Purpose: To describe the use of serial intravitreal methotrexate to combat proliferative vitreoretinopathy (PVR) in a pediatric patient with recurrent retinal detachment (RD). Methods: A retrospective case analysis was performed. Results: A 6-year-old patient with bilateral panuveitis presented with recurrent RD in the right eye. After treatment with 2 RD surgeries performed elsewhere, the patient developed PVR that necessitated 5 additional surgeries for recurrent detachment. The patient subsequently received a total of 8 injections of methotrexate 400 µg/0.1 mL (0.1 mL) in the operating room at 1- to 2-week intervals over a 3-month period. Through 13 months of follow-up after the first methotrexate injection, there was no evidence of recurrent RD, PVR, or epiretinal membrane formation. Conclusions: Frequent serial intravitreal methotrexate injections apparently played a role in preventing recurrent PVR formation in this pediatric patient with a history of intraocular inflammation and recurrent RD.

OBJECTIVE: A subset of human circulating FoxP3+ regulatory T cells expresses CD39 (cTreg39+) and hydrolyses pro-inflammatory adenine nucleotides released at inflammatory foci, rendering the anti-inflammatory agent adenosine. Methotrexate (MTX), inhibiting ATIC, enhances the extrusion of adenine nucleotides and may help Treg39+ cells control inflammation. Therefore, we examined the relation of cTreg39+ cells with the effect of MTX in early Rheumatoid Arthritis (eRA).
METHODS: Freshly isolated peripheral blood lymphocytes from 98 untreated eRA patients and 98 healthy controls (HC) were examined by cytometry. Twelve months (12m) after initiating MTX, 82 patients were clinically re-evaluated and cytometry was repeated in 40 of them. The effect of MTX on Treg cell potency was assessed in Treg/Tresp cocultures.
RESULTS: The baseline (0m) cTreg39+ cell frequency was elevated in eRA above HC levels. Patients who reached low disease activity at 12 months (12m-LDA, DAS28-ESR≤ 3.2, n = 51) had presented with a significantly higher 0m cTreg39+ frequency vs those who did not (n = 31). The 0m cTreg39+ cutoff for attaining 12 m-LDA was 42.0% (Sensitivity=90.4%/Specificity=96.8%). At 12m, the cTreg39+ frequency was no longer elevated but its association with disease activity remained: it was still significantly higher in patients who had reached LDA vs those who had not. In vitro, MTX augmented the Treg39+ cell potency but had no effect on Treg39- cells.
CONCLUSIONS: MTX cooperates with Treg39+ cells and the baseline cTreg39+ frequency predicts the response to MTX in eRA. In addition, the transiently elevated baseline cTreg39+ frequency in eRA may provide a slot for prompt MTX initiation.

UNASSIGNED: Methotrexate (MTX) serves as the initial treatment for rheumatoid arthritis (RA). However, a substantial proportion of RA patients, estimated between 30% and 50%, do not respond positively to MTX. While the T-cell receptor (TCR) is crucial for the immune response during RA, its role in differentiating MTX responsiveness has not been thoroughly investigated.
UNASSIGNED: This study used next-generation sequencing to analyze the TCR β-chain complementary determining region sequences in peripheral blood mononuclear cells obtained from RA patients before MTX treatment. This study aimed to compare the characteristics of the TCR repertoire between the MTX responder and non-responder groups.
UNASSIGNED: The study identified a significant difference in the TRBV6-6 gene (p = .003) concerning MTX treatment response. Additionally, a significant difference was found in the number of \"3\" nucleotide deletions at the 5\'Jdels site (p = .023) in the VDJ rearrangement.
UNASSIGNED: These findings suggest distinct TCR repertoire characteristics between MTX responder and non-responder groups among RA patients. This discovery offers new insights into understanding the variable responses of RA patients to MTX therapy.

OBJECTIVE: To evaluate the impact of methotrexate and rituximab therapy on highly recurrent idiopathic subglottic stenosis (iSGS) patients with a negative antineutrophil cytoplasmic antibody titer cANCA(-).
METHODS: This was a retrospective cohort study of highly recurrent iSGS patients who recurred within 1 year or less and were treated with methotrexate (MTX), and rituximab (RTX), or a combination of both at different time points (MTX/RTX). Average surgical durations before and after drug treatment were summarized, and the differences were calculated.
RESULTS: A total of 21 female patients with median age of 62 years were included. Fifteen patients were treated with MTX, three were treated with RTX, and five treated with both. Patients treated with immunosuppressants showed a trend toward longer intervals between operations (mean pre-drug interval: 338; mean post-drug interval: 697 days) (p-value = 0.25). Three patients did not recur following drug initiation with median follow-up of 1265 days. All three treatment groups demonstrated a trend toward increased post-drug recurrence intervals (MTX: 444 days, RTX: 374 days, MTX/RTX: 55 days), that was not statistically significant. Patients with prior dilations demonstrated longer post-drug recurrence intervals (mean pre-drug interval: 341 days, mean post-drug interval 978 days) (p-value = 0.17). Four patients in the cohort with the highest recurring disease improved from mean 129 days between operations to 509 days with drug therapy. The most common drug side effect was nausea (16%).
CONCLUSIONS: MTX and RTX may be treatment options for some highly recurrent iSGS patients. Initial results are variable and demonstrate a need for further research on drug candidacy.
METHODS: 3 Laryngoscope, 2024.

[This corrects the article DOI: 10.3389/fphar.2023.1194578.].

BACKGROUND: Cesarean scar pregnancy is a complicated and potentially life-threatening type of ectopic pregnancy. There is no gold standard for its management. The aim is to demonstrate the efficacy and safety of treatment by hysteroscopic tissue removal system after systemic methotrexate injection.
METHODS: We report the case of a 27-year-old patient who had previously had a C-section and who presented herself to the emergency room with pelvic pain and metrorrhagia. The human chorionic gonadotrophin (hCG) serum level was positive. The exploration revealed an ectopic pregnancy on the cesarean scar. She benefited of 4 systemic injections of methotrexate. As the hCG became negative, endovaginal ultrasound confirmed the avascular nature of the mass. Surgical resection by mechanical morcellation hysteroscopy (TruClear™) was performed under general anaesthesia, visual control and ultrasound guidance.
RESULTS: This procedure was successful. It was an ambulatory procedure and there were neither intra- nor postoperative complications.
CONCLUSIONS: To our knowledge, this is the first time in Belgium that a hysteroscopic tissue removal system procedure has been used to treat a caesarean scar pregnancy. This technique seems to be safe for both the patient and the surgeon and could become a new approach for cesarean scar pregnancy management.
BACKGROUND: La grossesse sur cicatrice de césarienne est définie comme la présence d’un sac gestationnel dans une isthmocèle créée par une hystérotomie préalable. Il n’existe pas de gold standard concernant sa prise en charge. L’objectif est de démontrer l’efficacité et la sécurité du traitement par résection mécanique hystéroscopique des tissus après injection systémique de méthotrexate. Méthodes : Nous rapportons le cas d’une patiente de 27 ans ayant déjà eu une césarienne et qui s’est présentée aux urgences avec des douleurs pelviennes et des métrorragies. L’exploration révèle une grossesse sur la cicatrice de césarienne. Elle a bénéficié de 4 injections systémiques de méthotrexate. La résection des résidus trophoblastiques avasculaires a été réalisée par voie hystéroscopique en utilisant l’hystéroscope par action mécanique de type -TruClear™ et ce, sous contrôle échographique concomitant. Résultats : Cette procédure ambulatoire effectuée sous anesthésie générale a été un succès. Il n’y a eu aucune complication per- ou postopératoire.
CONCLUSIONS: À notre connaissance, c’est la première fois qu’une résection par action mécanique des résidus trophoblastiques sur cicatrice de césarienne est réalisée en Belgique. Cette technique semble sûre pour la patiente et le chirurgien et pourrait devenir une nouvelle approche pour la prise en charge d’une grossesse sur cicatrice de césarienne.

This study aimed to elucidate the incidence and characteristics of neurotoxicity in patients receiving methotrexate (MTX) treatment. A retrospective analysis was performed using data from the electronic cohort database spanning from January 1990 to December 2021. This review focused on patients who manifested neurotoxic symptoms post-MTX therapy, excluding patients with peripheral neuropathy. Of the 498 individuals who received MTX, 26 (5.22%) exhibited neurotoxicity. Pediatric patients (< 18 years) accounted for 18 cases (7.44%), whereas adults (> 18 years) comprised eight cases (3.13%). The median onset age was 11 years (range 4-15) in the pediatric cohort and 39.5 years (range 19-67) in the adult cohort. A predominant male predisposition was noted (21 patients, 80.77%). The majority of patients (21, 80.77%) experienced neurotoxic effects following multiple MTX administrations. Modes of MTX delivery included intrathecal (37.0%), intravenous (22.2%), and combined routes (40.7%). Clinical presentations were predominantly encephalopathy (69.2%), followed by encephalomyelopathy (15.4%), myelopathy (11.5%), and polyradiculopathy (3.8%). Fourteen patients recovered (53.85%). Risk factors were male sex, pediatric age (particularly above 10 years), and administration route (intrathecal in adults and intravenous in pediatrics). Although infrequent, MTX-related neurotoxicity has a substantial impact on patient prognosis, with potential development following even a single dose. Its radiological resemblance to diverse neuropathologies, such as cerebral infarction and subacute combined degeneration, necessitates vigilant diagnostic scrutiny.

BACKGROUND: The efficacy of adalimumab versus methotrexate for psoriasis remained controversial. We conducted this systematic review and meta-analysis to explore the influence of adalimumab versus methotrexate on treatment efficacy for psoriasis patients.
METHODS: We have searched PubMed, EMbase, Web of Science, EBSCO, and Cochrane Library databases through August 2023 for randomized controlled trials (RCTs) assessing the efficacy of adalimumab versus methotrexate for psoriasis. This meta-analysis was performed using the random-effect or fixed-effect model based on the heterogeneity.
RESULTS: Four RCTs and 733 patients with psoriasis were included in this meta-analysis. Overall, compared with methotrexate treatment, adalimumab treatment was associated with improved Psoriasis Area and Severity Index 75 (PASI 75, odd ratio [OR] = 4.50; 95% confidence interval [CI] = 2.81-7.22; P < .00001), physician global assessment (PGA) 0/1 response (OR = 4.86; 95% CI = 3.02-7.82; P < .00001), PASI 100 (OR = 3.01; 95% CI = 1.33-6.80; P = .008) and decreased Dermatology Life Quality Index (DLQI, standard mean difference [SMD] = -0.60; 95% CI = -0.84 to -0.36; P < .00001), but exhibited no impact on PASI 90 (OR = 3.30; 95% CI = 0.77-14.20; P = .11), adverse events (OR = 1.23; 95% CI = 0.26-5.87; P = .79) or serious adverse events (OR = 2.59; 95% CI = 0.49-13.79; P = .26).
CONCLUSIONS: Adalimumab was superior to methotrexate for the treatment of psoriasis.

OBJECTIVE: To assess the potential impact of targeted therapies for psoriatic arthritis (PsA) on symptomatic treatments (non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids, opioid analgesics), methotrexate and mood disorder treatments and on hospitalisation and sick leave.
METHODS: Using the French health insurance database, this nationwide cohort study included adults with PsA who were new users (not in the year before the index date) of targeted therapies for ≥9 months during 2015-2021. Main endpoints were difference in proportion of users of associated treatments, hospitalisations and sick leaves between 3 and 9 months after and 6 months before targeted therapy initiation. Logistic regression models adjusted for sex, age, psoriasis, inflammatory bowel disease and Charlson Comorbidity Index compared the impact of biologics initiation (tumour necrosis factor inhibitor (TNFi)/interleukin 17 inhibitor (IL17i)/IL12/23i) on associated treatment discontinuation.
RESULTS: Among 9793 patients initiating targeted therapy for PsA (mean age: 51±13 years, 47% men), 62% initiated TNFi, 14% IL17i, 10% IL12/23i, 1% Janus kinase inhibitor, 12% phosphodiesterase-4 inhibitor. After treatment initiation, the proportion of treatment users was significantly reduced for NSAIDs (-15%), opioid analgesics (-9%), prednisone (-9%), methotrexate (-15%) and mood disorder treatments (-2%), along with decreased hospitalisations (-12%) and sick leaves (-4%). TNFi had a greater sparing effect on NSAIDs and prednisone use than IL17i (ORa=1.04, 95% CI=1.01 to 1.07; 1.04, 1.02 to 1.06) and IL12/23i (1.07, 1.04 to 1.10; 1.06, 1.04 to 1.09). Odds of methotrexate discontinuation was reduced with TNFi versus IL17i (0.96, 0.94 to 0.98) and IL12/23i (0.94, 0.92 to 0.97).
CONCLUSIONS: Targeted therapy initiation for PsA reduced the use of associated treatment and healthcare, with TNFi having a slightly greater effect than IL17i and IL12/23i, except for methotrexate discontinuation.

OBJECTIVE: To investigate if patients with early rheumatoid arthritis responding insufficiently to initial methotrexate (MTX) and bridging glucocorticoids (GCs) could benefit from early but temporary etanercept introduction as a second remission-induction attempt.
METHODS: CareRA2020 (NCT03649061) was a 2-year, open-label, multicentre, pragmatic randomised controlled trial. Treatment-naïve patients started MTX and GC bridging (COBRA-Slim: CS). Within a time window from week (W) 8 until W32, early insufficient responders (28-joint Disease Activity Score - C-reactive Protein (DAS28-CRP) >3.2 between W8 and W32 or ≥2.6 at W32) were randomised to a Standard-CS strategy (adding leflunomide first) or Bio-induction-CS strategy (adding etanercept for 24 weeks). Additional treatment adaptations followed the treat-to-target principle. Longitudinal disease activity (DAS28-CRP) over 104 weeks (primary outcome), achievement of DAS28-CRP <2.6 28 weeks after randomisation, and biologic or targeted synthetic disease-modifying antirheumatic drug (b/tsDMARD) use at W104 were compared between randomisation groups.
RESULTS: Following CS treatment, 142 patients were early responders; 55 early insufficient responders received Standard-CS and 55 Bio-induction-CS. Superiority of Bio-induction-CS over Standard-CS could not be demonstrated (ß=-0.204, (95% CI -0.486 to 0.078), p=0.157) for the primary outcome. More patients on Bio-induction-CS achieved DAS28-CRP <2.6 at 28 weeks after randomisation (59% (95% CI 44% to 72%) vs 44% (95% CI 31% to 59%) in Standard-CS) and they were treated less frequently with b/tsDMARDs at W104 (19/55, 35%) compared with Standard-CS (29/55, 53%).
CONCLUSIONS: Half of the patients responded well to initial COBRA-Slim induction therapy. In early insufficient responders, adding etanercept for 6 months did not improve disease control over 104 weeks versus adding leflunomide first. However, temporary introduction of etanercept resulted in improved disease control early after randomisation and less patients on b/tsDMARDs at W104.
BACKGROUND: NCT03649061.
UNASSIGNED: S59474, EudraCT number: 2017-004054-41.