OBJECTIVE: Methotrexate (MTX) is an immunosuppressive agent used to treat noninfectious inflammatory eye conditions and is generally administered orally for ocular inflammatory diseases. When used in rheumatological diseases, subcutaneous administration has been reported to show higher efficacy than oral administration. Therefore, this study aimed to evaluate the effect of subcutaneous MTX in patients with refractory uveitis or choroiditis who did not respond to other immunosuppressive agents.
METHODS: A retrospective case series study was performed between January and December 2018. Patients with uveitis or chorioretinitis who showed little to no treatment response for 6 months or more with conventional immunosuppressive agents were treated with MTX, administered subcutaneously. After 6 months of treatment, patients were evaluated to determine whether complete suppression of inflammation sustained for ≥28 days was achieved in both eyes and whether improvement can be confirmed by fluorescein angiography (FAG).
RESULTS: Subcutaneous MTX treatment was performed on 18 patients: 11 had intermediate uveitis and seven had posterior uveitis. In the intermediate uveitis patient group, five patients (50% of the group excluding one patient who dropped out) showed improvement in FAG and three patients (30%) showed complete suppression of inflammation. In the posterior uveitis group, two out of seven patients (excluding two patients who dropped out) showed an improvement, two patients in the group showed little change, and one patient showed aggravation of FAG findings.
CONCLUSIONS: The study confirmed that in patients with uveitis or chorioretinitis who had a refractory response to treatment with other immunosuppressive agents, subcutaneous MTX showed improved treatment efficacy.

Subcutaneous (SC) methotrexate (MTX) is considered to be associated with a higher and predictable linear bioavailability as compared to oral MTX. Although various studies have reported SC MTX to be safe and effective in psoriasis, prospective head-to-head comparative trials on oral versus SC MTX are limited. To compare the efficacy and safety of SC versus oral MTX in severe psoriasis. It was a prospective, single-blinded, randomized controlled trial, in 100 eligible, adult patients of severe psoriasis randomized into two groups. Group-A (n = 50) patients were started on oral MTX at a full dose of 0.3 mg/kg/week (maximum 25 mg/week) given for 12 weeks or till achieving PASI90 [90% reduction in Psoriasis Area Severity Index (PASI) from baseline], whichever was earlier and group-B (n = 50) patients received SC MTX in the same dose and duration. MTX was then tapered gradually at 5 mg every 2 weeks and stopped. All patients were followed-up for 24 weeks post-treatment with monthly assessment of PASI and Dermatology Life Quality Index (DLQI) scores. Baseline demographic profiles of patients in both the groups were comparable. The mean ± SD baseline PASI scores were group-A: 15.1 ± 3.2 versus group-B:15.7 ± 3.3 (p = 0.35). The number of patients that achieved PASI90 at or before 12 weeks of treatment was numerically higher in group-B (39/50, 78%) versus group-A (31/50, 62%; p = 0.08) and the time to achieve PASI90 was significantly lesser (p < 0.001).Also, the percentage(%) decline in DLQI was significantly higher in group-B(p = 0.003). The overall side-effect profile was comparable between groups (p = 0.31), but the frequency of gastrointestinal side-effects was significantly less in group-B (p = 0.04). Among those patients who achieved a PASI90 response by week12, relapse rates were comparable during the subsequent 24-week follow-up period [group-A: 12/31 (39%), group-B: 11/39 (28%), and p-value = 0.33]. SC MTX results in a significantly faster achievement of PASI90 and greater reduction in DLQI as compared to oral MTX in patients who are candidates for systemic therapy with a comparable safety profile. CTRI/2018/01/011373, date of registration: 15 January, 2018; trial registered prospectively.

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Methotrexate (MTX) is one of the mainstays of treatment for several immune-mediated inflammatory joint and skin diseases, especially rheumatoid arthritis (RA) and moderate-to-severe psoriasis. Oral MTX has been used for the treatment of such diseases for decades for many reasons. There is, however, a relevant interpatient variability of clinical and safety outcomes that can also be related to differences in patients\' individual pharmacogenomic profile. Orally administered MTX has been found to have a saturable intestinal absorption and nonlinear pharmacokinetics, with significant consequences on drug bioavailability and clinical efficacy. The current evidence shows that parenterally administered MTX results in rapid and complete absorption, higher serum levels, and less variable exposure than oral dosing. The use of parenteral MTX, particularly when administered as a subcutaneous (SC) injection, has recently raised great interest in order to overcome the limitations of oral MTX. The effectiveness and safety of SC MTX have mostly been assessed in rheumatological settings, especially in patients with RA. There are only a limited number of data on SC MTX in juvenile idiopathic arthritis and even fewer in psoriatic disease. Various clinical experiences have suggested that SC MTX is more effective than oral MTX and may provide significant benefit even in patients in whom oral MTX proved to be inadequate. The increased efficacy of SC MTX resulting from higher drug exposure compared with oral MTX has been associated with a similar safety profile and in various reports even with a lower frequency of gastrointestinal complaints. The aim of this article was to review the available literature data on SC MTX treatment of inflammatory arthritis, with special emphasis on RA and psoriasis, examining differences with oral MTX treatment. A brief mention of pharmacokinetics, pharmacodynamic features and pharmacoeconomic considerations is also given.

BACKGROUND: Methotrexate (MTX) is the primary disease-modifying antirheumatic drug used for the treatment of rheumatoid arthritis (RA). Optimizing the use of oral and subcutaneous MTX may delay the use of expensive biologic therapies; the effect of such a delay on overall medical costs is currently unknown.
OBJECTIVE: To compare the 5-year healthcare costs of treatment pathways for patients with RA who initiate oral MTX in the United States.
METHODS: We identified patients with RA in the Symphony Health Solutions database (Integrated Dataverse) who initiated treatment with oral MTX in 2009 and had RA-related claims for each year through 2014. We then grouped the patients into 4 treatment cohorts, including those who (1) continued to use oral MTX, (2) switched to subcutaneous MTX, (3) switched to subcutaneous MTX and then added or switched to a biologic therapy, and (4) added or switched to a biologic therapy. The costs (in 2015 US dollars) for pharmaceuticals, office visits, hospitalizations, and emergency department visits were estimated for each cohort.
RESULTS: Of the total 35,640 patients in this study, 15,599 patients continued to use oral MTX, with an average cost of $47,464 per patient in the full study period; 1802 patients switched to subcutaneous MTX, with an average per-patient cost of $59,058; 711 patients switched to subcutaneous MTX and then added or switched to a biologic agent, with an average per-patient cost of $175,391 and a mean time to a biologic use of 1184 days; and 17,528 patients added or switched to a biologic from oral MTX, with an average per-patient cost of $212,595 and a mean time to a biologic use of 478 days. Biologic treatments were responsible for the cost differences between the cohorts; the nondrug costs were similar across the groups.
CONCLUSIONS: Our findings that patients who switched to subcutaneous MTX incurred lower costs than patients who only used oral MTX before using biologics may provide useful information for patients and providers who are choosing between continued MTX use and adding or switching to a biologic based on treatment guidelines.

A 10-year-old child presented with right eyelid swelling and a palpable orbital mass. Diagnostic evaluation with the aid of excisional biopsy revealed a pseudoencapsulated mass associated with high levels of serum perinuclear antineutrophil cytoplasmic antibodies. Family history of rheumatic diseases, response to treatment with corticosteroids and immunosuppressant drugs, and clinical and histopathologic features suggested an orbital autoimmune response in which perinuclear antineutrophil cytoplasmic antibodies were detected, and a diagnosis of probable IgG4-related disease was made.

BACKGROUND: Low-dose weekly methotrexate (MTX) is the mainstay in the therapy of rheumatoid arthritis (RA). It can be given via oral, intramuscular or subcutaneous (SC) route. This study sought to determine the real-world pattern of treatment with SC MTX in Portuguese adult patients with active RA.
METHODS: Utilization of Metoject(®) in Rheumatoid Arthritis (UMAR) was a non-interventional, cohort multicenter study with retrospective data collection. Eligible patients had active RA, at least 18 years of age, and started SC MTX treatment in 2009 or 2010 after failure or intolerance to oral MTX. Data were collected from patient\'s clinical records. Both non-parametric and parametric survival methods were used to obtain a detailed understanding of SC MTX treatment duration.
RESULTS: Fifty patients were included, of which only 9 discontinued SC MTX during the study follow-up period. The probability of discontinuation after 1, 2, and 3 years of treatment of SC MTX treatment is expected to be 6.10%, 8.50%, and 23.20%, respectively. The extrapolated median duration of SC MTX using an exponential model was 106.4 months/8.87 years. Mean dose of SC MTX was 18.36 mg. The reasons for treatment discontinuation were occurrence of adverse events in six patients and lack of efficacy in three.
CONCLUSIONS: The long treatment duration of SC MTX highlights its excellent tolerability compared to oral MTX, especially concerning the frequent adverse gastrointestinal events of MTX. Furthermore, long MTX treatment duration provides the opportunity to postpone or even avoid expensive therapies with biologics. The results obtained from the UMAR study provide important information for the utilization and public financing of SC MTX in Portugal.

Methotrexate (MTX) is the cornerstone of treatment for rheumatoid arthritis (RA), and is widely used both as first-line therapy and as an important component of long-term therapy. Although subcutaneous MTX is typically delivered orally, parenteral administration offers benefits with respect to tolerability and systemic exposure, and may be an underutilized treatment option. The RA patient population presents specific challenges for safe and accurate administration of parenteral therapies, because of common symptoms of joint pain and limited manual dexterity. These challenges may contribute to the low incidence of parenteral MTX administration. A novel MTX autoinjector (MTXAI) was recently introduced, which is designed to facilitate subcutaneous MTX self-administration among patients with RA. Here we review the development and utility of the MTXAI in the treatment of RA, and discuss how this technology may facilitate the use of subcutaneous MTX.

BACKGROUND: When treating patients with methotrexate (MTX) the most frequently reported adverse effects (AE) are gastrointestinal (GI) with nausea being reported by 10-20%. If intolerable AE of oral MTX persist, switching from oral to subcutaneous (SC) or intramuscular (IM) administration is common. However, this approach is largely empirical and the evidence is inconsistent. To our knowledge, this will be the first study to estimate the change in GI AE of switching from oral to SC MTX.
METHODS: A retrospective postal survey was sent to patients who had changed from oral MTX to SC MTX. GI AE was rated by visual analogue scale (VAS) regarding frequency and intensity of nausea, frequency of vomiting and frequency of discomfort. All participants gave informed consent. No further ethical clearance was necessary according to national law.
RESULTS: Of the sample 39/57 (68.4%) responded. Significant reductions in VAS were found in three of four primary outcome measures for GI AE. Only frequency of vomiting was not significantly reduced.
CONCLUSIONS: Our findings support the common practice of switching from oral to SC MTX to alleviate GI AE, however, additional research is needed in order to clarify this rarely studied subject.