac and Methotrexate Nanoparticles Presents an Effective Treatment for Rheumatoid Arthritis.

Background: Rheumatoid arthritis (RA) is a common acute inflammatory autoimmune connective tissue arthropathy. The genetic studies, tissue analyses, experimental animal models, and clinical investigations have confirmed that stromal tissue damage and pathology driven by RA mounts the chronic inflammation and dysregulated immune events. Methods: We developed methotrexate (MTX)-loaded lipid-polymer hybrid nanoparticles (MTX-LPHNPs) and aceclofenac (ACE)-loaded nanostructured lipid carriers (ACE-NLCs) for the efficient co-delivery of MTX and ACE via intravenous and transdermal routes, respectively. Bio-assays were performed using ex-vivo skin permeation and transport, macrophage model of inflammation (MMI) (LPS-stimulated THP-1 macrophages), Wistar rats with experimental RA (induction of arthritis with Complete Freund's adjuvant; CFA and BCG), and programmed death of RA affected cells. In addition, gene transcription profiling and serum estimation of inflammatory, signaling, and cell death markers were performed on the blood samples collected from patients with RA. Results: Higher permeation of ACE-NLCs/CE across skin layers confirming the greater "therapeutic index" of ACE. The systemic delivery of MTX-loaded LPHNPs via the parenteral (intravenous) route is shown to modulate the RA-induced inflammation and other immune events. The regulated immunological and signaling pathway(s) influence the immunological axis to program the death of inflamed cells in the MMI and the animals with the experimental RA. Our data suggested the CD40-mediated and Akt1 controlled cell death along with the inhibited autophagy in vitro. Moreover, the ex vivo gene transcription profiling in drug-treated PBMCs and serum analysis of immune/signalling markers confirmed the therapeutic role co-delivery of drug nanoparticles to treat RA. The animals with experimental RA receiving drug treatment were shown to regain the structure of paw bones and joints similar to the control and were comparable with the market formulations. Conclusion: Our findings confirmed the use of co-delivery of drug nanoformulations as the "combination drug regimen" to treat RA.

Statin-induced debilitating weakness and myopathy.

A large percentage of the US population is either receiving or should be considered for statin therapy. Whether through primary or secondary prevention for atherosclerotic disease, statins remain one of the mainstay options available to physicians. Myalgias are the most commonly reported side effects, though largely self-limited and subjective in nature. Here, we report a case of drug-related myonecrosis following long-term use of atorvastatin. Prompt recognition of the condition and initiation of treatment is paramount to control the disease's progression. While high-dose steroids are first line, quick escalation to methotrexate, IVIG or rituximab should be considered in refractory cases. This decision is guided by monitoring of serum markers such as CK and transaminases. The goal is quick normalisation of these enzymes, signalling cessation of underlying muscle necrosis. Patients may never regain full function and treatment can last months to years.

[Localized scleroderma]. / Lokalisierte Sklerodermie.

Localized scleroderma (LS), also called circumscribed scleroderma or morphea, comprises a heterogeneous group of diseases that can be classified into four subtypes: limited, linear, generalized, and mixed LS. All manifestations are primarily due to chronic progressive fibrosis of the skin or structures close to the skin. Involvement of internal organs or the transition to systemic sclerosis is excluded by definition. A distinction is made between forms that primarily affect the skin (up to the dermis) or that severely involve subcutaneous fat tissue, muscle fascia or muscles. A detailed examination is required for clinical diagnosis. In order to improve comparability of findings, photo documentation and the use of clinical scores should be carried out. For superficial subtypes the use of topical glucocorticosteroids, calcineurin inhibitors or phototherapy is initially recommended, whereas for severe forms with deep involvement or overall therapy refractoriness, the diagnosis should first be expanded and systemic therapy initiated at an early stage. Especially, in cross joint or extremity-dominant forms of linear LS or in cases with head and neck involvement, such as en coup de sabre, Parry-Romberg syndrome and other subtypes with a prominent musculoskeletal affection, an MRI examination should be arranged. Depending on location, an ophthalmological, neurological, orthodontic, rheumatological or orthopedic consultation may be necessary. For systemic therapy, methotrexate alone or in combination with systemic glucocorticosteroids as pulse therapy is recommended as first-line treatment.

TWEAK levels in psoriatic patients treated with narrowband ultraviolet B and methotrexate.

BACKGROUND: Psoriasis is an autoimmune disease which has an effect on the joints and skin. Tumor Necrosis Factor-Like Weak Inducer of Apoptosis (TWEAK) is a multi-functional cytokine which regulates the cellular processes and has been related to a variation of conditions. OBJECTIVES: To measure the level of serum TWEAK in psoriatic diseased persons and its relationship to the PASI score pre- and post-therapy with narrowband ultraviolet B phototherapy (NB-UVB) and methotrexate (MTX). METHODS: This randomized controlled trial was conducted on 40 patients and 20 healthy persons as controls. Patient Group was randomly subdivided to two groups. The 1st group consisted of 20 patients who received NB-UVB treatment. The 2nd group included 20 MTX-treated candidates. Blood samples were drawn from patients in order to detect serum TWEAK levels using ELISA. The research was registered on Clinical Trials Registration: RCT approval numbers: NCT0481191. RESULTS: The mean PASI score percent improvement after 12 weeks of treatment was higher in the MTX group (90%) than NB-UVB group (60%). The serum TWEAK level at baseline was 60.47 ± 12.6 pg/mL in NB-UVB group and 54.69 ± 21.7 pg/mL in MTX group which reduced to 24.93 ± 17.6 pg/mL and 32.13 ± 23.6 pg/mL, respectively (p < 0.001), after 12 weeks of treatment. There was a positive correlation between the serum levels of TWEAK and severity of PASI score (r = 0.399, p = 0.014). CONCLUSION: TWEAK grades in psoriasis are substantially higher than in controls. TWEAK levels were dramatically reduced during NB-UVB and MTX treatment. TWEAK may have a potential sign for psoriasis diagnosis and prognosis.

Selenium mitigates methotrexate-induced testicular injury: Insights from male NMRI mice model.

BACKGROUND AND AIM: Chemotherapy, particularly with methotrexate (MTX), often elicits testicular toxicity, leading to impaired spermatogenesis and hormone imbalances. This study aimed to investigate the potential protective effects of selenium (Se) against MTX-induced testicular injury. MATERIALS AND METHODS: Male mice were divided into control, MTX, Se, and MTX + Se groups. Histopathological examination involved the preparation of testicular tissue sections using the Johnsen's tubular biopsy score (JTBS) for spermatogenesis evaluation. Biochemical tests included the assessment of testosterone, malondialdehyde (MDA), luteinizing hormone (LH), and follicle-stimulating hormone (FSH) levels. Real-time quantitative polymerase chain reaction (RT-qPCR) was employed to analyze the expression of caspase 3 (casp3), tumor protein 53 (p53), B-cell lymphoma 2 (Bcl2), and Bcl2-associated X protein (Bax) genes. Statistical analysis was performed using ANOVA and Tukey's tests (p < .05). RESULTS: Histopathological analysis revealed significant testicular damage in the MTX group, with decreased spermatogenesis and Leydig cell count, while Se administration mitigated these effects, preserving the structural integrity of the reproductive epithelium. Biochemical analysis demonstrated that MTX led to elevated malondialdehyde (MDA) levels and reduced testosterone, LH, and FSH levels, suggesting oxidative stress and Leydig cell dysfunction. Gene expression analysis indicated that MTX upregulated proapoptotic genes (casp3, p53, and bax) while downregulating the antiapoptotic Bcl2 gene. In contrast, Se treatment reversed these trends, highlighting its potential antiapoptotic properties. CONCLUSION: Our findings underscore the potential of Se as a therapeutic agent to mitigate the reproductive toxicity associated with MTX-induced testicular injury. Se exerts protective effects by regulating oxidative stress, preserving hormone balance, and modulating apoptotic pathways. These results suggest that Se supplementation could be a promising strategy to alleviate chemotherapy-induced testicular damage and preserve male fertility.

[Radiation-induced morphea-an overview]. / Postradiogene Morphea ­ eine Übersicht.

BACKGROUND: Radiation-induced morphea is a fibro-inflammatory remodelling process of the subcutaneous connective tissue caused by ionising radiation, most commonly in the context of breast cancer treatment. The underlying pathomechanisms and putative risk factors are unknown. Therefore, misdiagnosis and inappropriate treatment pose a significant problem in the care of those patients. OBJECTIVES: The aim of the study was to provide an overview as well as guidance for the diagnosis and treatment of radiation-induced morphea based on current case reports and review articles. RESULTS AND CONCLUSIONS: Radiation-induced morphea is a rare condition that represents an interdisciplinary challenge for (gynaecological) oncology, radiotherapy and dermatology. Frequent misdiagnoses include infection (erysipelas), cancer recurrence or radiation dermatitis. Early histological diagnosis and the initiation of anti-inflammatory therapy using topical glucocorticoids or calcineurin inhibitors in combination with phototherapy and/or methotrexate are the most relevant success factors for an adequate clinical response.

Efficacy and safety of the modified Zhiwang decoction combined with methotrexate in early rheumatoid arthritis: study protocol for a randomised controlled trial.

INTRODUCTION: Rheumatoid arthritis (RA) is a progressive inflammatory autoimmune disease characterised by chronic systemic inflammation, which can cause swelling, stiffening and destruction of articular cartilage and bone. Early diagnosis and treatment of RA can improve outcomes and slow the progression of joint damage. Preliminary exploratory research had hinted an expected effect of modified Zhiwang decoction (MZWD) in treating early RA. However, few randomised clinical trials have evaluated the effectiveness of MZWD in early RA. Therefore, a parallel-group randomised controlled trial was designed to evaluate the efficacy and safety of MZWD combined with methotrexate (MTX) on early RA. METHODS AND ANALYSIS: This is a prospective, parallel-group, single-centre randomised controlled clinical study. A total of 150 patients will be randomly assigned to either the treatment (n=75) or control group (n=75). The treatment group will receive MZWD and MTX, and the control group will receive MTX for 12 weeks. The primary outcome of this study is Disease Activity Score-28, and the secondary outcomes are Fatigue Scale-14, Visual Analogue Scale pain scores and traditional Chinese medicine symptom scores. Safety outcomes, including adverse events and results of ECG and laboratory tests, will be monitored. ETHICS AND DISSEMINATION: Ethics approval was obtained from the Clinical Research Ethics Committee of the China-Japan Friendship Hospital (no. 2022-KY-124) on 8 July 2022. The findings will be disseminated in peer-reviewed publications. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Registry (NCT05508815).

Exploring the potential molecular mechanism of Gualou Guizhi decoction in the treatment of rheumatoid arthritis based on network pharmacology and molecular docking.

BACKGROUND: Traditional Chinese medicine (TCM) has been used in China for a long time and is gradually gaining more and more recognition worldwide. Gualou Guizhi Decoction (GGD) has long been used as a folk medicine for the treatment of rheumatic diseases, but its bioactive components and therapeutic mechanisms are still unclear. METHODS: An integrated approach using network pharmacology and molecular docking and using methotrexate as a positive control drug. RESULTS: We obtained 157 active ingredients of GGD, 7542 RA disease targets and 49 intersecting targets. GO and KEGG enrichment analysis revealed that their functions were mainly related to cytokine active metal ion binding, enzyme binding and DNA binding, and enriched in TNF signaling pathway, T cell receptor signaling pathway, Toll-like receptor signaling pathway, RA pathway and other signaling pathways that are closely related to RA. The molecular docking results show that the effector components of GGD bind better to the core targets of RA, and some are even better than methotrexate. CONCLUSION: The therapeutic effect of GGD for RA is achieved by affecting the core targets such as VEGFA, IL-1ß, IL6, CXCL8, CCL2, and JUN, which together interfere with the tumor necrosis factor signaling pathway and RA pathway to treat RA. The above study provides new ideas for further exploration of this classic formula in the future.

Delayed low-dose methotrexate excretion in a rheumatoid arthritis patient: A case report and literature review.

RATIONALE: Low-dose methotrexate has a relatively good safety profile. However, in cases where patients with multiple risk factors, a delayed excretion has been observed, resulting in the occurrence of severe adverse reactions. It is necessary to supervise and intervene throughout the entire process of treating patients with multiple risk factors for methotrexate, and to strengthen the rational application of methotrexate. PATIENT CONCERNS AND DIAGNOSES: A 66-year-old male patient was admitted to our hospital with rheumatoid arthritis and underlying conditions such as chronic obstructive pulmonary disease (COPD). This patient received treatment with low-dose MTX (10 mg/week) and experienced adverse reactions including anemia. He was diagnosed with methotrexate-induced bone marrow suppression. INTERVENTIONS AND OUTCOMES: The therapeutic drug monitoring revealed that the serum drug concentration of methotrexate was at a critical level and the patient was rescue with calcium folinate and other adjuvant therapy such as transfusions of red blood cells, plasma, platelets, oral Yixuesheng tablets and Leucogen tablets. We conducted a 1-month follow-up, and there was no recurrence of bone marrow suppression and anemia. LESSONS: To ensure rational administration of methotrexate, it is important to fully evaluate the clinical manifestations and physical condition of patients and regularly detecting the serum drug concentration of methotrexate when patients with multiple risk factors, Otherwise, even low-dose methotrexate administration may cause delayed excretion, resulting in severe adverse reactions.

Immunosuppressive and immunomodulating therapy for atopic dermatitis in pregnancy: an appraisal of the literature.

Atopic dermatitis (AD) is the most common dermatological diagnosis during pregnancy. Treatment of AD during pregnancy can be challenging, due to the unpredictable course and the fact that the therapy needs to be safe for both the mother and the fetus. Here we present an up-to-date appraisal of the literature on the treatment options available for AD in patients planning pregnancy, during pregnancy, and during breastfeeding. All patients with AD are recommended to supplement any medical treatment with daily applications of emollients. The first step in the medical treatment for AD during pregnancy are topical corticosteroids, and/or topical tacrolimus. If required, UV-light therapy can also be considered. Treatment with systemic therapy during pregnancy should always rely on a careful risk-benefit assessment and be based on shared-decision making between the treating physician and patient. The first-line systemic treatment option is cyclosporine A, whereas azathioprine may be considered in patients already receiving this treatment prior to pregnancy. Systemic glucocorticoids may also be used. Treatment with systemic JAK inhibitors is not recommended, whereas treatment with mycophenolate mofetil and methotrexate is contraindicated. Targeted therapy with dupilumab is not generally recommended, due to lack of experience in human pregnancies, yet some case-reports on their use are emerging. These recommendations are based on the authors appraisal of existing literature and the current recommendation from the European Task Force on Atopic Dermatitis. It is always the responsibility of the treating physician to stay updated on the newest guidelines and literature when treating patients with AD during pregnancy.

Methotrexate and electrostimulation cooperate to alleviate the relapse of psoriasiform skin inflammation by suppressing memory T cells.

Methotrexate (MTX) is an immunosuppressant used to treat autoimmune diseases, including psoriasis. However, like other immunosuppressants, MTX alone does not prevent their recurrence. Electrostimulation (ES) has been utilized to treat some inflammatory disorders without any major side-effect. But it remains unknown if ES alone, or together with MTX, ameliorates autoimmune disease relapse: a sticky medical problem. In particular, the mechanisms underlying ES action remain unclear. The objective of this study was to determine an impact of ES and/or MTX on psoriasis relapse and their potential cooperation. We found that regional ES, but not MTX, ameliorated psoriasiform skin inflammation recurrence. Interestingly, treatment with both MTX and ES further prevented psoriasis recurrence compared to ES alone. Moreover, ES downregulated potassium channel Kv1.3 on T-cells and reduced CD4+/CD8+ effector memory (TEM) and CD8+ skin-resident memory T (TRM) cells, while ES plus MTX further decreased CD8+ TEM/TRM cells compared to ES alone. However, ES failed to further attenuate psoriasis recurrence or suppress T cell memory in Kv1.3-deficient mice, whereas lack of Kv1.3 itself ameliorated psoriasis relapse by shrinking T cell memory pool. Importantly, ES moderately inhibited T-cell proliferation in vitro. ES also reduced human CD8+ TRM cells and attenuated human skin lesions in humanized mice grafted with lesional skin from patients with recurrent psoriasis, with an enhanced efficacy in mice treated with both ES and MTX. Thus, ES and MTX cooperated to prevent psoriasis relapse by reducing T-cell memory via targeting potassium channel Kv1.3. Our studies may be implicated for treating human psoriasis.

Magnetic nanocomposite through coating mannose-functionalized metal-organic framework with biopolymeric pectin hydrogel beads: A potential targeted anticancer oral delivery system.

This study designed magnetic nanocomposite hydrogel beads for a potential targeted anticancer oral delivery system. To end this, nanohybrids of Fe3O4/MIL-88(Fe) (FM) were synthesized through in-situ method by the treatment of terephthalic acid (TPA) and (Fe(NO3)3·9H2O) in the presence of Fe3O4 nanoparticles. They were then modified with mannose sugar as an anticancer receptor to achieve a targeted drug delivery system. After loading methotrexate (MTX), they were coated with pH-sensitive pectin hydrogel beads in the presence of a calcium chloride crosslinker for possible transferring the nanohybrids to the intestine through the acidic environment of the digestive system. The results of different analysis techniques showed that the materials were properly synthesized, coated, and loaded. The designed magnetic nanocomposite hydrogel beads showed pH-sensitive swelling and drug release rate, protecting MTX from the acidic environment of the stomach. MTT test revealed a good cytotoxicity toward colon cancer HT29 cell lines. Remarkably, the functionalization of MTX-loaded FM nanohybrids with mannose (MTX-MFM) enhanced their anticancer properties up to about 20 %. The results recommended that the prepared novel magnetic nanocomposite hydrogel beads have a good potential to be used as a targeted anticancer oral delivery system.

Guidelines of care for the management of atopic dermatitis in adults with phototherapy and systemic therapies.

BACKGROUND: For people with atopic dermatitis (AD) refractory to topical therapies, treatment with phototherapy and systemic therapies can be considered. Multiple biologic therapies and Janus kinase (JAK)inhibitors have been approved since 2014 to treat AD. These guidelines update the 2014 recommendations for management of AD with phototherapy and systemic therapies. OBJECTIVE: To provide evidence-based recommendations on the use of phototherapy and systemic therapies for AD in adults. METHODS: A multidisciplinary workgroup conducted a systematic review and applied the GRADE approach for assessing the certainty of evidence and formulating and grading recommendations. RESULTS: The workgroup developed 11 recommendations on the management of AD in adults with phototherapy and systemic agents, including biologics, oral JAK inhibitors, and other immunomodulatory medications. LIMITATIONS: Most randomized controlled trials of phototherapy and systemic therapies for AD are of short duration with subsequent extension studies, limiting comparative long-term efficacy and safety conclusions. CONCLUSIONS: We make strong recommendations for the use of dupilumab, tralokinumab, abrocitinib, baricitinib, and upadacitinib. We make conditional recommendations in favor of using phototherapy, azathioprine, cyclosporine, methotrexate, and mycophenolate, and against the use of systemic corticosteroids.

Executive summary: Guidelines of care for the management of atopic dermatitis in adults with phototherapy and systemic therapies.

BACKGROUND: The summarized guidelines update the 2014 recommendations for the management of AD with phototherapy and systemic therapies. METHODS: A multidisciplinary workgroup conducted a systematic review and applied the GRADE approach for assessing the certainty of the evidence and formulating and grading recommendations. RESULTS: The workgroup developed 11 recommendations on the management of AD in adults with phototherapy and systemic therapies, including biologics, oral Janus Kinase inhibitors, and other immunomodulatory medications. CONCLUSIONS: The evidence supported strong recommendations for the use of dupilumab, tralokinumab, abrocitinib, baricitinib, and upadacitinib and conditional recommendations in favor of using phototherapy, azathioprine, cyclosporine, methotrexate, and mycophenolate, and against the use of systemic corticosteroids.