Methotrexate Withdrawal Research Articles

Impact of concomitant methotrexate on disease activity in patients with rheumatoid arthritis tapering abatacept: results from KOBIO registry.

Tapering biologic agents can be considered for patients with stable disease activity in rheumatoid arthritis (RA). However, the specific strategy for abatacept is uncertain. This study aimed to examine the impact of tapering abatacept on disease activity in RA patients and assess the potential influence of concomitant methotrexate (MTX) treatment. Using data from the KOBIO registry, we included 505 1 year intervals from 176 patients with RA that initiated abatacept with concomitant MTX at baseline. The intervals were divided into two groups based on the dose quotient (DQ) of abatacept during each period (i.e., the tapering group (DQ < 1) and control group (DQ = 1)). The primary outcome was achieving DAS28-remission at 1 year intervals. Marginal structural models (MSM) were used to minimize confounding caused by an imbalance in time-varying variables. Abatacept was tapered at 146 (28.9%) intervals, and the mean DQ was 0.68. DAS28-remission was achieved in 207 (41.8%) intervals. Tapering abatacept did not affect the odds of achieving DAS28-remission compared with the control group (OR 1.04 [0.67-1.62]). The odds remained unaffected in the subgroup that continued MTX (OR 1.42 [0.88-2.30]) but not in the subgroup that discontinued MTX (OR 0.26 [0.10-0.57]). The effects of interaction between tapering abatacept and concomitant MTX use on DAS28 and patient's functional status showed consistent results. The incidence of adverse events within a 1 year interval was comparable between the two groups. Withdrawal of MTX while tapering abatacept may compromise meeting the treatment goal for patients with RA.

A Canadian Retrospective Chart Review Evaluating Concomitant Methotrexate De-escalation Patterns in Patients with Rheumatoid Arthritis Treated with Biologic or Targeted Synthetic DMARDs.

Rheumatoid arthritis (RA) guidelines recommend methotrexate (MTX)-anchored therapy with biologic or targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs); however, tolerability issues often lead to non-adherence. Canadian data on MTX tapering and/or withdrawal following b/tsDMARD initiation are minimal. This chart review assessed frequency of MTX tapering or withdrawal following b/tsDMARD initiation and the impact on disease status in Canadian adults with RA. Eligible patients had received MTX for ≥ 3months before b/tsDMARD initiation. The b/tsDMARD was prescribed continuously for ≥ 18months. Patients taking > 10mg/day oral prednisone or equivalent were excluded. Eight hundred eighty-nine patients (mean baseline MTX dose 19.0mg/week) prescribed b/tsDMARDs (tumor necrosis factor inhibitor 52.1%, Janus kinase inhibitor 18.3%, interleukin-6 inhibitor [IL-6i] 11.9%, other 17.7%) were evaluated at 22 Canadian centers. Within 2years of b/tsDMARD initiation, MTX was tapered in 123 (13.8%) patients and discontinued in 147 (16.5%), most commonly due to planned tapering (36.6%) and patient decision (27.2%), respectively, and most commonly with IL-6i use (34.9%). The MTX dose was unchanged for 582 (65.5%) patients and increased for 37 (4.2%). Missing data limit interpretations of MTX dose effects on some secondary endpoints and challenge the assertion that a disease activity measure-based treat-to-target approach is routinely used in Canadian rheumatology practice. Methotrexate tapering or withdrawal occurred in 30.4% of Canadians with RA within 2years following b/tsDMARD initiation. Baseline disease activity measures were missing from many medical records. However, for patients with baseline assessments, MTX tapering or discontinuation did not worsen disease activity.

A case of methotrexate-related lymphoproliferative disease showing multiple liver lesions in a patient with rheumatoid arthritis

A 66-year-old woman with rheumatoid arthritis (RA) who had been receiving methotrexate (MTX) for 2 years presented with tarry stools. Contrast-enhanced computed tomography (CT) of the abdomen revealed irregular wall thickening in the ileocecal region and multiple low-contrast masses in both lobes of the liver. Lower gastrointestinal endoscopy revealed a type 2 tumor in the ileocecal region with a semi-peripheral ulcer. Histological examination of liver and colon biopsies showed other iatrogenic immunodeficiency-associated lymphoproliferative disorder (Oi-LPD), diffuse large B-cell lymphoma type, with positivity for Epstein-Barr virus DNA. After withdrawal of MTX, the LPD lesions disappeared and the patient achieved remission. We considered this to be a sporadic case of Oi-LPD, diffuse large B-cell lymphoma type, in the liver and colon due to treatment with MTX. There has been no previous report of this condition with simultaneous hepatic and colonic lesions, and the present case is thought to be highly informative in relation to the pathogenesis.

Risk Factors Associated with Adverse Events Leading to Methotrexate Withdrawal in Elderly Rheumatoid Arthritis Patients: A Retrospective Cohort Study.

Background: Rheumatoid arthritis (RA) in elderly population represents a challenge for physicians in terms of therapeutic management. Methotrexate (MTX) is the first-line treatment among conventional synthetic-disease-modifying anti-rheumatic drugs (cs-DMARDs); however, it is often associated with adverse events (AEs). Therefore, the objective of this study was to identify the incidence and risk factors of MTX discontinuation due to AEs in elderly patients with RA in a long-term retrospective cohort study. Methods: Clinical sheets from elderly RA patients taking MTX from an outpatient rheumatology consult in a university centre were reviewed. To assess MTX persistence, we used Kaplan-Meir curves and Cox regression models to identify the risk of withdrawing MTX due to adverse events. Results: In total, 198 elderly RA patients who reported using MTX were included. Of them, the rates of definitive suspension of MTX due to AEs were 23.0% at 5 years, 35.6% at 10 years and 51.7% at 15 years. The main organs and system involved were gastrointestinal (15.7%) and mucocutaneous (3.0%). Factors associated with withdrawing MTX due to AEs were MTX dose ≥ 15 mg/wk (adjusted HR: 2.46, 95% CI: 1.22-4.96, p = 0.012); instead, the folic acid supplementation was protective for withdrawal (adjusted HR: 0.28, 95% CI: 0.16-0.49, p < 0.001). Conclusions: Higher doses of MTX increase the risk of withdrawals in elderly RA, while folic acid supplementation reduces the risk. Therefore, physicians working in therapeutic management for elderly patients using MTX must focus on using lower MTX doses together with the concomitant prescription of folic acid.

The incidence and prognosis of other iatrogenic immunodeficiency-associated lymphoproliferative disorders of the lung related to methotrexate: A retrospective study

Background and objectiveOther iatrogenic immunodeficiency-associated lymphoproliferative disorders (OIIA-LPD) are rare but well-known diseases that manifest during or after methotrexate (MTX) administration. Limited information is available on the clinical characteristics of OIIA-LPD of the lung because only a few cases have been reported. Thus, we aimed to assess the incidence and prognosis of patients with OIIA-LPD of the lung. MethodsPatients with OIIA-LPD of the lung treated at our institution between January 2008 and July 2020 were retrospectively analysed. ResultsAmong the 51 patients with OIIA-LPD, 16 (31.3%, 7 men, 9 women) had OIIA-LPD of the lung (median age, 69 [range, 63–82] years). Peripheral lesions were observed in 10 (62.5%), central lesions in two (12.5%), and both lesions in four (25.0%) patients. Nine of the 16 patients underwent bronchoscopic biopsy, seven were diagnosed (diagnostic yield, 77.8%) and, re-biopsy was performed in 2 patients. Eight (50.0%) patients had LPD and six (37.5%) had diffuse large B-cell lymphoma. In the 14 patients with confirmed treatment efficacy, the overall response rate to MTX withdrawal was 71.4%. However, chemotherapy was required in case of larger lesions (three patients). Death related to OIIA-LPD occurred in only one patient, and 11 of the 14 patients were alive during the study period (median follow-up time, 53.7 [range, 4.3–84.2] months). ConclusionThe incidence of OIIA-LPD of the lung is 31.3% and higher than that reported previously. The treatment effect of MTX withdrawal seems to be sufficient; however, in some cases, chemotherapy may be required from the beginning.

Regression of Necrotic Lesions after Methotrexate Withdrawal in Patients with Methotrexate-Associated Lymphoproliferative Disorders: A Retrospective CT Study.

This retrospective study investigated whether necrotic lesions detected on a computed tomography (CT) scan are more regressive than non-necrotic lesions after methotrexate withdrawal in patients pathologically diagnosed with methotrexate-associated lymphoproliferative disorders (MTX-LPD). In total, 89 lesions extracted from 24 patients on CT scans were included in the analysis. All patients had been evaluated for the presence of necrosis within lesions via CT scan upon first suspicion of MTX-LPD (baseline CT scan). The percentage lesion size reduction between the baseline and initial follow-up CT scan was calculated. The association between necrosis within lesions and size changes was estimated via linear regression analyses using both crude and adjusted models. Necrosis was significantly more common in extranodal lesions (27 out of 30 lesions, 90%) than in nodal lesions (9 out of 59 lesions, 15%, p<0.001). In the crude model, the regression of necrotic lesions was 58.5% greater than that of non-necrotic lesions; the difference was statistically significant (p<0.001). Additionally, the longest diameter of necrotic lesions at the baseline CT scan was significantly greater than that of non-necrotic lesions (p<0.001). Based on the adjusted model, necrotic lesions showed 49.3% greater regression than non-necrotic lesions (p=0.017). Necrosis detected on a CT scan was found to be an independent predictor of regression after MTX withdrawal in patients with MTX-LPD.

Beneficial effect of temporary methotrexate interruption on B and T cell responses upon SARS-CoV-2 vaccination in patients with rheumatoid arthritis or psoriatic arthritis

B and T cell responses were evaluated in patients with rheumatoid arthritis (RA) or psoriatic arthritis (PsA) after 1 or 2 weeks of methotrexate (MTX) withdrawal following each COVID-19 vaccine dose and compared with those who maintained MTX. Adult RA and PsA patients treated with MTX were recruited and randomly assigned to 3 groups: MTX-maintenance (n = 72), MTX-withdrawal for 1 week (n = 71) or MTX-withdrawal for 2 weeks (n = 73). Specific antibodies to several SARS-CoV-2 antigens and interferon (IFN)-γ and interleukin (IL)-21 responses were assessed. MTX withdrawal in patients without previous COVID-19 was associated with higher levels of anti-RBD IgG and neutralising antibodies, especially in the 2-week withdrawal group and with higher IFN-γ secretion upon stimulation with pools of SARS-CoV-2 S peptides. No increment of RA/PsA relapses was detected across groups. Our data indicate that two-week MTX interruption following COVID-19 vaccination in patients with RA or PsA improves humoral and cellular immune responses.

Sustained Remission and Outcomes with Abatacept plus Methotrexate Following Stepwise Dose De-escalation in Patients with Early Rheumatoid Arthritis.

One target of rheumatoid arthritis (RA) treatment is to achieve early sustained remission; over the long term, patients in sustained remission have less structural joint damage and physical disability. We evaluated Simplified Disease Activity Index (SDAI) remission with abatacept + methotrexate versus abatacept placebo + methotrexate and impact of de-escalation (DE) in anti-citrullinated protein antibody (ACPA)-positive patients with early RA. The phase IIIb, randomized, AVERT-2 two-stage study (NCT02504268) evaluated weekly abatacept + methotrexate versus abatacept placebo + methotrexate. SDAI remission (≤ 3.3) at week24. Pre-planned exploratory endpoint: maintenance of remission in patients with sustained remission (weeks40 and 52) who, from week56 for 48weeks (DE period), (1) continued combination abatacept + methotrexate, (2) tapered abatacept to every other week (EOW) + methotrexate for 24weeks with subsequent abatacept withdrawal (abatacept placebo + methotrexate), or (3) withdrew methotrexate (abatacept monotherapy). Primary study endpoint was not met: 21.3% (48/225) of patients in the combination and 16.0% (24/150) in the abatacept placebo + methotrexate arm achieved SDAI remission at week24 (p = 0.2359). There were numerical differences favoring combination therapy in clinical assessments, patient-reported outcomes (PROs) and week52 radiographic non-progression. After week56, 147 patients in sustained remission with abatacept + methotrexate were randomized (combination, n = 50; DE/withdrawal, n = 50; abatacept monotherapy, n = 47) and entered DE. At DE week48, SDAI remission (74%) and PRO improvements were mostly maintained with continued combination therapy; lower remission rates were observed with abatacept placebo + methotrexate (48.0%) and with abatacept monotherapy (57.4%). Before withdrawal, de-escalating to abatacept EOW + methotrexate preserved remission. The stringent primary endpoint was not met. However, in patients achieving sustained SDAI remission, numerically more maintained remission with continued abatacept + methotrexate versus abatacept monotherapy or withdrawal. ClinicalTrials.gov identifier, NCT02504268. Video abstract (MP4 62241 KB).

Efficacy and gastrointestinal tolerability of methotrexate in late-onset rheumatoid arthritis patients: a prospective cohort study

BackgroundThe proportion of the late-onset forms of disease is growing in rheumatoid arthritis (RA) population. Concerns about comorbidities and drug adverse events lead to delay or ineffective treatment in these patients. The aim of this study is to analyze the tolerability and efficacy of methotrexate therapy in late-onset RA (LORA) patients and compare the baseline characteristics, efficacy, and gastrointestinal (GIT) adverse effects of methotrexate treatment between LORA and young-onset RA patients (YORA).ResultsPatients whose symptoms began after 65 years or older were classified as LORA. Baseline characteristics, rheumatoid factor (RF) and anti-citrullinated protein antibody (ACPA) status, C-reactive proten (CRP) levels, disease activity scores, and radiographs of hands and feet were recorded. Patients were started to methotrexate therapy and followed for 6 months. Female gender was predominant in both LORA and YORA. LORA patients had less seropositivity (RF or anti-CCP), higher CRP levels, and higher DAS 28 scores. More than half of the patients (58%) had large joint involvement. Remission rates were higher in LORA patients, and total remission and low disease activity rates were similar. Methotrexate withdrawal due to gastrointestinal adverse events (nausea and vomiting) was lower than YORA patients. Logistic regression analysis demonstrated that DAS 28 score was the only predictor for disease remission (p: 0.000), and no predictive factor was found for methotrexate-related adverse events.ConclusionMethotrexate-related gastrointestinal adverse events do not increase in LORA patients, and nausea-vomiting is seen lower than YORA. Methotrexate is well tolerated and effective in LORA patients, and a large amount of patients achieve treatment targets after 6 months of treatment with MTX. Methotrexate should be started immediately in LORA without additional concerns on adverse effects.

Analysis of Disease Activity Metrics in a Methotrexate Withdrawal Study among Patients with Rheumatoid Arthritis Treated with Tofacitinib plus Methotrexate.

The objective of this analysis was to assess disease activity metrics using a variety of disease outcome measures following methotrexate (MTX) withdrawal in ORAL Shift, a phase 3b/4 study of tofacitinib with/without MTX, in patients with rheumatoid arthritis (RA) achieving Clinical Disease Activity Index (CDAI)-defined low disease activity (LDA). Patients aged ≥ 18years with active RA and an inadequate response to MTX received open-label tofacitinib modified-release 11mg once daily plus MTX for 24weeks. In the double-blind MTX withdrawal phase, those who had achieved CDAI LDA (≤ 10) at week 24 were randomised 1:1 to receive tofacitinib monotherapy or continued tofacitinib plus MTX. Efficacy analyses were performed in subgroups defined by whether remission and/or LDA had been achieved at week 24 with: Disease Activity Score in 28 joints, erythrocyte sedimentation rate [DAS28-4(ESR)], Routine Assessment of Patient Index Data 3 (RAPID3), CDAI and Simplified Disease Activity Index (SDAI); or DAS28-4[C-reactive protein(CRP)] < 2.4/ < 2.6/ < 2.9/ ≤ 3.2. Five hundred and thirty patients received treatment in the double-blind MTX withdrawal phase. Proportions of patients achieving each disease activity criterion at week 24 varied by metric. Across disease activity metrics [excluding DAS28-4(ESR) remission], 58-89% of patients per group, and numerically more patients receiving tofacitinib plus MTX, achieved the same criterion at week 48 as at week 24. Differences between groups in least squares mean change from baseline (Δ) DAS28-4(ESR) from week 24-48 favoured tofacitinib plus MTX (nominal pvalues < 0.05). RAPID3 and DAS28-4(CRP) estimated a higher proportion of patients with acceptable disease state versus DAS28-4(ESR), CDAI remission and SDAI remission. Response rates at the beginning of the double-blind phase varied across metrics. A consistent trend towards higher response rates with tofacitinib plus MTX was observed across metrics after randomisation, with nominal differences in DAS28-4(ESR) responses. Compared with continued combination therapy, MTX withdrawal did not lead to a clinically meaningful reduction in the response to tofacitinib. DAS28-4(CRP) and RAPID3 were the least stringent metrics. ClinicalTrials.gov identifier: NCT02831855.

Methotrexate-Associated Lymphoproliferative Disorder With Gingival Swelling

A 63-year-old Japanese man being treated for pemphigus vulgaris with methotrexate (MTX) presented with a fever of unknown origin. His only symptom at onset was mild gingival swelling. Suspected to have gingivitis, he was followed for 1 month. After that, he presented with cervical lymphadenopathy, dysphagia, and bicytopenia, and a diagnosis of MTX-associated lymphoproliferative disorder (MTX-LPD) was finally made by gingival biopsy. He had spontaneous remission after the withdrawal of MTX. When MTX-treated patients complain of fever and oral lesions, even if the oral lesions present as mild gingival swellings, physicians should consider MTX-LPD and perform a diagnostic biopsy.

32 Methotrexate in oligoarticular juvenile idiopathic arthritis: adverse effects and outcome

Abstract Background Methotrexate (MTX) is the anti-rheumatic drug of choice in juvenile idiopathic arthritis (JIA). Its adverse effects such as intolerance occur frequently, potentially hindering its efficacy Objective To describe the frequency of MTX intolerance and its various adverse effects (AE). Results A retrospective study was conducted on the AEs associated with MTX therapy in children diagnosed with oligoarticular juvenile idiopathic arthritis followed-up at the paediatric emergency and outpatient department of the children's hospital in Tunisia between January 2005 and December 2021. Among 95 cases, only 70 patients were included into the study, of whom 55 (78.5%) were girls. The median age at diagnosis was 5.9 years. Of these, 39/70 (55.7%) had required the use of MTX. The use of MTX was early (within the first 6 months after diagnosis) in 61.5% of cases. The initial median weekly dose was 11.4 mg/m². MTX intolerance was noted in 35.8% of cases. Management of intolerance included change in the dose, education and counselling. Adverse events led to MTX withdrawal in only one patient (2.5%). The adverse effects noted during the follow-up were mainly transient increased plasma transaminases (17.9%), gastrointestinal symptoms (10.2%) and cytopenia (7.6%). Impairment of kidney function and behavioural problems were not noted in any of our patients. The medium duration of the treatment was 3.8 years. The evolution was marked by the occurrence of a relapse of the disease after discontinuation of MTX in 14/33 cases (42.4%). The addition of biotherapy was necessary in 10/39 cases (25.6%). Only 7% of children have persistent joint stiffness or deformity. Conclusion In JIA, it is important to start effective treatment early to avoid long-term sequelae, such as joint damage. MTX adverse effects such as MTX intolerance occur frequently, potentially hindering its efficacy. To avoid inefficacy, the physician should be timely aware of these adverse events.

Optimizing methotrexate withdrawal during COVID vaccination.

Optimizing methotrexate withdrawal during COVID vaccination.

Impact of Methotrexate Discontinuation, Interruption, or Persistence in US Patients with Rheumatoid Arthritis Initiating Tofacitinib + Oral Methotrexate Combination

PurposeUsing data from real-world practice, this analysis compared outcomes in patients with rheumatoid arthritis (RA) initiating treatment with an oral Janus kinase inhibitor, tofacitinib, in combination with persistent, discontinued, or interrupted treatment with oral methotrexate (MTX). MethodsThis retrospective claims analysis (MarketScan® databases) included data from US patients with RA and at least one prescription claim for tofacitinib, dated between January 1, 2013, and April 30, 2017. Eligible patients were continuously enrolled for ≥12 months before and after treatment initiation, and initiated tofacitinib in combination with oral MTX, with at least two prescription claims for each. Patients were grouped according to treatment pattern (MTX-Persistent, MTX-Discontinued, or MTX-Interrupted). Tofacitinib treatment persistence, adherence, and effectiveness, as well as all-cause and RA-related health care costs, were assessed. FindingsA total of 671 patients were eligible for inclusion; 504 (75.1%) were MTX-Persistent; 131 (19.5%), MTX-Discontinued; and 36 (5.4%), MTX-Interrupted. Rates of tofacitinib treatment persistence, adherence, and effectiveness at 12 months were similar between the MTX-Persistent and MTX-Discontinued cohorts. The percentage of patients switched from tofacitinib to another advanced disease-modifying antirheumatic drug within 12 months of tofacitinib initiation was greater in the MTX-Persistent cohort compared with that in the MTX-Discontinued cohort. RA-related health care costs at 12 months post-initiation were significantly greater in the MTX-Persistent cohort compared with those in the MTX-Discontinued cohort. ImplicationsThe findings from this analysis of real-world data indicate that patients who initiate tofacitinib in combination with oral MTX may discontinue MTX and still experience outcomes similar to those in patients who persist with MTX, with lesser RA-related health care costs. These results support those from a previous clinical study on methotrexate withdrawal in patients with RA (NCT02831855).

POS0288 A CANADIAN RETROSPECTIVE CHART REVIEW EVALUATING CONCOMITANT METHOTREXATE DE-ESCALATION PATTERNS IN RA PATIENTS TREATED WITH BIOLOGIC OR TARGETED SYNTHETIC DMARDS

POS0288 A CANADIAN RETROSPECTIVE CHART REVIEW EVALUATING CONCOMITANT METHOTREXATE DE-ESCALATION PATTERNS IN RA PATIENTS TREATED WITH BIOLOGIC OR TARGETED SYNTHETIC DMARDS

Two-week methotrexate discontinuation in patients with rheumatoid arthritis vaccinated with inactivated SARS-CoV-2 vaccine: a randomised clinical trial

ObjectiveTo evaluate the effect on immunogenicity and safety of 2-week methotrexate (MTX) discontinuation after each dose of the Sinovac-CoronaVac vaccine versus MTX maintenance in patients with rheumatoid arthritis (RA).MethodsThis was...

Spontaneous regression of breast lymphoproliferative disorders after withdrawal of methotrexate in rheumatoid arthritis patients with Epstein\u2013Barr virus infection: a case report and review of the\xa0literature

BackgroundLymphoproliferative disorder (LPD) has been shown to occur after treatment with methotrexate (MTX). Currently, MTX-LPD has become widely recognized, but its mechanism and prognostic factors remain unclear.Case presentationWe report the first case of Epstein–Barr virus (EBV)-associated MTX-LPD of the breast. A 63-year-old Asian woman with long-term rheumatoid arthritis presented to our facility with intermittent fever. A physical examination revealed a 3-cm lump in her left breast. She had been taking MTX for the past 15 years. Laboratory studies revealed slightly elevated levels of EBV-viral capsid antigen antibody immunoglobulin G and EBV nuclear antibody. Contrast-enhanced computer tomography revealed a mass in the left breast, a subcutaneous nodule in the abdomen, a mass in the left lung, and a nodule in the left retroperitoneum. The definitive diagnosis was consistent with MTX-LPD merging into an EBV-positive, diffuse large B-cell lymphoma. Six months following the withdrawal of MTX, the breast mass had markedly shrunk and the patient remained in good health for 1 year with no evidence of relapse of LPD.ConclusionMTX-LPD rarely occurs in the breast, and it is difficult to diagnose because there have only been six reported cases of breast MTX-LPD reported in the literature. EBV-positive MTX-LPD tends to regress spontaneously after MTX withdrawal, and our case also had similar results. It is important to make an appropriate diagnosis of MTX-LPD of the breast based on imaging and pathology to determine the appropriate treatment protocol for this rare disorder.

Hypercalcemia with methotrexate pneumonitis: A rare, important and intriguing adverse event.

Methotrexate leading to hypercalcaemia is a rarely reported adverse event. We present three elderly patients with inflammatory arthritis who developed hypercalcemia probably due to methotrexate-induced granulomatous pneumonitis. All patients presented with worsening non-productive cough with dyspnea, nausea, loss of appetite, and confusion. Their clinical and radiologic features were consistent with methotrexate-induced pneumonitis. On evaluation, all patients concurrently had hypercalcemia with normal 25OH D3, and low PTH with markedly elevated levels of 1,25OH D3 seen in two patients. In all three patients, hypercalcemia and pneumonia responded to hydration, corticosteroids, and methotrexate withdrawal. There was no relapse of symptoms on long term follow-up. In these three patients with inflammatory arthritis, methotrexate-induced pneumonitis led to symptomatic hypercalcemia. Unless hypercalcemia is looked for and treated in this setting, the morbidity can be high.

Is there still a place for methotrexate in severe psoriatic arthritis?

The management of psoriatic arthritis (PsA) has long been equated with that of rheumatoid arthritis (RA), particularly because methotrexate (MTX) was found efficient in RA in the 1990s. However, results of collective evidence-based medicine, included and argued in this narrative review, do not currently support the use of MTX as first-line therapy in severe PsA. A recent Cochrane systematic review examining the efficacy of MTX in PsA concluded that low-dose MTX was only slightly more effective than placebo. Questions about a structural effect of MTX in PsA remains non-elucidated. Even if tolerance data on MTX are more consensual and adverse events generally non-severe, subjective side effects such as fatigue might lead to MTX withdrawal based on the patient’s decision. PsA patients with axial disease, radiographic lesions, and extensive and disabling skin or joint involvement should receive early treatment with targeted therapy and no longer with MTX. Finally, the usefulness of MTX combined with targeted therapies is limited. MTX does not affect efficacy but only seems to increase the therapeutic maintenance of monoclonal TNF inhibitors. This narrative review may help clarify the place of MTX in PsA management. It allows for reflection on the evolution of current concepts and practices.

Methotrexate related cutaneous adverse drug reactions: a systematic literature review.

Recently, there is an increased number of reports being published on Methotrexate (MTX) related cutaneous manifestations. We aimed to identify and critically appraise descriptive studies describing the MTX related skin manifestations, treatment approach, and their outcomes. An extensive literature search was performed in the PubMed, Embase, and Scopus databases from inception to April 2021 without any restrictions along with the bibliographic search of included studies, grey literature search, and a snowball search was performed in Google and Google Scholar to identify the relevant literature. Descriptive studies reporting MTX related cutaneous manifestations were considered for the review. The study selection, data extraction, and quality assessment were conducted by two independent reviewers and any disagreements were settled by consensus with the third reviewer. 31 out of 8,365 descriptive studies including 38 patients (22 females and 16 males) aged between 12 and 78years prescribed for the management of rheumatoid arthritis, ankylosing spondylitis, and psoriasis were included in this review. Toxic epidermal necrolysis (TEN), papular eruption, vasculitis, erosions of psoriasis, ulcerated psoriatic plaques, local reactions, keratinocyte dystrophy, erythema multiforme, drug rash with eosinophilia and systemic symptoms, Steven Johnson syndrome and photosensitive dermatitis were the majority of MTX induced cutaneous reactions. Immediate withdrawal of MTX, providing appropriate care with anti-inflammatory, topical steroids, and supplementation with folic acid were reported to be effective for the management of the MTX related cutaneous manifestations. Clinicians and healthcare professionals should be aware of possible acute cutaneous drug reactions induced by MTX to avoid further consequences and fatal conditions. Immediate withdrawal of MTX and supportive care were reported as an efficacious therapeutic management of acute cutaneous drug reactions. CRD42020220038.