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PubMed1988

Anal submucosal injection: a new route for drug administration in pelvic malignancies. II. Methotrexate anal injection in the treatment of advanced bladder cancer. Preliminary study.

The clinical efficacy of submucosal anal injections of methotrexate in advanced bladder cancer is investigated. An experimental study on 20 mice has shown that methotrexate injected into the anal submucosa has no clinicopathological effect on the anorectum. The clinical study comprised 18 patients with advanced bladder cancer (13 with stage T3 and 5 with stage T4 disease) as a test group in whom methotrexate was injected into the anal submucosa and 8 (6 with stage T3 and 2 with stage T4 cancer) treated concurrently with intravenous methotrexate. The dose in both groups was 50 mg. every 5 days for 5 consecutive doses. The course was repeated at 3-week intervals. Most patients received methotrexate as outpatients. Methotrexate blood levels were measured 4 and 24 hours after administration in both groups. In the test group 10 of the 18 patients showed complete tumor regression and were alive 21 to 50 months after the start of treatment. Partial regression was observed in 8 patients. Hematological reserve remained unchanged. Mild toxicity occurred in 3 patients. Of the 8 patients treated intravenously the tumor showed partial regression in 1, was stable in 3 and progressed in 4. Side effects were severe in 5 patients. Our results show that methotrexate injection is highly effective in the treatment of advanced bladder cancer. It is safe, well tolerated and can be used on an outpatient basis.

Adult↗

PubMed1998

Induction of cytogenetic damage in human lymphocytes in vitro and of antineoplastic effects in Ehrlich ascites tumor cells in vivo treated by methotrexate, hyperthermia and/or caffeine.

The synergistic effect of methotrexate (at concentrations between 3. 1 and 100 nM) and its combinations with caffeine (618 microM) and/or hyperthermia (42 degreesC for 2 h) on the frequency of sister chromatid exchanges (SCEs), the proliferating rate index and the mitotic index in cultured human lymphocytes, was examined. Also, the in vivo antineoplastic effects of methotrexate (at a concentration of 0.45 microg/g body weight) and its combination with caffeine (120 microg/g body weight), both on the survival time and the increase of the weight of tumor of BALB/c mice inoculated with Ehrlich ascites tumor cells was examined in the present study. The results indicated that: (a) the triple combination of methotrexate, caffeine and hyperthermia synergistically increased the levels of SCEs and exerted cytostatic and cytotoxic action and (b) the combination of methotrexate and caffeine significantly increased the survival span of the mice inoculated with Ehrlich ascites tumor cells and reduced the increase of the weight of their tumors at rates higher than in the case of methotrexate by itself. It is suggested that the above triple combination (methotrexate plus caffeine plus hyperthermia) could achieve increased effectiveness of methotrexate, better therapy results, and could be successfully applied in the treatment of various types of cancer.

Adolescent↗

PubMed2002

Role of intravitreal methotrexate in the management of primary central nervous system lymphoma with ocular involvement.

PURPOSE: To evaluate the safety and efficacy of intravitreal methotrexate in the management of primary central nervous system lymphoma (PCNSL) involving the eye. DESIGN: Retrospective noncomparative interventional case series. PARTICIPANTS: Sixteen human immunodeficiency virus-negative white patients (5 males and 11 females, aged 30-76 years) with intraocular B cell lymphoma treated with intravitreal methotrexate at Oregon Health & Science University or Hadassah University Hospital between August 1995 and September 2000. INTERVENTION: Patients were treated with intravitreal methotrexate (400 micro g/0.1 ml) according to a standard induction-consolidation-maintenance regimen and monitored by serial examinations, including measurement of visual acuity, slit-lamp biomicroscopy, and dilated funduscopy. MAIN OUTCOME MEASURES: Clinical response to intravitreal chemotherapy, number of injections for clinical remission, visual acuity, complications during study period, length of survival from diagnosis, and cause of death. RESULTS: Time of follow-up from commencement of the methotrexate injections was 6 to 35 months (median, 18.5 months). Twenty-six of 26 eyes (100%) were cleared clinically of malignant cells after a maximum of 12 methotrexate injections. A second remission was induced in three patients, who were treated with a further course of intravitreal chemotherapy after their tumor recurred within the eye. Complications that occurred during the period of treatment and follow-up included cataract (73% of 26 eyes), corneal epitheliopathy (58% of 26 eyes), maculopathy (42% of 26 eyes), vitreous hemorrhage (8% of 26 eyes), optic atrophy (4% of 26 eyes), and sterile endophthalmitis (4% of 26 eyes). No patient had irreversible loss of vision that could be definitely attributed to the intravitreal injection of methotrexate. CONCLUSIONS: Intravitreal chemotherapy with methotrexate is effective in inducing clinical remission of intraocular tumor in PCNSL with acceptable morbidity. Further study is indicated to determine whether this approach extends life expectancy.

Adult↗

PubMed1982

Combined methotrexate--ultraviolet B therapy in the treatment of psoriasis.

Twenty-six patients with extensive psoriasis were treated with a 3-week course of methotrexate followed by a combination of ultraviolet B (UVB) therapy and methotrexate. A plaque of psoriasis was shielded during UV therapy to serve as a control. When lesions cleared to less than 5% of body involvement, the methotrexate was stopped and UVB therapy alone was used as maintenance therapy. This protocol achieved clearance of disease in all twenty-six patients in a mean of 7 (+/- 1.5) weeks, with twelve (+/- 4.0) exposures to UVB therapy and a final UVB radiation dose at clearance of 320 (+/- 157) mjoules/cm2. The mean total dose of methotrexate was 112 mg (range, 75 mg-165 mg). At the time of clearing, the shielded area had a decrease in sealing and thickness in twenty-two patients but was free of psoriasis in only four patients. In a preliminary study we were unable to reproduce a methotrexate recall of UV-induced erythema. The combination therapy of methotrexate and UVB allows for clearing of psoriasis at relatively low doses of UVB and methotrexate, and thus may reduce the long-term cumulative toxicity of both agents.

Adult↗

PubMed1996

Methotrexate is effective therapy for lymphomatoid papulosis and other primary cutaneous CD30-positive lymphoproliferative disorders.

BACKGROUND: The spectrum of primary cutaneous CD30+ lymphoproliferative disease consists of lymphomatoid papulosis (LyP) at one extreme and CD30+ peripheral T-cell lymphoma (Ki-1+ lymphoma) presenting in the skin at the other extreme. Methotrexate has been reported to be effective in LyP, but the experience has been limited to single case reports or small series. OBJECTIVE: The objective was to determine the effectiveness of methotrexate in the treatment of primary cutaneous DC30+ lymphoproliferative disease. METHODS: We reviewed our 20-year experience with the use of methotrexate in 45 patients with relatively severe LyP, Ki-1+ lymphoma, and interface presentations. RESULTS: During induction of methotrexate therapy patients received maximum doses ranging from 10 to 60 mg/week (median, 20 mg/week). Clinical improvement usually occurred quickly, typically at doses of 15 to 20 mg weekly, and satisfactory long-term control was achieved in 39 patients (87%) with maintainance doses given at 10 to 14-day intervals (range, 7 to 28 days). After methotrexate was discontinued, 10 patients remained free of CD30+ lesions from more than 24 months to more than 227 months (median, more than 127 months). The median total duration of methotrexate therapy for all patients exceeded 39 months (range, 2 to 205 months). Adverse effects were generally mild and transient and included fatigue (47%), nausea (22%), weight loss (13%), diarrhea or gastrointestinal cramping (10%), increased serum hepatic transaminase levels (27%), anemia (11%), or leukopenia (9%). Early hepatic fibrosis was found in 5 of 10 patients, all of whom had been treated for more than 3 years (range, 38 to 111 months). CONCLUSION: Low-dose methotrexate (25 mg or less given at 1-to 4-week intervals) is an effective and well-tolerated treatment of selected patients with primary cutaneous CD30+ lymphoproliferative disease.

Adult↗

PubMed1999

[Methotrexate in dermatology: pharmacology, indications, applications and prudent use].

High dosage methotrexate is currently used in the treatment of malignancies. When used at low- or moderate doses, methotrexate has antiproliferative and antiinflammatory effects and is a useful drug in skin diseases. The aim of this review is to describe pharmacology, indications, adverse effects and practical use in Dermatology. Pharmacodynamics of methotrexate is especially related to antifolic activity. Methotrexate is officially approved in the treatment of severe psoriasis, but many other proliferative or inflammatory diseases with cutaneous manifestations may benefit from this drug, usually in association with corticosteroids. The use of methotrexate needs some precautions and a precise follow-up to minimise the risk of severe adverse effects. However, efficacy of methotrexate was reported in open and retrospective small size studies. Prospective and comparative trials are required to confirm the indications, advantages and tolerance of methotrexate in dermatology.

Anti-Inflammatory Agents↗

PubMed1985

Efficacy of low-dose methotrexate in rheumatoid arthritis.

Twenty-eight patients with refractory rheumatoid arthritis completed a randomized 24-week double-blind crossover trial comparing oral methotrexate (2.5 to 5 mg every 12 hours for three doses weekly) with placebo. The methotrexate group had significant reductions (P less than 0.01 as compared with the placebo group) in the number of tender or painful joints, the duration of morning stiffness, and disease activity according to physician and patient assessments at the 12-week crossover visit; reductions in the number of swollen joints (P less than 0.05) and 15-m walking time (P less than 0.03) also occurred. These variables, as well as the grip strength and erythrocyte sedimentation rate, showed significant (P less than 0.01) improvement at 24 weeks in the population crossed over to methotrexate. A significantly increased frequency (P less than 0.03) of the HLA-DR2 haplotype occurred in the eight patients with the most substantial response to methotrexate. Adverse reactions during methotrexate therapy included transaminase elevation (21 per cent), nausea (18 per cent), and diarrhea (12 per cent); one patient was withdrawn from the trial because of diarrhea. One patient died while receiving the placebo. Methotrexate did not affect measures of humoral or cellular immunity. We conclude that this trial provides evidence of the short-term efficacy of methotrexate in rheumatoid arthritis, but the mechanism of action is unknown. Longer trials will be required to determine the ultimate safety and effectiveness of this drug.

Administration, Oral↗

PubMed1996

Treatment of rheumatoid arthritis with methotrexate alone, sulfasalazine and hydroxychloroquine, or a combination of all three medications.

BACKGROUND: Rheumatoid arthritis is a common disease that causes substantial morbidity and mortality. The responses of patients with rheumatoid arthritis to treatment with a single so-called disease-modifying drug, such as methotrexate, are often suboptimal. Despite limited data, many patients are treated with combinations of these drugs. METHODS: We enrolled 102 patients with rheumatoid arthritis and poor responses to at least one disease-modifying drug in a two-year, double-blind, randomized study of treatment with methotrexate alone (7.5 to 17.5 mg per week), the combination of sulfasalazine (500 mg twice daily) and hydroxychloroquine (200 mg twice daily), or all three drugs. The dose of methotrexate was adjusted in an attempt to achieve remission in all patients. The primary and point of the study was the successful completion of two years of treatment with 50 percent improvement in composite symptoms of arthritis and no evidence of drug toxicity. RESULTS: Fifty of the 102 patients had 50 percent improvement at nine months and maintained at least that degree of improvement for two years without evidence of major drug toxicity. Among them were 24 of 31 patients treated with all three drugs (77 percent), 12 of 36 patients treated with methotrexate alone (33 percent, P < 0.001 for the comparison with the three-drug group), and 14 of 35 patients treated with sulfasalazine and hydroxychloroquine (40 percent), P = 0.003 for the comparison with the three-drug group). Seven patients in the methotrexate group and three patients in each of the other two groups discontinued treatment because of drug toxicity. CONCLUSIONS: In patients with rheumatoid arthritis, combination therapy with methotrexate, sulfasalazine, and hydroxychloroquine is more effective than either methotrexate alone or a combination of sulfasalazine, and hydroxychloroquine.

Adult↗

PubMed2005

Leflunomide or methotrexate for juvenile rheumatoid arthritis.

BACKGROUND: We compared the safety and efficacy of leflunomide with that of methotrexate in the treatment of polyarticular juvenile rheumatoid arthritis in a multinational, randomized, controlled trial. METHODS: Patients 3 to 17 years of age received leflunomide or methotrexate for 16 weeks in a double-dummy, blinded fashion, followed by a 32-week blinded extension. The rates of American College of Rheumatology Pediatric 30 percent responses (ACR Pedi 30) and the Percent Improvement Index were assessed at baseline and every 4 weeks for 16 weeks and every 8 weeks during the 32-week extension study. RESULTS: Of 94 patients randomized, 86 completed 16 weeks of treatment, 70 of whom entered the extension study. At week 16, more patients in the methotrexate group than in the leflunomide group had an ACR Pedi 30 response (89 percent vs. 68 percent, P=0.02), whereas the values for the Percent Improvement Index did not differ significantly (-52.87 percent vs. -44.41 percent, P=0.18). In both groups, the improvements achieved at week 16 were maintained at week 48. The most common adverse events in both groups included gastrointestinal symptoms, headache, and nasopharyngeal symptoms. Aminotransferase elevations were more frequent with methotrexate than with leflunomide during the initial study and the extension study. CONCLUSIONS: In patients with polyarticular juvenile rheumatoid arthritis, methotrexate and leflunomide both resulted in high rates of clinical improvement, but the rate was slightly greater for methotrexate. At the doses used in this study, methotrexate was more effective than leflunomide.

Administration, Oral↗

PubMed2000

Methotrexate infusion in low-risk gestational trophoblastic disease.

OBJECTIVES: The current study attempts to evaluate the effectiveness of methotrexate infusion therapy in the management of low-risk gestational trophoblastic disease and to find out whether an increase in the dose intensity can effect a faster remission and a shorter treatment duration. STUDY DESIGN: This is a prospective study. Between June 1990 and August 1998, 59 patients with low-risk trophoblastic disease were treated with methotrexate at a dose of 100 mg/m(2) as an intravenous bolus over 30 minutes followed by a 12-hour infusion of methotrexate at a dose of 200 mg/m(2). Folinic acid was not given unless the serum methotrexate reached a toxic level 24 hours after infusion (toxic level, 10 micromol/L). Actinomycin D was added in patients with a partial response. The follow-up period of these patients ranged from 12 to 113 months, with a median of 58.5 months and a mean of 55.7 months. RESULTS: Fifty-four patients attained a complete biochemical remission. Twenty-eight patients went into biochemical remission after one methotrexate infusion. Five patients showed a partial biochemical response. A relapse developed in 2 of the 54 complete responders at 3 months and 18 months after the initial therapy. Both patients received combination therapy consisting of methotrexate, etoposide, and bleomycin. They went into biochemical remission and have remained disease-free at the time of analysis. All of the 59 patients were in biochemical remission at the time of analysis. No significant side effects were observed except that Stevens-Johnson syndrome developed in 1 patient. CONCLUSIONS: Methotrexate infusion therapy described in this study is effective in the treatment of low-risk gestational trophoblastic disease. The omission of consolidation therapy and folinic acid rescue decreases the cost and duration of treatment.

Adult↗

PubMed2002

Interaction of dihydrofolate reductase with methotrexate: ensemble and single-molecule kinetics.

The thermodynamics and kinetics of the interaction of dihydrofolate reductase (DHFR) with methotrexate have been studied by using fluorescence, stopped-flow, and single-molecule methods. DHFR was modified to permit the covalent addition of a fluorescent molecule, Alexa 488, and a biotin at the N terminus of the molecule. The fluorescent molecule was placed on a protein loop that closes over methotrexate when binding occurs, thus causing a quenching of the fluorescence. The biotin was used to attach the enzyme in an active form to a glass surface for single-molecule studies. The equilibrium dissociation constant for the binding of methotrexate to the enzyme is 9.5 nM. The stopped-flow studies revealed that methotrexate binds to two different conformations of the enzyme, and the association and dissociation rate constants were determined. The single-molecule investigation revealed a conformational change in the enzyme-methotrexate complex that was not observed in the stopped-flow studies. The ensemble averaged rate constants for this conformation change in both directions is about 2-4 s(-1) and is attributed to the opening and closing of the enzyme loop over the bound methotrexate. Thus the mechanism of methotrexate binding to DHFR involves multiple steps and protein conformational changes.

Base Sequence↗

PubMed1984

Accumulation of DNA strand breaks and methotrexate cytotoxicity.

There was a progressive formation of strand breaks in mature DNA of Ehrlich ascites tumor cells that were treated with methotrexate. Cells were labeled with [14C]thymidine before incubation with methotrexate, and DNA strand breaks were measured by alkaline and by neutral filter elution methods. DNA single-strand breaks accumulated in a linear fashion as a function of time during the first 10 hr of incubation with 2 microM methotrexate. Thereafter, the accumulation of DNA strand breaks deviated from linearity because of progressive cell death. The extent of DNA strand breakage in cells that had been incubated with methotrexate for 24 hr was as high as in cells that had been irradiated with 300 rads. DNA strand breaks persisted in cells that were incubated, after exposure to methotrexate, in medium containing thymidine, hypoxanthine, and nonessential amino acids, indicating that these strand breaks were poorly repaired. Cell death commenced after 10 hr of incubation with methotrexate and continued during the following 3-4 days. These findings suggest that cell death was due to a lethal accumulation of DNA strand breaks. The formation of DNA strand breaks is probably due to inefficient DNA repair, resulting from the inhibition of syntheses of thymidylate and of purine nucleotides. The accumulation of DNA strand breaks was minimal in growth-arrested cells, which are resistant to methotrexate toxicity.

Animals↗

PubMedDate not supplied

Exposure of oncologic nurses to methotrexate in the treatment of osteosarcoma.

Methotrexate is a therapeutic agent used widely for osteosarcoma. We used an extremely sensitive high-performance liquid-chromatography assay to evaluate 112 urine samples obtained from 28 hospital employees during high-dose therapy with methotrexate and during routine care of patients. The highest cumulative urinary excretion was observed when methotrexate infusions were handled in a workbench from which a portion of filtered air was emitted into the room. Remarkable urine contaminations were identified for personnel, including 1 administrative employee who had "stood by" for 2 h in the room where infusions were prepared. Lower methotrexate concentrations were detected in the urine of nurses whose exclusive function was to care for patients. The urine burden in oncologic nurses decreased after a central pharmacy unit was installed. Methotrexate was excreted in the sweat of patients who were under high-dose therapy, and its elimination half-life was 11.1 h (mean maximal concentration = 1.7 micrograms/ml [n = 51). The maximal burden in spontaneous vomit from these patients was 441.5 micrograms/ml, and it declined to 0.24 micrograms/ml 19.5 h after infusion was completed. No methotrexate was detected in personnel who prepared 20-g methotrexate infusions in the central pharmacy unit. We demonstrated that occupational safety depended not only on technical precautions, but on the skills of specifically trained personnel.

Antimetabolites, Antineoplastic↗

PubMed2003

Methotrexate stimulates lung epithelial cells to release inflammatory cell chemotactic activities.

Methotrexate-induced pneumonitis has been reported as an infrequent but potentially serious complication of therapy in a variety of malignant and benign conditions. Because inflammatory cell infiltration is concerned with the development of methotrexate-induced pneumoinitis, and because airway epithelial cells participate in the orchestration of lung inflammation, the authors determined whether methotrexate might stimulate airway epithelial cells (A549 cells) to release neutrophil, monocyte, and eosinophil chemotactic activities (NCA, MCA, and ECA). A549 cells released NCA, MCA, and ECA in a dose- and time-dependent manner in response to methotrexate. Partial characterization revealed the heterogeneity of NCA, MCA, and ECA. The release of chemotactic activity was blocked by lipoxygenase inhibitors and cycloheximide. NCA was inhibited by leukotriene (LT) B(4) receptor antagonist, and anti-interleukin (IL)-8 and granulocyte colony-stimulating factor (G-CSF) antibodies. MCA was attenuated by LTB(4) receptor antagonist, and anti-monocyte chemoattractant protein (MCP)-1 and granulocyte-macrophage CSF (GM-CSF) antibodies. ECA was attenuated by LTB(4) receptor antagonist, and anti-IL-8 and GM-CSF antibodies. The release of IL-8, G-CSF, MCP-1, GM-CSF, and LTB(4) from A549 cells significantly increased in response to methotrexate. The mRNA expression of IL-8 and MCP-1 was augmented by methotrexate stimulation. These data suggest that type II epithelial cells may modulate inflammatory cell recruitment into the lung by releasing NCA, MCA, and ECA in response to methotrexate.

Antibodies, Blocking↗

PubMed1998

Induction by estrogens of methotrexate resistance in MCF-7 breast cancer cells.

Development of drug resistance is a major factor that limits the effectiveness of chemotherapy treatments. In this study, we determined whether estradiol or its metabolites 2-, 4- and 16alpha-hydroxyestrone could enhance the development of methotrexate resistance in the breast carcinoma cell line, MCF-7. Cells were incubated with the estrogens at a concentration of 10(-8) M for 12 cell doublings and enhancement of methotrexate resistance was measured with the Luria-Delbrück assay. The most efficient estrogens were the 4-hydroxyestrone and 16alpha-hydroxyestrone, which both stimulated methotrexate resistance by 88-fold as compared with the control without estrogen. 2-Hydroxyestrone had an enhancement factor of 33-fold, whereas estradiol showed a slight effect with an enhancement factor of 3.2-fold. To determine whether the estrogen receptor was involved in the development of resistance, expression of the pS2 gene, which contains an estrogen-responsive element, was measured. Both estradiol and 16alpha-hydroxyestrone stimulated expression of the pS2 gene. In contrast, 2- and 4-hydroxyestrone did not increase the level of pS2 mRNA. This suggests that tumors classified as estrogen receptor negative could also develop methotrexate resistance as the result of exposure to estrogens. The status of the tumor suppressor gene p53 was analyzed in methotrexate sensitive and resistant clones. In all the methotrexate resistant clones analyzed, the western blots indicated that the p53 protein was still present and transcriptionally competent, as measured by its capacity to stimulate transcription of the p21waf1/cip1 gene following UVB irradiation. However, the basal level of p53 was higher in resistant clones and addition of 2- or 4-hydroxyestrone increased p53 to levels equivalent to those observed following UVB irradiation. However, this induction of p53 accumulation by estrogens failed to stimulate the transcription of p21waf1/cip1, which indicates that a transcriptionally inactive form of p53 accumulated in methotrexate resistant cells.

Antimetabolites, Antineoplastic↗

PubMed1997

Effect of methotrexate and sulphasalazine on UMR 106 rat osteosarcoma cells.

Methotrexate is commonly used in the treatment of rheumatoid arthritis. An osteopathy has been described in children treated with methotrexate for leukaemia, consisting of bone pain, osteoporosis and fractures. Animals given short-term high-dose and long-term low-dose methotrexate have both reduced bone formation and increased resorption on histomorphometry. As patients with rheumatic diseases have numerous risk factors for osteoporosis, possible additional risk from low-dose methotrexate is of relevance to the rheumatologist. To investigate further the mechanism of osteoporosis in animals and man, in vitro studies were carried out on an osteoblast cell line, using concentrations found in patients with rheumatic disease. UMR 106 rat osteoblast-like osteosarcoma cells were incubated with methotrexate, and also with sulphasalazine, an anti-rheumatic drug with no known effect on bone, for comparison. A dose-dependent toxic effect of methotrexate on the cell line was observed using concentrations found in patients with rheumatic disease. This was not observed with sulphasalazine. The reduced bone formation observed in animals and man may be due to a direct effect of methotrexate on the osteoblast.

Alkaline Phosphatase↗

PubMed1993

Pharmacokinetic interaction between high-dose methotrexate and amoxycillin.

A case report of toxicity following concurrent administration of high-dose methotrexate and amoxycillin is presented. A 16-year-old male patient was administered 10 high-dose methotrexate cycles for treatment of a fully malignant osteogenic sarcoma. Methotrexate was administered at a dosage of 8 g/m2 and infused intravenously over a 6-h period. The patient received pre- and posttreatment hydration and sodium bicarbonate for alkalinization of urine. Calcium folinate rescue was performed when appropriate. During the 10th cycle, coadministration of amoxycillin (1 g/6 h, p.o.) resulted in prolonged and marked enhancement of methotrexate serum levels. Pharmacokinetic parameters obtained in cycle 10 indicate significant differences for total plasma clearance, mean residence time, and distribution half-life when compared to those in cycles 1-9. Amoxycillin decreased the renal clearance of methotrexate, probably by competition at the common tubular secretion system and by secondary methotrexate-induced renal impairment. The patient experienced acute and subacute toxicity with renal failure, myelosuppression, mucositis, nausea, vomiting, fever, and dermatologic abnormalities. Patients receiving amoxycillin during methotrexate therapy should be closely monitored to avoid severe toxicity.

Adolescent↗

PubMed1999

Methotrexate in refractory Crohn's disease.

BACKGROUND: Recent trials suggested that methotrexate may be effective in refractory Crohn's disease (CD). We analyzed the data of 20 patients treated with methotrexate because of corticodependent or refractory CD. METHODS: Between January 1995 and June 1997, 20 azathioprine-resistant or -intolerant patients with active CD requiring continuous glucocorticosteroid treatment were treated with parenteral methotrexate. Clinical response was assessed by the Harvey-Bradshaw clinical activity index. Concomitant steroid use and steroid withdrawal rates were recorded. Patients were assessed at 12 weeks, 6 months, 9 months, and 12 months after the start of methotrexate therapy. RESULTS: At 12 weeks, a clinical response was obtained in 14/20 patients (70%). These response rates decreased to 10/20 patients at 6 months, 8/17 patients at 9 months, and 4/14 evaluable patients at 12 months. In initial responders (n = 14), maintenance of remission was observed in 9/14, 6/11, and 3/9 patients at 6, 9, and 12 months, respectively. Methotrexate allowed corticosteroid tapering in 85% of patients and discontinuation in 60% of patients at 6 months. Side effects were rather frequent but usually mild and prompted discontinuation in two patients. CONCLUSIONS: In this retrospective study, parenteral methotrexate appeared to be effective in inducing a clinical response in 70% of azathioprine-resistant or -intolerant CD patients and often permitted corticosteroid tapering, with an acceptable short-term toxicity. The potential of methotrexate to maintain long-term remission in refractory patients, however, appears less convincing.

Adolescent↗