Cumulative Dose Of Methotrexate Research Articles

Neuromuscular impairments in adult survivors of childhood acute lymphoblastic leukemia: associations with physical performance and chemotherapy doses.

Treatment regimens for childhood acute lymphoblastic leukemia (ALL) contain neurotoxic agents that may interfere with neuromuscular health. In this study, the authors examined associations between neuromuscular impairments and physical function and between neuromuscular impairments and doses of vincristine and intrathecal methotrexate used to treat leukemia among survivors of childhood ALL. ALL survivors >10 years from diagnosis participated in neuromuscular performance testing. Treatment data were abstracted from medical records. Regression models were used to evaluate associations between treatment factors, neuromuscular impairments, and physical performance. Among 415 survivors (median age, 35 years; age range, 21-52 years), balance, mobility, and 6-minute walk (6MW) distances were 1.3 standard deviations below age-specific and sex-specific values in 15.4%, 3.6%, and 46.5% of participants, respectively. Impairments included absent Achilles tendon reflexes (39.5%), active dorsiflexion range of motion (ROM) <5 degrees (33.5%), and impaired knee extension strength (30.1%). In adjusted models (including cranial radiation), survivors who received cumulative intrathecal methotrexate doses ≥215 mg/m(2) were 3.4 times more likely (95% confidence interval, 1.2-9.8 times more likely) to have impaired ROM than survivors who received no intrathecal methotrexate, and survivors who received cumulative vincristine doses ≥39 mg/m(2) were 1.5 times more likely (95% CI, 1.0-2.5 times more likely) to have impaired ROM than survivors who received lower cumulative doses of vincristine. Higher intrathecal methotrexate doses were associated with reduced knee extension strength and 6MW distances. Neuromuscular impairments were prevalent in childhood ALL survivors and interfered with physical performance. Higher cumulative doses of vincristine and/or intrathecal methotrexate were associated with long-term neuromuscular impairments, which have implications on future function as these survivors age.

Evaluation of liver fibrosis by transient elastography in methotrexate treated patients

Methotrexate (MTX) safety is questioned by the risk of inducing liver fibrosis (LF). As transient elastography (FibroScan®) is an effective non-invasive technique to evaluate LF, our aims were to assess LF in MTX-treated patients, to evaluate LF regarding treatment duration and cumulative dose, and to determine differences depending on the underlying disease. Prospective study including patients with rheumatoid arthritis, inflammatory bowel disease, and psoriasis treated with MTX. Hepatic stiffness was determined by FibroScan®. The LF cut-off values were established using METAVIR score. Of 53 patients, 22 were men (41.5%), mean age was 55 (15) years, 17 (32%) had rheumatoid arthritis, 18 (34%) inflammatory bowel disease, and 18 (34%) psoriasis. Mean MTX cumulative dose was 1,805 (1,560) mg, and mean treatment duration was 178 weeks. Mean hepatic stiffness was 6.19 (2.43) KPa. In 49 patients (92.5%), absence/mild LF was found (F ≤ 2), and 4 patients (7.5%) had advanced LF (F ≥ 3). Treatment duration or cumulative doses of MTX were not associated with LF. Regarding LF development, MTX therapy is safe. FibroScan® is useful for monitoring LF in MTX-treated patients.

Different outcome in older children with acute lymphoblastic leukemia with different treatment protocols in the Netherlands

From 1991 until 2004 children with acute lymphoblastic leukemia (ALL) in the Netherlands were treated according to protocols ALL-8 and ALL-9 which were based on different principles. An earlier study showed that the outcome of adolescents highly differed on these protocols. In this retrospective study, we analyzed whether the outcome of older children 10-15 years of age at diagnosis differed between the Berlin-Frankfurt-Münster (BFM)-based ALL-8 regimen and the ALL-9 regimen. Two hundred fifty-four older children who were treated according to protocol ALL-8 (n = 82) or ALL-9 (n = 172) were included in the analysis. A higher 5-year event-free survival (EFS) rate was found for patients treated according to ALL-8 compared to ALL-9 (79 ± 5% vs. 65 ± 4%, P = 0.02). Patient characteristics did not differ except for a slightly higher age in ALL-8. Therefore, additional analyses were done including only patients who were 12-15 years of age. In this age group there was also a difference in the 5-year EFS (82 ± 5% vs. 61 ± 5%, P = 0.00) as well as in the 5-year overall survival rate; 89 ± 4% compared to 68 ± 5%, respectively (P = 0.01). Major difference between protocols was the use of a consolidation and reinduction/intensification course and higher cumulative doses of asparaginase, methotrexate, and anthracyclines in ALL-8. Children 10-15 years of age have been undertreated with the ALL-9 regimen and benefit by intensive treatment components as used in ALL-8. We recommend using BFM-based protocols for these older children with ALL.

A Review of the Efficacy and Safety of Combined Methotrexate and Ultraviolet B Phototherapy versus Ultraviolet B Phototherapy Alone in the Treatment of Psoriasis

Background Methotrexate (MTX) and ultraviolet light B (UVB) phototherapy are effective as single agents for psoriasis. By combining the two agents, it is proposed that the use of UVB-MTX can yield greater therapeutic efficacy than using MTX or UVB alone and limit the cumulative exposure of both UVB and MTX to the patient. Objective To review evidence on the clinical efficacy and safety of using combined UVB-MTX compared with using UVB alone. Methods We performed a PubMed search for studies involving the combination of UV therapy with MTX. The reported studies evaluate the clinical efficacy and safety of UVB-MTX therapy compared with UVB alone. Results Based on the studies we reviewed, combined UVB-MTX therapy is more effective than UVB alone in treating psoriasis. The mean cumulative MTX doses ranged from 112 to 196 mg, and no cases of MTX-related liver toxicity symptoms were reported in the three studies. Discussion Combination phototherapy involving UVB-MTX is more clinically effective than UVB alone for patients with plaque-type psoriasis. The current review is limited by the absence of studies comparing the efficacy of combined UVB-MTX therapy with MTX monotherapy. Combination UVB-MTX therapy appears to be safe and well tolerated.

Évaluation à long terme de l’efficacité du méthotrexate seul ou associé à de faibles doses de corticoïdes dans le traitement des pelades décalvantes totales

Treatment of severe and chronic forms of alopecia areata (AA) totalis remains difficult. It has been suggested that methotrexate (MTX) is an efficacious treatment for AA totalis. The aim of our study was to assess the long-term safety and efficacy of MTX in patients with chronic severe forms of AA totalis. Thirty-three patients (24 women and nine men) with AA totalis or universalis were included. Mean disease duration was 7.7 years and these patients had not responded to prior standard treatment. The initial weekly dosage of MTX was 15 mg (n=2), 20mg (n=16) or 25mg (n=15). Nineteen patients (58%) were treated with MTX and low doses of corticosteroids (prednisone 10-20mg/d), while 14 patients (42%) received MTX alone. The primary end-point was complete hair regrowth under treatment. Twenty-one patients had total hair regrowth and 13 patients were considered as treatment failures, with 10 of these having partial regrowth and three having no regrowth. Complete regrowth was seen in 12 of 19 patients (63%) on combined treatment and in eight of 14 patients (57%) on MTX alone. The onset of hair regrowth was noted after a median delay of 3 months. At the end of the study, after a median of 30 months' follow-up, the median cumulative dose of MTX was 1.8 g (400mg-5.5 g). Relapse was observed on corticosteroid dose reduction or withdrawal in 16 of the 20 patients in whom total hair regrowth initially occurred. Regrowth after treatment of relapse was seen in 14 of these 16 patients (87%). Seven patients experienced adverse events consisting of transient elevated transaminases (n=4), persistent nausea (n=2) and lymphocytopenia (n=1). MTX alone or in combination with low doses of oral corticosteroids resulted in complete hair regrowth in about half of these patients presenting AA totalis or universalis. Lasting improvement required continuous treatment in most cases.

Assessment of liver fibrosis by transient elastography in rheumatoid arthritis patients treated with methotrexate

ObjectiveThis study was designed to assess the degree of liver fibrosis with transient elastography and noninvasive biochemical methods in rheumatoid arthritis patients treated with methotrexate. MethodsWe reviewed the medical records of rheumatoid arthritis patients who were administered methotrexate for more than 3 years. Transient elastography was performed and serological markers of liver fibrosis were evaluated by prospectively and was compared with the result of healthy control group. A correlation of the cumulative dose of methotrexate with the elastography value (kPa) or the level of serological markers was assessed. Two subgroups of patients were compared; patients who received a cumulative dose of methotrexate of less than 4000mg (group 1) and more than 4000mg (group 2). A total of 177 consecutive rheumatoid arthritis patients were evaluated. ResultsThe mean cumulative dose of methotrexate was 3988±1566mg with doses ranging from 652.5 to 10,415mg. The mean elastography value of all patients was 4.01±0.77kPa. The kilopascal values and levels of biochemical markers did not correlate with the cumulative dose of methotrexate, but did correlate with the AST to ALT ratio, AST to platelet ratio index, haptoglobin level. Mean kilopascal values were not statistically different for group 1 and group 2 patients. For rheumatoid arthritis patients treated with a high cumulative dose of methotrexate, significant liver fibrosis is rare and is not accurately detected in patients with liver enzyme abnormalities. ConclusionTaking into account the risk and benefit of a liver biopsy, transient elastography can be recommended as an additional diagnostic option.

PTU-053 Is procollagen III aminopeptide a good predictor of liver fibrosis in patients with psoriasis on methotrexate therapy?

<h3>Introduction</h3> The prevalence of hepatotoxicity in long-term methotrexate therapy is around 0–4%. The British Association of Dermatology recommends procollagen III aminopeptide (PIIINP) level monitoring to identify patients at risk of hepatotoxicity with a view to liver biopsy while North American guidelines recommend liver biopsy based on cumulative dose of methotrexate. <h3>Methods</h3> 1. To correlate the accuracy of abnormal PIIINP level to predict liver fibrosis in patients receiving long-term methotrexate for psoriasis. 2. To assess adherence to the British Association of Dermatology guidance for PIIINP monitoring. The histology database (SNOMED) was interrogated for a 5-year period (1 January 2003 to 31 December 2007) to find all patients whose liver biopsies had been reported to show fibrosis, and patients with psoriasis identified. Case notes were reviewed for all psoriasis patients on long-term methotrexate. Levels of PIIINP, cumulative methotrexate dosage, comorbidities, drug history, alcohol intake, liver histology and clinical decision following liver biopsy (continuation or stoppage of methotrexate) were recorded. <h3>Results</h3> 578 liver biopsies during this period yielded 38 patients receiving methotrexate. 7 patients had methotrexate for another condition and were excluded; a further nine were excluded due to lack of case notes or repeat biopsies for follow-up. 22 patients with psoriasis had liver biopsies while on methotrexate treatment, of which 18 had elevated PIIINP levels above recommended threshold for liver biopsy and four patients had clinician decided biopsies. The mean cumulative dose of methotrexate to first biopsy was 3.86 g (range 0.69 g–9.25 g). The mean time to first biopsy was 4.2 years (range 1.1–10.1 years). 2 patients had PIIINP levels above 8 μg/l, one of which had grade 2 fibrosis on biopsy; the remaining 16 had PIIINP between 4.2 and 8 μg/l and two had Grade 2 fibrosis in this group. Liver histology (n=21): 15 patients had steatosis, three patients had grade 2 and one patient had Grade 1 fibrosis and two patients had normal liver histology. Clinical Outcome: four patients with fibrosis had methotrexate stopped as a result of the biopsy findings and the rest were continued (80%). <h3>Conclusion</h3> 19/21 (90%) patients with abnormal PIIINP had abnormal liver histology, but only 19% had fibrosis sufficient to discontinue treatment. PIIINP therefore did not correlate well with liver fibrosis. Newer non-invasive methods such as Fibroscan® may assess fibrosis better in this group of patients and need to be studied.

Changes in Liver Biochemistry During Methotrexate Use for Inflammatory Bowel Disease

We aimed to characterize the spectrum of liver enzyme test (LET) abnormalities that occur while using methotrexate for inflammatory bowel disease (IBD). A retrospective review was undertaken of subjects using methotrexate for IBD at a single center. The clinical and epidemiological parameters, and hepatotoxicity risk factors, were recorded. Subjects were excluded if cumulative methotrexate doses could not be ascertained, if they had a diagnosis of rheumatoid arthritis or psoriasis, or if baseline and follow-up LETs were not available. Also noted were the cumulative methotrexate dose during the peak LET increase, severity of LET increase, and whether normalization occurred. Eighty-seven subjects were included (Crohn's disease, n=67; UC, n=17; indeterminate colitis n=3). The mean therapy duration was 81 weeks (3- to 364-week range), and the cumulative average dose was 1,813 mg (25-8,255-mg range). Thirty-seven (43%) subjects received a cumulative dose >1,500 mg. Sixty-seven (77%) had normal LETs, and in 51 (76%) LETs remained normal throughout methotrexate therapy. In the 16 (24%) who developed LET abnormalities, seven (44%) had underlying risk factor(s) for liver disease. Normalization (without dose reduction) occurred in 14 (88%) while continuing methotrexate. Of 20 subjects with abnormal LETs at baseline, nine (45%) subsequently normalized while continuing methotrexate, whereas nine (45%) worsened. Seventeen liver biopsies were performed in 11 and were classified as Roenigk's grade I in 15 (88%) subjects. Roenigk IIIb or IV was not seen. Methotrexate is commonly associated with LET abnormalities, but these frequently normalize while still on therapy, and in only 5% will drug discontinuation be necessary. Liver biopsies rarely have substantive abnormalities.

Methotrexate for maintenance of remission in chronic active Crohnʼs disease

According to current guidelines methotrexate (MTX) should be considered as a second-line immunomodulator in patients with chronic active Crohn's disease (CD) if purine analogs are not tolerated or there is a lack of efficacy. However, its therapeutic role remains controversial to the present day. Medical records of all eligible patients treated in the outpatient clinic of the Johann Wolfgang Goethe-University Hospital between December 2000 and January 2009 were reviewed. Sixty-three patients were identified. The mean duration of treatment was 100 weeks (range, 2-364 weeks) with a mean cumulative dose of MTX of 2130 mg (range, 40-9005 mg). In 50 (79%) patients started on MTX clinical remission could be achieved within 3 months of treatment. The cumulative probability of these patients to maintain remission was 95.3%, 89.5%, 70.6%, and 62.8% at 6 months, 1, 2, and 3 years of treatment, respectively. The respective figures of the meta-analysis were 94%, 86%, 75%, 53%, and 43. Drug-related side effects were reported in 50 patients (79%), leading to withdrawal of MTX in 21 cases (33%). Along with previous observations our data demonstrate the efficacy of MTX as a second-line immunomodulator in chronic active CD. However, its use is limited due to intolerable side effects in a large proportion of patients. The results should encourage further research in order to establish the definite significance of MTX in chronic active CD.

THE SAFETY OF INTRAOCULAR METHOTREXATE IN SILICONE-FILLED EYES

Intraocular methotrexate has been safely used in eyes with primary CNS lymphoma (PCNSL), and in eyes with uveitis and proliferative diabetic retinopathy. Dosing in silicone-filled eyes was reduced from a standard 400 microg intravitreal injection due to concerns of toxicity. The present study reports the visual results of non-PCNSL, silicone-filled eyes treated with intravitreal methotrexate using cumulative dosages ranging from 200 microg to 1,200 microg. In this retrospective case series, all patients with silicone-filled eyes who received intraocular methotrexate were included. Patients were observed with serial ophthalmic examinations. Best-corrected visual acuity was measured by Snellen acuity. Pretreatment acuities were compared to those obtained at last follow-up. The cohort included 12 patients (13 eyes) with disease other than PCNSL. The cumulative dose of intraocular methotrexate in any one patient ranged from 200 microg to 1,200 microg. Mean follow-up was 9 months (median, 10 months; range, 2 weeks to 16 months). Best-corrected vision at last follow-up was either stable or improved from pretreatment acuity in 12 of 13 eyes. Preservation of acuity in 12 of 13 study eyes suggests that intravitreal methotrexate in a cumulative dose of up to 1,200 microg is safe in silicone-filled eyes.

Long-term Methotrexate for Crohn's Disease

To assess the efficacy and safety profile of methotrexate (MTX) for the treatment of Crohn's disease (CD) in clinical practice. MTX is widely used for some chronic immunologic diseases. Although some randomized controlled trials suggest its efficacy in CD, this drug remains a second-line, underused, immunomodulator. Medical records of all patients treated with MTX for CD in our center (n=44) were reviewed. Clinical and epidemiologic parameters, including risk factors for hepatotoxicity, were registered. MTX was prescribed mainly for steroid-dependency (n=22) and as concomitant treatment to infliximab (n=18). Mean duration of treatment was 22.9+/-19 months, with a mean cumulative dose of MTX of 1169+/-784 mg. Thirty-nine percent of patients developed drug-related side effects, hepatotoxicity being the most frequent [13 patients (30%)]. However, only 5 patients (11%) had to discontinue MTX. In steroid-dependent CD patients, disease remission and complete steroid withdrawal was achieved in 77% of cases. Seven patients lost their initial response to MTX during follow-up, leading to a cumulative probability of remission of 39% after 3 years of treatment. MTX is well tolerated in most CD patients. Although a great proportion of steroid-dependent CD patients achieve disease remission and steroid withdrawal, there is a trend to a loss of efficacy with time. Larger, long-term studies are necessary to establish the role of MTX in the management of CD.

Systemic Methotrexate Treatment in Childhood Psoriasis: Further Experience in 24 Children from India

Well-designed studies on systemic therapeutic modalities for severe psoriasis in children are rare. Children with severe disease are treated with the support of data extrapolated from that in adult, although management in them differs from adults in several important aspects. Like other systemic modalities, data regarding the use of methotrexate in the treatment of childhood psoriasis is meager. This study aims to analyze the efficacy and safety of methotrexate in severe or disabling childhood psoriasis. The records of all the patients <18 years of age treated with systemic methotrexate at the psoriasis clinic of our institute from January 1993 to December 2006 were retrieved. Information regarding demographic profile, disease characteristics, response to treatment, side effects, etc. was noted from predesigned clinic proforma. Indications of methotrexate use were baseline psoriasis area and severity index (PASI) >10, disease refractory to conventional therapies and disabling psoriasis even though the psoriasis area and severity index was <10. Clinical status of patients was assessed at weekly intervals for the first 2 weeks, fortnightly during next month and then monthly. Response to therapy was graded as good (50-75% decrease in PASI) and excellent (>75% decrease in PASI). Laboratory investigations to detect methotrexate induced toxicity were performed at regular intervals. Of the 29 patients treated with methotrexate, 24 were eligible for the final data analysis. Indication for the institution of methotrexate therapy was severe disease, viz., extensive recalcitrant plaque type psoriasis in 17 patients, erythroderma and generalized pustular psoriasis of von-Zumbusch type in three patients each and severe disabling palmo-plantar involvement along with chronic plaque lesions in one patient. Response to therapy was excellent (>75% decrease in PASI) in all but two patients. The mean time to control the disease, i.e., 50% reduction in PASI was 5.1 weeks. Mean total cumulative dose of methotrexate in the first episode was 215 mg. The duration of remission could be calculated in nine patients only, varying from 1.5 months to 3 years. Side effects were mild, observed in nine children, which included nausea, vomiting, and loss of appetite. Methotrexate is an effective, cheap, easily available, and reasonably safe drug to be used in severe childhood psoriasis under an expert supervision and laboratory monitoring.

Hodgkin's lymphoma in a patient of psoriasis treated with long-term, low-dose methotrexate therapy

Methotrexate (MTX) is used in the treatment of a variety of diseases such as rheumatoid arthritis, dermatomyositis, juvenile rheumatoid arthritis and chronic plaque psoriasis. It has been well documented that there is a risk of development of lymphomas in these patients although none have been reported in patients of psoriasis treated with methotrexate. A 58-year-old male patient, a known case of psoriasis since 1994, had been receiving treatment with a low dose of MTX, 5 mg weekly for ten years intermittently (7-8 months/year). The cumulative dose of MTX taken was 1.5 gm. He developed high-grade fever with cervical lymphadenopathy that was nonresponsive to routine line of management. Lymph node biopsy revealed the presence of mixed cellularity type of Hodgkin's lymphoma. CT scan showed cervical, mediastinal and abdominal lymphadenopathy. The patient responded well to withdrawal of MTX and chemotherapy. This is the first case of lymphoma occurring in a patient of psoriasis treated with low-dose MTX.

Análisis del resultado de pruebas hepáticas en pacientes psoriáticos tratados con metotrexato: Estudio retrospectivo

Methotrexate is one of the best systemic treatments for psoriasis. However it has significant adverse effects such as myelotoxicity and hepatotoxicity. To evaluate serum liver test in psoriatic patients treated with methotrexate. Retrospective review of medical records of psoriatic patients treated with methotrexate between the years 2000 and 2005. All patients received a minimum of 7.5 mg weekly of methotrexate, for at least 4 weeks. Sixty three patients were included. Mean cumulative dose of methotrexate was 576 mg. Thirty two percent had alterations in liver tests, but only 9% had values that duplicated the upper limit of normal range of aminotransferases or alkaline phosphatases or a serum bilirubin over 2 mg/dl. We did not find a direct relationship between the dose of methotrexate and the magnitude of liver test alterations. Only one patient exceeded 1.5 g as cumulative dose. A liver biopsy performed to him, did not show signs of fibrosis. This retrospective study does not show a direct relationship between weekly doses, cumulated dose and length of treatment with methotrexate, and the degree of alteration of serum liver tests.

Psoriasis patients with diabetes type 2 are at high risk of developing liver fibrosis during methotrexate treatment

We investigated the impact of diabetes mellitus type 2, overweight, alcohol over-consumption, and chronic hepatitis B or C as risk factors, for liver fibrosis in psoriasis patients treated with methotrexate. One hundred and sixty-nine liver biopsies from 71 patients who underwent liver biopsies as part of the monitoring of methotrexate treatment for psoriasis were reviewed. Fibrosis, steatosis and inflammation were staged according to the NAFLD activity score. Twenty-six patients had one or more of the risk factors and 25 (96%) of these (median cumulative dose methotrexate 1500 mg) developed liver fibrosis. Of those without risk factor, 26 (58%) (p=0.012) developed fibrosis (median cumulative dose methotrexate 2100 mg). Ten (38%) of the patients with risk factor(s) had severe fibrosis (stage 3-4) (mean cumulative dose methotrexate 1600 mg), while four (9%) (p=0.0012) of those without risk factors had severe fibrosis (median cumulative dose methotrexate 1900 mg). Patients with methotrexate treated psoriasis and risk factors for liver disease, especially diabetes type 2 or overweight, are at higher risk of developing severe liver fibrosis compared to those without such risk factors, even when lower cumulative methotrexate doses are given.

Liver injury in long‐term methotrexate treatment in psoriasis is relatively infrequent

Methotrexate-induced liver damage in psoriasis has led to dermatologic guidelines that stipulate monitoring of liver injury by means of serial liver biopsies. Recent literature data suggest that methotrexate may be considerably less hepatotoxic than previously assumed. To evaluate prevalence and development of liver injury in methotrexate treated psoriasis. Retrospective chart review (1976-2005). Hundred and twenty-five patients (F58/M67; mean age 45.0, SD 12.7 years) received a median cumulative methotrexate dose of 2,113 mg (range 180-20 235) over a median period of 228 weeks (range 16-1763). Two hundred and seventy eight liver biopsies were analysed and 71% were classified as Roenigk grade I, 14% as Roenigk II, 14% grade IIIa, 2% grade IIIB and 2% grade IV. Liver injury was not associated with cumulative dose, weekly prescribed dose, age or duration of treatment. Obesity and diabetes were significant risk factors for liver injury. A total of 68 patients had multiple biopsies, 3% improved, 72% did not change and in 25% liver histology deteriorated. The majority of cases (84%) that progressed to Roenigk 2 had a cumulative dose of 1,500-6,000 mg. Methotrexate-related liver injury is less frequent than previously thought and mostly occurred at cumulative dose of <6,000 mg. Diabetes and being overweight are significantly correlated with liver injury.

Sequential liver biopsies during long-term methotrexate treatment for psoriasis: a reappraisal.

One hundred and eighty-two liver biopsies were performed over a 10-year period on patients receiving long-term, low-dose, once weekly oral methotrexate (MTX) for severe psoriasis. Forty-nine patients had two or more biopsies during continued treatment and formed the study population for our analysis. The first and last biopsies were compared to determine progression of any histological abnormalities. Liver biopsies were assessed without knowledge of the MTX dose and allocated to one of five groups according to the severity of the histological abnormalities. These were defined as: (1) normal; (2) steatosis alone; (3) inflammation without fibrosis; (4) fibrosis; and (5) cirrhosis. The mean cumulative dose of MTX at the time of the first biopsy was 2743 mg (range 315-10,024), given over 275 weeks (range 26-738). In the interval between the first and last biopsies, patients received, on average, a further 2362 mg (range 390-7155) over 225 weeks (range 60-460). There was improvement in the histological assessment in 12 patients, no change in 28 patients, and deterioration in nine patients. None developed cirrhosis. Liver biopsy findings prompted discontinuation of MTX in four of the 49 patients on long-term treatment. This has to be weighed against the cost and morbidity of the 124 biopsies performed in these patients. Our results suggest that, with careful follow-up, the risk of development or progression of liver disease in patients receiving long-term, low-dose, once weekly oral MTX for psoriasis is modest, and that the requirement for performing routine liver biopsies in these patients needs to be reconsidered.

Methotrexate and ciclosporin combination for the treatment of severe psoriasis

Psoriasis is a chronic skin disease that often requires long-term therapy to control the symptoms. Combination therapies for severe psoriasis have advantages for disease control and are thought to reduce long-term side-effects. To assess the efficacy and side-effects of methotrexate plus ciclosporin used in combination for the treatment of severe psoriasis. In this prospective study, 20 patients were treated with the combination of methotrexate and ciclosporin. Methotrexate was given intramuscularly as a single weekly dose of 10 mg and ciclosporin at a dose of 3.5 mg/kg/day in two equally divided doses. Clinical response was assessed according to clinical outcome and the Psoriasis Area and Severity Index which were evaluated at the beginning of therapy (PASI1), after cessation of one agent (PASI2), and at the end of therapy (PASI3). All the patients had previously received one or more systemic treatment. There were 10 women and 10 men (mean age 44 years). The median (minimum to maximum) duration of methotrexate and ciclosporin treatments were 12.5 (4-55) and 14.0 (4-80) weeks, respectively. Median duration of combination therapy was 9.5 weeks (range 4-50). The median of previously used and end-of-study cumulative doses of methotrexate were 181.8 mg (range 0-785) and 330.8 mg (range 50-845), respectively. The median PASI scores were decreased by 77.4% (range 51.2-90.2) and 75.9% (range 10.1-100) at PASI2 and PASI3, respectively. Patients with severe psoriasis had clinically significant improvement after the initiation of combination therapy. Healing rate was decreased upon cessation of one of the medications. Short-term side-effects were minor, transient and manageable. Long-term follow-up of patients treated with this combination is needed.

Diagnosis of liver fibrosis by transient elastography (FibroScan) and non‐invasive methods in Crohn's disease patients treated with methotrexate

Methotrexate is an effective treatment in Crohn's disease, which may induce liver fibrosis with high cumulative doses. Transient elastography (FibroScan, Echosens, Paris, France) is a new non-invasive rapid, allowing assessment of liver fibrosis by measurement of liver stiffness. A prospective study to evaluate liver fibrosis with FibroScan and non-invasive biochemical methods in Crohn's disease patients treated with methotrexate. Consecutive Crohn's disease patients had evaluation of liver fibrosis with non-invasive methods. Two subgroups of patients were compared: cumulative dose of methotrexate of more than 1500 mg (group 1) and naive for methotrexate (group 2). Liver biopsy was performed in patients with persistent liver enzyme abnormalities or FibroScan value >8.7 kPa. Fifty-four consecutive Crohn's disease patients were fully investigated (45 females, mean age 41 +/- 14 years). Median FibroScan values were similar in group 1 (n = 21) and in group 2 (n = 33), 5.5 and 4.5 kPa, respectively. FibroScan values were not correlated with the cumulative dose of methotrexate. In Crohn's disease patients treated with a high dose of methotrexate, significant liver fibrosis is rare and not accurately detected with liver enzymes abnormalities. FibroScan could be recommended and liver biopsy could be performed only with patients with high values and/or with chronic liver enzymes abnormalities.

Decrease in motor performance in children with cancer is independent of the cumulative dose of vincristine

Impaired performance on motor tasks in children treated for acute lymphoblastic leukemia (ALL) after completion of treatment is often attributed to vincristine (VCR). Whether motor problems persist in other children who receive different cumulative doses of VCR is to the authors' knowledge not known. The objective of the current study was to determine the extent of motor problems in children with ALL, Wilms tumor (WT), B-cell non-Hodgkin lymphoma (B-NHL), and malignant mesenchymal tumors (MMT) and whether these motor problems were related to VCR dose. In 128 children ages 4-12 years who completed treatment after at least 1 year, motor performance was measured using the Movement Assessment Battery for Children (m-ABC). The m-ABC scores of the total study group were significantly lower than those of the normal population (P < 0.001). There were no differences in scores noted between children with ALL, WT, B-NHL, or MMT. There also were no differences noted between those children with ALL who had received pulses of VCR and steroids during maintenance therapy and those who had not. All groups demonstrated large variability in scores. Scores were not found to be significantly different between those children who had received low (< 20 mg/m(2)), intermediate (20-40 mg/m(2)), or high (> 40 mg/m(2)) cumulative doses of VCR. Cumulative doses of corticosteroids and methotrexate did not affect scores, nor did age at diagnosis and time since the completion of therapy. Although motor performance was impaired in all patient groups, no correlation was found between motor performance and the cumulative dose of VCR or other drugs, age, and follow-up time. Future studies have to address several issues, including whether polymorphisms in drug metabolizing genes or drug target genes explain the significant variability noted in the long-term motor outcome of children with cancer.