In the current issue of JEADV, Fournier et al.1 describe dramatic and rapid recovery of children with severe juvenile dermatomyositis (JDM) treated with the interferon-beta (IFNβ) inhibitor dazukibart. A 15-year-old boy and 12-year-old girl (Patient 2) had over 5 years of persistent skin ulcerations and muscle weakness refractory to even third-line therapies, including systemic corticosteroids, methotrexate, intravenous immunoglobulin (IVIG), plasma exchange (PE) and Janus kinase inhibitors (JAKi). Patient 2 was unable to walk or sit up from bed and was receiving weekly PE and morphine. Under a compassionate access programme allowing for use of dazukibart in patients with serious or life-threatening disease, both patients received a single intravenous (IV) dose. As early as 4 weeks, both patients experienced dramatic muscle and skin improvement. Skin disease activity resolved and ulcerations healed. Patient 2 was walking within 4 weeks of the single dose and discontinued PE and morphine. Continued dazukibart monthly IV therapy resulted in continued improvement, including regression of calcinosis in one patient. No adverse side effects occurred. These children's responses are similar to the life-saving effect of dazukibart in another recent report of JDM compassionate access use.2 A 9-year-old girl with deep skin ulcers, interstitial lung disease and profound muscle weakness unable to lift her head off the bed, sit or walk despite 8 months of aggressive therapies developed extensive JDM-associated oesophageal, gastric and duodenal ulcers, resulting in a life-threatening duodenal perforation requiring intensive care unit (ICU) admission. Aggressive therapies including IVIG, subcutaneous methotrexate, mycophenolate mofetil and high dose cyclophosphamide (500 mg/m2 × 2) failed to achieve response. Emergency compassionate access use of a single IV dose of dazukibart resulted in dramatic improvement in skin, lung, muscle and gastrointestinal disease. By 4 weeks after a single dazukibart dose, skin ulcers had ceased to form and were healing, she was able to walk independently without assistive devices and returned to a full oral diet. Skin ulcers completely healed after a second dose, and at 14 months of continued therapy every 4–6 weeks, there had been no relapse of clinical skin, lung, muscle or gastrointestinal disease. No treatment-associated adverse events occurred. An additional publication describes compassionate access emergency use of dazukibart in an adult patient with MDA5 DM-associated rapidly progressive interstitial lung disease (RP-ILD), a condition with mortality approaching 80% in the first 3 months, whose skin and pulmonary function responded rapidly to dazukibart in an ICU setting.3 These compassionate access and emergency use dazukibart experiences in 3 children and 1 adult supplement the phase 2 placebo-controlled efficacy data demonstrating rapid and deep responses in a trial of 75 adult patients with dermatomyositis.4, 5 These compassionate use patients with life-threatening or severe disease who were ineligible for dazukibart clinical trials demonstrate the potential of dazukibart for transformative efficacy in patients with the most severe forms of DM, including those with RP-ILD, severe muscle disease resulting in disability, ulcerative skin disease and gastrointestinal involvement resulting in perforation. Notably, the pathophysiology of DM is mediated by IFNβ specifically.6, 7 Accordingly, as found by Fournier et al., the most targeted therapy towards IFNβ, dazukibart, was highly effective after multiple therapeutic failures. In personal experience (RAV), dazukibart has shown exceptional efficacy in treating severe and recalcitrant DM, with some patients entering long-term disease remission after treatment. Dr. Greenberg is an inventor of intellectual property related to dazukibart, assigned to and managed by Brigham and Women's Hospital, and licensed to Pfizer. Dr. Vleugels is an investigator for the Phase 3 dazukibart study. Data sharing is not applicable to this article as no datasets were generated or analysed during the current study.

Weber-Christian disease (WCD) is a rare idiopathic lobular panniculitis. Its diagnosis is challenging due to its ability to mimic infections and malignancies, often leading to unnecessary surgical interventions. A 35-year-old man presented with recurrent fever and painful subcutaneous nodules in 2017. For a period of 14 months, he underwent various interventions for suspected conditions, including empyema (thoracic drainage), spinal abscess (laminectomy), and infected renal cysts (nephrectomy). In March 2018, the diagnosis was confirmed by a skin biopsy, which revealed lobular panniculitis with foamy macrophages. The patient was successfully treated with subcutaneous methotrexate (10 mg/week) and oral methylprednisolone (4-8 mg/day). The patient has remained in clinical remission for approximately 1 year following the last disease flare in March 2022. Weber-Christian disease may present as recurrent surgical emergencies. Early deep tissue biopsy, routine histopathological examination of surgical specimens, and multidisciplinary evaluation are essential to avoid diagnostic delays. At the last follow-up (July 2023), the patient remained in remission for over one year on maintenance therapy with methotrexate and low-dose glucocorticoids.

Background/Objectives: Methotrexate (MTX) is a cornerstone drug used to treat immune-mediated inflammatory diseases (IMIDs) in low doses (10-30 mg/week), and malignancies in high doses (5000 mg/m2/2 weeks). Its active metabolites, Methotrexate polyglutamates (MTX-PG2-5), quantified in erythrocytes, are associated with efficacy. This study aimed to compare erythrocyte MTX-PG concentrations in patients with IMIDs and pediatric acute lymphoblastic leukemia (ped-ALL) treated with low-dose or high-dose MTX, respectively, and to identify clinical, demographic, and treatment-related factors influencing their concentration. Methods: A total of 567 patients with rheumatoid arthritis, juvenile idiopathic arthritis, Crohn's disease, sarcoidosis, and ped-ALL were included. Erythrocyte MTX-PG concentration data was collected after 3 months (2.5 months for ped-ALL patients) of MTX-use. Multivariate linear regressing modelling adjusting for age, sex, body mass index (BMI), smoking status, starting MTX dose, route of MTX administration, use of predniso(lo)ne, disease-modifying anti-rheumatic drugs (DMARDs), and folic (or folinic) acid was performed. Results: Intravenous high-dose MTX increased MTX-PG4&5 accumulation. Despite 50-fold higher doses in ped-ALL, MTX-PG2-5sum concentrations were similar to those seen with subcutaneous low-dose MTX used in IMIDs. Age positively influenced MTX-PG concentrations, while DMARD use reduced MTX-PG2-3&5 concentrations. Interestingly, predniso(lo)ne use was associated with higher MTX-PG4&5 concentrations and folic (or folinic) acid with higher MTX-PG3-5 concentrations. Conclusions: This is the first study to compare erythrocyte MTX-PG concentration in low-dose and high-dose patients. Intravenous high-dose MTX administration increased long-chain MTX-PG4&5 concentrations, with MTX-PG2-5sum concentrations similar compared to low-dose subcutaneous MTX use. This study demonstrated that route of administration, age, and concomitant therapies such as DMARDs, predniso(lo)ne, and folic (or folinic) acid significantly influence MTX-PG concentrations.

Oral methotrexate is the standard first-line treatment for rheumatoid arthritis (RA), but subcutaneous methotrexate may offer improved efficacy and tolerability and, as a second-line treatment, delay escalation to biologics. This study evaluates the cost-utility of treatment pathways including subcutaneous methotrexate versus current practice for moderate-to-severe RA in the UK. A hybrid decision tree-Markov model simulating RA treatment pathways was developed. The decision tree classified patients as (non-)responders based on American College of Rheumatology criteria. Responders continued first-line therapy; non-responders transitioned to second-line treatment. In the Markov model, states were defined by treatment line, with patient entry determined by decision tree outcomes. Transitions represented discontinuation due to inefficacy or toxicity. Health Assessment Questionnaire scores changed over time by Markov state, affecting quality of life, mortality, and hospitalisation costs. Resource use, adverse events, and treatment costs were included. Inputs were sourced from peer-reviewed literature, national costing databases, and health technology appraisals. Over 30years, the pathway including second-line subcutaneous methotrexate was projected as less costly and more effective than current practice with £5217 in total cost savings and 0.23 quality-adjusted life years gained per patient, for a net monetary benefit of £9789. One-way and probabilistic sensitivity and scenario analyses supported the robustness of results. Dominance was maintained across all variations and iterations, including a scenario with first-line subcutaneous methotrexate. Including subcutaneous methotrexate as second-line RA treatment after oral methotrexate represents effective healthcare resource use in the UK, improving patient outcomes while reducing total costs.

A 61-year-old Japanese woman with a 20-year-history of rheumatoid arthritis (RA) had been treated with various antirheumatic drugs including biologics and Janus kinase inhibitors. Subcutaneous methotrexate (MTX) was added to sarilumab, resulting in improvement in her joint tenderness. Six months later, however, while continuing both agents, she developed exertional dyspnea. Computed tomography revealed bilateral ground-glass opacities, and transbronchial lung cryobiopsy (TBLC) showed pathological findings consistent with MTX-induced pneumonitis. She responded rapidly to glucocorticoids, but subsequently developed recurrent episodes of RA-associated organizing pneumonia (RA-OP) despite discontinuation of MTX, which was evaluated by repeat bronchoscopy and supported the diagnosis of RA-OP, and prolonged glucocorticoid therapy was required. MTX-induced pneumonitis is a potentially life-threatening complication. This case demonstrates that subcutaneous MTX does not eliminate the risk of pneumonitis, that TBLC is a valuable diagnostic tool allowing clear pathological characterization with ample tissue to support confident pathologic diagnosis, and that the marked discrepancy in imaging supports that repeat bronchoscopy is warranted rather than avoided when new imaging points to an alternative diagnosis.

AGA Living Clinical Practice Guideline on the Pharmacologic Management of Moderate-to-Severe Crohn's Disease.

EE315 Cost Utility of Subcutaneous Methotrexate As a Second-Line Treatment for Moderate to Severe Rheumatoid Arthritis in the UK

Methotrexate (MTX) is a cornerstone of systemic therapy for treating moderate to severe psoriasis. It can be given orally or subcutaneously (SC). SC MTX offers higher bioavailability and more predictable exposure. However, head-to-head clinical evidence is limited. We systematically compared the efficacy and safety of SC and oral MTX to inform route selection. Building upon this background, we conducted a systematic review and network meta-analysis with random effects. Randomized controlled trials (RCTs) were identified from major databases up to 2025. Ten RCTs met the inclusion criteria. Outcomes included change in Psoriasis Area and Severity Index (PASI) from baseline, PASI 50/75/90/100 responses, and adverse events. Treatments were ranked using the Surface Under the Cumulative Ranking curve (SUCRA) probabilities. Our review and analysis showed that, across analyses, subcutaneous methotrexate (SC MTX) ranked higher than oral methotrexate (oral MTX) for PASI75 (SUCRA 0.98 vs. 0.52), PASI90 (0.98 vs. 0.39), and PASI100 (0.93 vs. 0.50). Subcutaneous methotrexate increased the odds of PASI75 (OR 5.48, 95% CI 2.53-11.85) and PASI90 (OR 3.33, 95% CI 1.09-10.13). Oral methotrexate slightly favored PASI50. Neither formulation reached significance for PASI100. Mean PASI reduction did not differ directly, despite superior rankings for subcutaneous methotrexate. Subcutaneous methotrexate was also associated with fewer adverse events and lower rates of discontinuation. SC MTX more effectively achieves PASI thresholds and is better tolerated, supporting its use as the preferred systemic treatment for moderate to severe psoriasis.

Rheumatoid arthritis is the commonest chronic inflammatory arthritis. Oral methotrexate is recommended as the first-line disease modifying drug for its management, and subcutaneous injections are typically prescribed if there is gastrointestinal intolerance or suboptimal efficacy. It is not known whether subcutaneous methotrexate is more effective and cost-effective compared to oral methotrexate when used as first-line treatment in people diagnosed with rheumatoid arthritis. The Methotrexate Oral Or SubcutanEous (MOOSE) trial aims to compare the clinical and cost-effectiveness of subcutaneous and oral methotrexate when used as first-line disease modifying anti-rheumatic drug in adults with rheumatoid arthritis and collect information about the acceptability of both routes of administration. MOOSE is an open-label, multi-centre, assessor-blinded, two-arm randomised controlled trial, with an internal feasibility assessment, economic evaluation and qualitative study. It is a secondary care-based trial, involving NHS hospital rheumatology clinics. Potentially eligible patients will be approached to participate around the time of their initial clinic visit. Eligible patients who consent will be randomised to either oral or subcutaneous methotrexate. Randomisation will be minimised by trial centre, 28-joint disease activity score, and disease duration. Interventions will be prescribed open-label with participants and clinicians aware of treatment allocated. Outcome assessors will be blinded to treatment allocation. Each participant will be in the trial for 52weeks. The primary outcome is remission assessed at 24weeks. Secondary outcomes include disease activity, quality of life, mental health and employment. A qualitative study will involve semi-structured interviews to analyse the acceptability of interventions. The health economic study will use healthcare utilisation data, quality of life data, and cost-estimates to model cost-effectiveness. Whether to use subcutaneous or oral methotrexate first line for RA is an important question for patients and clinicians. MOOSE study will provide evidence on the clinical and cost-effectiveness of oral and subcutaneous routes of methotrexate administration to answer this important question. Prospectively registered with the International Standard Randomised Controlled Trial Number (ISRCTN) 14,403,521. Registered on 03 August 2023 https://doi.org/10.1186/ISRCTN14403521 .

Abstract Introduction We describe a case of a child with systemic capillary leak syndrome (SCLS) secondary to juvenile dermatomyositis (JDM) with likely evolving macrophage activation syndrome (MAS). SCLS is a rare but serious complication of both JDM and MAS. It is characterised by fluid leakage into the extravascular tissue, resulting in anasarca, haemoconcentration, hypotension and hypoalbuminaemia. Whilst its exact pathophysiology is unknown, vasculopathy arising from cytokine-mediated endothelial damage has been posited. No common genetic association has been found. Complications include hypovolaemic shock, pulmonary oedema and compartment syndrome. Early recognition and treatment are essential to prevent end-organ damage and mortality. Case description The patient was a 12-year-old female with no significant previous medical history. She initially presented with severe proximal muscle weakness (with a childhood myositis assessment score (CMAS) of 11/52), widespread erythematous rash, Gottron papules, visibly abnormal nailfold capillaries and periungual erythema. Muscle enzymes were elevated and an MRI thigh confirmed the presence of florid myositis. Myositis antibodies were positive for anti-NXP2 antibody. She was diagnosed with juvenile dermatomyositis and was commenced on IV methylprednisolone, subcutaneous methotrexate and oral hydroxychloroquine. Following a brief period of improvement, her clinical course deteriorated. Her weakness became more profound with bulbar involvement and respiratory weakness, precipitating an aspiration pneumonia, requiring multiple courses of antibiotics and non-invasive ventilatory support. A new derangement in her biochemistry (in particular, hyperferritinaemia, hypertriglycerideaemia and elevated liver enzymes), combined with a worsening thrombocytopaenia, raised the suspicion of evolving MAS. She subsequently developed hypoalbuminaemia and anasarca (gaining up to 10kg in weight), which led to a subclinical compartment syndrome and an extremely painful exacerbation of her inflamed skin. Additionally, she developed a pre-renal acute kidney injury and electrolyte derangement. These combined findings prompted a diagnosis of secondary SCLS. Treatment was targeted at managing her underlying disease process. Following a further course of IV methylprednisolone, she received IV immunoglobulin and rituximab, alongside supportive care for her symptoms, including human albumin solution and optimised analgesia. Following a prolonged rehabilitation, she achieved a full recovery, and did not require inotropic or additional respiratory support. Discussion This case highlights a complex clinical case of JDM. SCLS is a rare complication of JDM but may have also occurred secondary to possible MAS, which in itself is also a rare complication of JDM. Whilst MAS was a consideration, atypical clinical features of worsening muscle weakness (along with elevated muscle enzymes), onset of rapid anasarca, respiratory compromise and electrolyte disturbance, prompted a wider consideration of SCLS. As far as the authors are aware, this case adds to only eight cases of SCLS secondary to JDM reported in the literature. As with our case, anasarca, respiratory complications, acute kidney injury, hypotension, haemoconcentration, hyponatraemia, hypoalbuminaemia, and worsening muscle enzymes were common variables among the reported cases. Interestingly, our case appears to be unique in describing a coincidence of suspected MAS alongside SCLS, secondary to JDM. Whilst five cases reported derangement in liver enzymes, three reported hyperferritinaemia, and one reported thrombocytopenia, none of the eight cases reported a clinical suspicion of MAS. The treatment in this case was targeted at addressing the underlying disease process with escalating immunosuppressive measures. This approach broadly correlated with the other reported cases. Corticosteroids, IV immunoglobulin and methotrexate were commonly used, whilst other options included cyclophosphamide and plasma exchange. As with our case, a common theme from the other case reports suggested corticosteroids alone are insufficient to treat SCLS as a complication of JDM, and escalation to additional immunosuppressive medication is warranted. In addition to direct treatment, involving other clinical teams (including renal, respiratory and intensive care teams) was also imperative to help manage complications. Again, this was echoed in the other case reports. Supportive symptomatic treatments for SCLS and its complications included albumin infusions, diuretics, haemodialysis, inotropes, mechanical ventilation and, in one case of severe compartment syndrome, emergency fasciotomy. Key learning points • SCLS is a rare but serious complication of JDM. Whilst localised oedema (particularly around the face) is a common presenting feature of new-onset JDM, generalised anasarca (particularly rapid onset), alongside a clinical deterioration, should prompt clinicians to consider a diagnosis of SCLS in patients with JDM. • Features to support the diagnosis might include hypoalbuminaemia, hyponatraemia and a high haematocrit. • Complications can be life-threatening. Aggressive treatment of the underlying JDM, as well as early discussions with other clinical teams to assist in managing complications of SCLS, is essential. • This case suggests concurrent MAS may partially mimic, as well as predispose to, the wider complication of SCLS. However, recognising distinguishing characteristics highlighted in this case report can help with early identification, and targeted clinical management, of SCLS.

Abstract Introduction The co-existence of dermatomyositis and myasthenia gravis is an uncommon clinical scenario that presents many diagnostic and therapeutic challenges. Such cases are sparsely documented in the literature. While both are autoimmune conditions that can present with muscle weakness, they differ significantly in their underlying pathophysiology and management strategies. We present the case of a 17-year-old male who developed a combination of rash, myalgia, progressive muscle weakness, and dysphagia. He was diagnosed with dermatomyositis and myasthenia gravis, requiring treatment with a combination of corticosteroids, immunosuppressive agents, intravenous immunoglobulin (IVIG) and pyridostigmine. Case description A 17-year-old male presented with a three month history of progressive muscle weakness, fatigue, weight loss, rash, and a three week history of dysphagia. The muscle weakness began after a flu-like illness and affected his ability to walk, lift his arms, and grip objects. He developed an erythematous rash over the metacarpophalangeal joints, elbows, back, chest, thighs, and knees. Examination revealed proximal muscle weakness (power 2/5), a low MMT8 score (79/150), and signs suggestive of myasthenia gravis, including ptosis, eye muscle fatigability, and a positive ice pack test. Skin findings included heliotrope rash, Gottron’s papules, and shawl sign. Investigations revealed creatine kinase (CK) of 618, negative antinuclear antibodies (ANA), negative myositis specific and associated antibodies, and negative 3-hydroxy-3-methylglutaryl-coA reductase (HMGCR) antibodies. Interestingly, acetylcholine receptor antibodies (AChR) were found to be positive. MRI imaging showed extensive inflammatory myopathy affecting the shoulder girdle, chest, abdominal, pelvic and thigh musculature. Nerve conduction studies were consistent with inflammatory myopathy. Muscle biopsy was suggestive of dermatomyositis with features of perifascicular atrophy, perivascular inflammatory infiltrate and occasional regenerative fibres. Barium swallow and oesophageal manometry identified cricopharyngeal spasm and a hypercontractile oesophagus. He was commenced on intravenous methylprednisolone and subsequently on oral corticosteroids. Due to progressive dysphagia, nasogastric tube insertion was warranted. Two cycles of intravenous immunoglobulins (IVIG) 2g/kg were administered 4 weeks apart and subcutaneous methotrexate and oral ciclosporin were introduced as steroid-sparing agents. Oral pyridostigmine was also commenced following input from the neurology team as there was suspected overlap with myasthenia gravis and this brought on some improvement in his symptoms. After six weeks of treatment there was clinical improvement with MMT8 score 129/150, normal CK, with resolution of the rash. Subsequently, his dysphagia also improved, allowing removal of his nasogastric tube. Discussion The overlap between dermatomyositis and myasthenia gravis is a rare clinical entity. While both are autoimmune conditions characterised by muscle weakness, their distinct pathophysiology and management strategies differ. This case highlights the rare co-existence between these two conditions. The characteristic cutaneous findings in this patient along with elevated creatine kinase levels, MRI evidence of myositis, and confirmatory muscle biopsy findings supported a diagnosis of dermatomyositis. However, the presence of mild ptosis, muscle fatigability, and a positive acetylcholine receptor antibody test indicated concurrent myasthenia gravis. The diagnosis of this overlap was critical, especially as his dysphagia persisted despite optimal immunosuppressive therapy for dermatomyositis. Management of this overlap condition poses therapeutic challenges. Dermatomyositis typically requires high-dose glucocorticoids and long-term immunosuppression, whereas treatment for myasthenia gravis includes anticholinesterases and cautious use of steroids. Notably, high-dose corticosteroids may exacerbate symptoms of myasthenia gravis in up to one-third of patients, necessitating a gradual dose escalation under close monitoring. Initial treatment for this patient included high-dose corticosteroids, IVIG, and immunosuppressive agents (methotrexate and ciclosporin), leading to partial improvement in his muscle weakness and skin rashes. However, his dysphagia remained prominent and pyridostigmine was introduced, resulting in further clinical improvement. Both idiopathic inflammatory myositis and myasthenia gravis present with muscle weakness; however, muscle fatigability, ocular muscle involvement and bulbar symptoms, such as dysphagia and dysphonia, are more common in myasthenia gravis. Nevertheless, dysphagia has been reported in one out of three patients with idiopathic inflammatory myositis, and this can occur as an initial or sole symptom and is caused by inflammatory involvement of the swallowing muscles, albeit the variation in severity of clinical manifestations and response to treatment. If dysphagia is persistent or progressive despite immunosuppressive therapy, this should prompt consideration of other underlying neuromuscular conditions. Key learning points 1. The co-occurrence of idiopathic inflammatory myopathies and myasthenia gravis is rare but should be considered in patients with atypical or refractory myositis presentations. 2. Progressive dysphagia in myositis patients, despite immunosuppressive medications, should prompt consideration of other possible neuromuscular disorders and early involvement of the relevant specialties. 3. Management of dermatomyositis/myasthenia gravis overlap should include careful use of steroids along with a trial of pyridostigmine, in addition to immune-suppressive and immune-modulatory agents. 4. Seronegative myositis does not exclude the diagnosis; muscle biopsy remains critical in confirming inflammatory myopathies. 5. IVIG has shown efficacy in treating dysphagia in both dermatomyositis alone and dermatomyositis overlap. Early, aggressive, and individualised therapy, including immunosuppression, IVIG, and treatment for myasthenia gravis, can lead to significant functional recovery.

To compare the efficacy and safety of oral and subcutaneous (SC) routes of methotrexate (MTX) administration in patients with severe psoriasis in terms of the time taken to attain a Physician Global Assessment (PGA) score of 0 or 1. Single-blinded randomised controlled trial. Place and Duration of the Study: Department of Pharmacology and Therapeutics, Army Medical College, in collaboration with Departments of Dermatology and Pathology, Pak Emirates Military Hospital, Rawalpindi, Pakistan, from January 2024 to January 2025. Patients of either gender aged between 18 and 65 years, diagnosed with severe psoriasis (PGA score of 4), were included. Patients were randomised by the lottery method into two equal groups, with 30 patients in each group. Group 1 (G-1) received oral MTX (10 to 25mg) once a week for 4 weeks, and Group 2 (G-2) received SC MTX (10 to 25mg) once a week for 4 weeks. Efficacy and safety were compared between the two groups at 0 and 4 weeks. The Chi-square and t-test were used for comparison among the groups. A total of 60 patients with a median (IQR) age of 42.0 (27.0) years; 51 (85%) were males and 9 (15%) were females. The pre-treatment PGA score was 4, while after treatment, 14 (23.3%) patients had a score of 0, 23 (38.3%) had a score of 1, 17 (28.3%) had a score of 2, and 06 (10%) had a score of 3. Both groups showed effective improvement after the treatment, with statistically significant findings (p <0.001). The SC route in the G-2 showed a greater reduction in the PGA score compared to the oral route in the G-1. Corres- pondingly, the SC route of medicine is comparatively safer than the oral route by reporting less episodes of diarrhoea (76.7% vs. 3.3%) and vomiting (26.7% vs. 6.7%). The SC route of MTX administration is safer and more effective than the oral route in patients with severe psoriasis. Efficacy and safety of methotrexate, Methotrexate, Oral route, Psoriasis, Subcutaneous route.

Effectiveness of subcutaneous methotrexate in patients with rheumatoid arthritis and its long-term persistence.

To clarify the effectiveness and safety of subcutaneous injections (SC) of methotrexate (MTX) in Japanese patients with rheumatoid arthritis using real-world data. In this retrospective observational study, 82 patients with rheumatoid arthritis were administered SC MTX at our department and affiliated facilities for 24weeks after approval in September 2022. Drug continuation rate, disease activity, clinical symptoms including adverse events, and glucocorticoid dose after SC MTX administration were retrospectively examined. The patients' background: age 59.8years, male/female 16/66, disease duration 8.6years, stage I/II/III/IV 36/32/2/11, DAS28-ESR 3.5, Clinical Disease Activity Index 10.4, and Simplified Disease Activity Index 11.2. The SC MTX continuation rate after 24weeks (primary endpoint) was 86.6%. In 72 of 82 patients (87.8%), oral MTX was switched to SC MTX. Mean oral MTX dose before the switch was 10.6mg/week. The mean maximum dose after switching to SC was 12.0mg/week. Adverse events were observed in 30 patients (36.6%), with a total Common Terminology Criteria for Adverse Events grade of 2 or lower. Clinical symptoms such as nausea, liver dysfunction, and stomatitis improved in 15 (20.8%) patients. In 53 patients who switched from oral to SC MTX, the disease activity scores were improved, and the glucocorticoid dose could be reduced. In real-world setting, switching from oral to SC MTX is useful in Japanese patients with rheumatoid arthritis.

Introduction Observational studies have shown that methotrexate, a conventional synthetic disease-modifying antirheumatic drug (csDMARD), is associated with lower arterial blood pressure (BP) and may reduce cardiovascular risk in rheumatoid arthritis (RA). However, it remains unclear whether a cause-and-effect relationship exists between the use of methotrexate and blood pressure reduction. Patients and methods We conducted a controlled comparative study of treatment-naïve newly diagnosed RA patients commenced on subcutaneous methotrexate (Group 1, n = 31, age 57 ± 15 years, 65% females, Disease Activity Score-28 – C-reactive protein, DAS28-CRP = 4.7 ± 1.2) or the DMARD comparator sulfasalazine (Group 2, n = 31, 54 ± 17 years, 61% females, DAS28-CRP = 5.0 ± 0.8). Clinic systolic (SBP, primary study endpoint) and diastolic BP (DBP) and augmentation index (AIx, a marker of arterial stiffness) were measured at baseline and after one and six months of treatment (ClinicalTrials.gov: NCT03254589). Results After six months, compared to Group 2, Group 1 patients had significantly lower SBP (−7.4 mmHg, 95% CI −14.0 to −0.8, p = 0.03). By contrast, there were no significant between-group differences in DBP (p = 0.18), AIx (p = 0.85), or DAS28-CRP (p = 0.16). A significant effect of single nucleotide polymorphisms (SNPs) rs1801133 (methyl tetrahydrofolate reductase) and rs2231142 (ATP-binding cassette subfamily G member 2) on BP changes during methotrexate treatment was observed. Conclusions This is the first comparative study showing that methotrexate significantly reduces SBP in RA. This effect did not coincide with significant changes in arterial stiffness or disease activity. Further research is warranted to investigate the mechanisms underpinning the SBP-lowering effects of methotrexate, the role of specific SNPs, and whether such effects may account for reduced cardiovascular risk in patients with RA.

ABSTRACT Purpose This study aimed to evaluate the efficacy of methotrexate (MTX) treatment in pediatric non-infectious uveitis (NIU) cases. Methods Patients diagnosed with pediatric NIU and initiated on subcutaneous MTX at a dose of 10 mg/m2/week between 2023 and 2025 were included in the study. The patients’ age, age at uveitis diagnosis, anatomical localization and etiology of uveitis, baseline and final best-corrected visual acuity (BCVA), and anterior and posterior segment complications detected at the initial visit were recorded. Results A total of 127 eyes from 64 patients were included in the study. Of these patients, 39 were female, and 25 were male. The mean age was 9.89 ± 3.56 years (3–17 years). At the initial visit, at least one ocular complication in at least one eye was detected in 49 patients. Remission was achieved in 23 cases with MTX treatment, whereas 41 patients did not achieve remission. Among the 49 patients with at least one ocular complication, remission was achieved in 13 with MTX treatment. In contrast, among the 15 patients without any complications, remission was achieved in 10 (p = 0.005). The risk of non-responsiveness to MTX treatment was found to be 10.7 times higher in patients with at least one ocular complication at diagnosis. Conclusion MTX is an effective and safe treatment for pediatric NIU. However, in a significant proportion of patients, particularly those with ocular complications, MTX alone may be insufficient, necessitating the addition of other immunosuppressive agents.

Objectives: To investigate the efficacy of low-dose methotrexate combined with topical corticosteroids and the side effects of low-dose methotrexate in patients with moderate to severe psoriasis. Methods: A descriptive, retrospective study of 31 patients diagnosed with moderate to severe psoriasis treated with a combination of low-dose methotrexate and topical corticosteroids at the Dermatology Department of Hue Central Hospital from January 2019 to June 2022. Results: 74.2% of the patients were over 50 years old, with females accounting for 58.1%. 80.6% had a disease duration of over 5 years. Erythematous plaques and scaling were prevalent, distributed across the chest, abdomen, back, and limbs. 77.4% had severe disease, with the psoriasis vulgaris and pustular forms accounting for 32.3%. Obesity and older age were the two highest risk factors. 67.7% used ultra-potent corticosteroids, 90.3% received subcutaneous methotrexate, 58.1% started with a dose of 5–10 mg/week, and 74.2% maintained a dose of 10–15 mg/week, with 45.2% using folic acid. After 4 weeks, PASI75 was achieved in 38.7%, and 87.1% showed a significant reduction in PASI levels. There was a statistically significant correlation between the rate of achieving PASI75 and age group as well as disease duration (p-values &lt; 0.05). 3.2% experienced abdominal pain, and 6.5% had elevated liver enzymes. Conclusions: The study results indicate that the combination therapy of low-dose methotrexate and topical corticosteroids helps improve clinical status in patients with moderate to severe psoriasis. The adverse effects reported were primarily abdominal pain and mild liver enzyme elevation, which did not impact treatment. However, due to the short follow-up period and low cumulative dose of methotrexate, the study could not fully assess other potential adverse events.

Aim. To present a clinical case and describe the features of dermatomyositis (DM) with myositis-specific anti-Mi2 antibodies (MSAs).Material and methods. Clinical manifestations, abnormalities of laboratory and immunologic tests, strategy and efficacy of pharmacotherapy in a patient with DM are described.Results. A clinical case of DM is presented in a patient born in 1992. The disease manifested through lesions in the skin (periorbital edema with heliotropic rash, Gottron papules, diffuse alopecia, cheilitis, digital ulcers), mucous membranes (enanthem), muscles (myalgia), joints (polyarthritis), peripheral nervous system (polyneuropathy), and constitutional symptoms (weight loss, general weakness, subfebrile temperature). Laboratory examination showed increased erythrocyte sedimentation rate of 40 mm/h and lactate dehydrogenase level of 672 U/L, antinuclear factor was measured at 1:320, and anti-Mi2 antibodies were detected by MSAs panel. Combination immunosuppressive therapy with methylprednisolone at an initial dose of 1 mg/kg/day and subcutaneous methotrexate at a dose of 15 mg/week was initiated, followed by correction depending on the clinical and laboratory dynamics. This case demonstrates benign course of anti-Mi2 antibody-positive DM. Classic skin symptoms (periorbital edema with heliotrope rash, Gottron papules) and muscle damage completely regressed after 21 months of combination pharmacotherapy with methylprednisolone and methotrexate. Stable immunological seroconversion of MSAs and drug-free clinical remission were achieved. Low risk of malignant neoplasms with this DM serotype is emphasized. Atypical symptoms of polyneuropathy and myalgia are considered.Conclusion. The presented clinical case demonstrates the characteristic features of the DM subtype with anti-Mi2 antibodies: a combination of classic skin symptoms with muscle damage, benign course during two-year combination pharmacotherapy with a glucocorticoid and a cytostatic, persistent immunological seroconversion of MSAs, drug-free clinical remission. Presumably, determination of DM serotype can be useful in clinical practice for predicting the course of the disease, response to pharmacotherapy, and the risk of developing neoplasia.

Abstract Previous post hoc analyses of randomized controlled trial data demonstrated that more patients with atopic eczema (AE) on Janus kinase (JAK) inhibitors achieve ‘super response’ (defined as total or nearly total clearance of AE) compared with dupilumab. However, there is a lack of head-to-head comparisons between conventional and novel systemic medications in patients with AE achieving super response in a real-world setting. The aim of this analysis was to explore the association between systemic medications used in patients with AE and patients achieving super response in the UK–Irish Atopic Eczema Systemic Therapy Register (A-STAR). A-STAR is a multicentre prospective observational register in the UK and Ireland aimed at evaluating the real-world effectiveness and safety of systemic treatments in AE. Patients in A-STAR who initiated conventional systemics (oral or subcutaneous methotrexate or ciclosporin), dupilumab or a JAK1 inhibitor (abrocitinib or upadacitinib) were included in this analysis. The outcomes assessed were Eczema Area and Severity Index (EASI), Peak Pruritus Numerical Rating Scale (PP-NRS) and Children’s Dermatology Life Quality Index or Dermatology Life Quality Index (C/DLQI). Patients were stratified by the medications prescribed at baseline. Super response was defined as achieving ≥ 90% improvement in EASI (EASI 90), PP-NRS of 0 or 1 (PP-NRS 0/1) and C/DLQI of 0 or 1 (C/DLQI 0/1) at any timepoint during the follow-up (censored at 500 days). Cox regression was used to assess the association between systemic medication exposure and time to achieve super response. Methotrexate was used as a reference medication. Hazard ratios and 95% confidence intervals were estimated. Risk estimates were adjusted for baseline EASI, C/DLQI, PP-NRS, ethnicity, age, sex, education level, age of AE onset, number of prior systemic treatments, concomitant oral corticosteroids and Fitzpatrick skin type. In total 649 patients were included in the analysis. The medications used were methotrexate (n = 157), ciclosporin (n = 48), dupilumab (n = 299) and JAK1 inhibitors (n = 88). The patients’ mean age was 28.7 years (SD 15.6), the mean (SD) baseline EASI was 18.2 (12.3), mean (SD) baseline PP-NRS 6.5 (2.5) and mean (SD) baseline C/DLQI 14.4 (8.1). The results for the Cox regression are summarized in the Table. Using methotrexate as the reference, both dupilumab and JAK1 inhibitors were associated with significantly more patients achieving super response in crude and adjusted models. In conclusion, treatment with dupilumab and JAK1 inhibitors is associated with a higher proportion of patients with AE achieving super response, compared with methotrexate, despite these treatments being mainly used after failure of conventional systemic medication.TableAssociation between novel systemic immunomodulatory medications and achieving super response in patients with moderate-to-severe AE. Data are expressed as the hazard ratio (95% confidence interval) CrudeAdjustedMethotrexate1 (reference)1 (reference)Ciclosporin2.25 (0.59–8.52)2.79 (0.56–13.9)Dupilumab2.20 (1.04–4.69)3.03 (1.23–7.46)JAK1 inhibitors2.75 (1.58–8.36)5.89 (2.09–16.6)

Amivantamab, an EGFR-MET bispecific antibody, is approved for multiple indications in EGFR-mutated advanced NSCLC as monotherapy or combined with other agents. Intravenous amivantamab is associated with a 67% infusion-related reaction (IRR) rate. The phase 2 SKIPPirr study (NCT05663866) enrolled participants with EGFR-mutated (exon 19 deletion or exon 21 L858R) advanced NSCLC after progression on osimertinib and platinum-based chemotherapy who received intravenous amivantamab plus oral lazertinib (amivantamab-lazertinib), a third-generation tyrosine kinase inhibitor. Aiming to mitigate IRRs, four independent prophylactic approaches were evaluated using Simon's two-stage design with an expansion stage if a cohort passed both stages: oral dexamethasone 4 mg twice daily given on cycle (C) 1 day (D) -1 (two doses); oral dexamethasone 8 mg twice daily given on C1D-2, C1D-1, and the morning of C1D1 (five doses); oral montelukast 10 mg once daily given on C1D-4, C1D-3, C1D-2, C1D-1, and C1D1 (five doses); subcutaneous methotrexate 25 mg (one dose) given anytime between C1D-7 and C1D-3. The primary end point was C1D1 IRR incidence. As of June 24, 2024, 68 participants were treated across all cohorts. The dexamethasone 8 mg cohort passed stages 1 and 2 proceeding to the expansion stage, with 24 additional participants treated. At C1D1, nine of 40 participants (22.5%) experienced IRRs, resulting in an approximately threefold decrease versus historical data (67.4%). By the end of C3, 10 of 41 participants (24.4%) in the dexamethasone 8 mg cohort experienced IRRs (grades 1-2, except one grade 3 on C2D1). Amivantamab-lazertinib's safety and efficacy were consistent with previous reports. Prophylaxis with 8 mg oral dexamethasone meaningfully reduced IRRs and can be readily implemented in clinical practice.