Randomised trial of oral and intravenous methylprednisolone in acute relapses of multiple sclerosis. A randomised controlled trial comparing rehabilitation against standard therapy in multiple sclerosis patients receiving intravenous steroid treatment. Methylprednisolone in multiple sclerosis: a comparison of oral with intravenous therapy at equivalent high dose. A placebo-controlled, randomized, double-masked, variable dosage, clinical trial of azathioprine with and without methylprednisolone in multiple sclerosis. Evidence of interferon beta-1a dose response in relapsing-remitting MS: the OWIMS Study. The Once Weekly Interferon for MS Study Group. Efficacy of intravenous pulse cyclophosphamide treatment versus combination of intravenous dexamethasone and oral cyclophosphamide treatment in steroid-resistant nephrotic syndrome. A short-term randomized MRI study of high-dose oral vs intravenous methylprednisolone in MS. The bioavailability of IV methylprednisolone and oral prednisone in multiple sclerosis. A phase I/II dose-escalation trial of vitamin D3 and calcium in multiple sclerosis. Does adjuvant nutritional support diminish steroid dependency in Crohn disease? Placebo-controlled multicentre randomised trial of interferon beta-1b in treatment of secondary progressive multiple sclerosis. European Study Group on interferon beta-1b in secondary progressive MS.
An intravenous rather than oral course of methylprednisolone is often prescribed for treating acute relapses in multiple sclerosis (MS) despite the lack of evidence to support this route of administration. Our double-blind placebo-controlled randomised trial was designed to compare the efficacy of commonly used intravenous and oral steroid regimens in promoting recovery from acute relapses in MS.
                42 patients with clinically definite relapse in MS received oral, and 38 intravenous, methylprednisolone. Clinical measurements at entry and at 1 week, 4 weeks, 12 weeks, and 24 weeks included Kurtzke's expanded disability status scale (EDSS), Hauser's Ambulatory Index, and an arm-function index. The primary outcome criterion was a difference between the two treatment groups of one or more EDSS grades at 4 weeks.
                There were no significant differences between the two groups at any stage of the study in any measurement taken: the mean difference in EDSS at 4 weeks (adjusted for baseline level) was 0.07 grades more in those taking oral steroids (95% CI -0.46 to 0.60). The most optimistic outcome for intravenous therapy is an average benefit of less than half a grade improvement on EDSS over oral treatment.
                Since our study did not show any clear advantage of the intravenous regime we conclude that it is preferable to prescribe oral rather than intravenous steroids for acute relapses in MS for reasons of patient convenience, safety, and cost. There is evidence to support both the use of intravenous methylprednisolone (IVMP) in multiple sclerosis (MS) relapse and physiotherapy in the management of MS, but no studies have investigated the combination of steroids and rehabilitation together.
                To evaluate the benefits of IVMP with planned, comprehensive multidisciplinary team (MDT) care compared to IVMP with standard care.
                In this randomised controlled trial, patients confirmed to have had a definite MS relapse severe enough to warrant IVMP (1 g daily for three days) were randomised to two groups. The control group was managed according to the standard ward routine; the treatment group received planned coordinated multidisciplinary team assessment and treatment. Baseline assessments, including demographics and Expanded Disability Status Scale (EDSS) were carried out on both groups. The primary outcome measures were Guy's Neurological Disability Scale (GNDS), and Amended Motor Club Assessment (AMCA). The secondary measures were the Barthel Index (BI), Human Activity Profile (HAP), and Short Form Item 36 Health Survey (SF-36). All measures have published data on reliability and validity. Measures were administered at one and three months.
                Forty subjects, including 27 females, completed data collection. There were no significant differences between the two groups at baseline. Results showed statistically significant differences in GNDS (p = 0.03), AMCA (p = 0.03), HAPM (p < 0.01), HAPA (p = 0.02), and BI (p = 0.02) at three months in favour of planned MDT care.
                This study indicates that combining steroids with planned MDT care is superior to administering them in a standard neurology or day ward setting. Further research is necessary in order to confirm this finding. A randomised double-blind placebo-controlled trial of intravenous methylprednisolone versus oral methylprednisolone at equivalent high dose was carried out on 35 patients with an acute relapse of multiple sclerosis (MS). After baseline evaluation each was randomly allocated to oral treatment and intravenous placebo or intravenous treatment and oral placebo, receiving 500 mg of methylprednisolone for five consecutive days and with reassessment at days five and twenty-eight. There was no significant difference in response when disability or functional scores were compared in the two groups. Adverse effects were minor and equally distributed. In this study oral treatment with methylprednisolone was as effective as intravenous treatment in acute relapse of MS. Ninety-eight patients with multiple sclerosis (MS) in the chronic progression phase entered a 3-year clinical trial to determine if azathioprine (AZ) alone or with adrenal cortical steroids stabilizes the course of MS. In group AM, the patients took AZ throughout and methylprednisolone (MP) for the first 36 weeks. Group AP received AZ and placebo instead of MP. Group PP took placebos for both drugs. We adjusted the AZ to maintain the total white blood cell count within 3,000 to 4,000/mm3; we gave the MP in a fixed dose "pulse" and alternate-day regimen. The "intent-to-treat" groups had no statistically significant differences in the rates of progression among the 3 treatments. Subgroup analysis suggests that patients in the AM group who completed treatment exactly according to protocol did statistically significantly better than the placebo recipients using the sum of Standard Neurological Examination scores, slightly better using the quantitative neuro-performance tests, but no better using Mickey's Illness Severity Scores or Kurtzke's Disability Status Scale. Also, the AZ-treated groups had half the relapse rate of the placebo-treated group. Adverse reactions to AZ accounted for most withdrawals. Hematologic and hepatic abnormalities were significantly associated with AZ, but serious non-MS abnormalities were uncommon and were equally distributed among the 3 groups. Addition of MP to the AZ slightly improved the efficacy of the treatment, but also increased the adverse effects. The benefits of AZ with or without steroids did not outweigh the risks, and therefore we do not recommend this treatment for patients with chronic progressive MS. To compare efficacy of interferon beta-1a, 22 microg or 44 microg weekly, with placebo in relapsing MS.
                Uncertainty exists concerning the optimal dose regimen for interferon beta in relapsing-remitting MS. Many patients and physicians prefer the convenience and lesser side effects of an injection given once weekly (qw) as opposed to three times weekly. Pharmacokinetic data and information on biologic markers suggest that this frequency may be suboptimal.
                Randomized, double-blind study of interferon beta-1a 22 microg, 44 microg, or placebo administered by weekly subcutaneous injection for 48 weeks. Proton density (PD)/T2-weighted and T1-weighted-gadolinium MRI scans during 24 weeks of therapy were analyzed for the number of combined unique (CU) lesions (primary outcome). Biannual PD/T2 scans were analyzed for T2 activity and burden of disease (BOD).
                CU lesions at 24 weeks had a median of 0.71/scan with placebo, 0.5/scan with 22 microg (not significant), and 0.33/scan with 44 microg (p = 0.002). T2 new lesion count/scan (mean/median) at 48 weeks was 3.2/1.5 for placebo, 2.4/1.0 for 22 microg (p = 0.03), and 1.5/1.0 for 44 microg (p = 0.0005). BOD at 48 weeks showed a median increase of 5.9% for placebo compared with a decrease of 1.4% in the 44 microg group (p = 0.0058) and 2% in the 22 microg group (p = 0.0018). No clinical variable, apart from steroid use in the 44 microg qw group (p = 0.014), showed significance.
                These data confirm an MRI benefit of interferon beta-1a at low dose in MS, but highlight the limited clinical effect. Taken together with other studies, the data demonstrate a dose-effect relationship for both clinical and MRI variables. We compared, in a randomized controlled trial, the efficacy of a regimen based on intravenous (i.v.) cyclophosphamide therapy with a combination of i.v. dexamethasone and oral cyclophosphamide therapy in inducing remission in patients with steroid-resistant nephrotic syndrome (SRNS). During April 2001 to December 2003, 52 consecutive patients with idiopathic SRNS, normal renal function and renal histology findings showing minimal change disease, focal segmental glomerulosclerosis or mesangioproliferative glomerulonephritis were enrolled into the study. Patients in group I received i.v. injection of cyclophosphamide once a month for 6 months and prednisolone on alternate days. Those in group II received i.v. treatment with dexamethasone (initially on alternate days, later fortnightly and monthly; total 14 doses), oral cyclophosphamide therapy (for 3 months) and prednisolone on alternate days. Data from 49 patients (26 in group I, 23 in group II) were analyzed; their clinical and biochemical features were similar at inclusion. Following treatment, complete remission was seen in 53.8% and 47.8% patients in groups I and II, respectively (P = 0.6). Long-term follow up showed favorable outcome in 14 (53.8%) patients in group I, and 9 (39.1%) in group II. Chief adverse effects, including cushingoid features and serious infections, were similar in both groups. Patients receiving i.v. dexamethasone therapy commonly showed hypertension and hypokalemia, while vomiting and reversible alopecia occurred in those receiving i.v. treatment with cyclophosphamide. In patients with SRNS, the efficacy of treatment intravenously with cyclophosphamide and orally with prednisolone was similar to the combination of dexamethasone intravenously, orally administered cyclophosphamide and prednisolone. To compare the efficacy, tolerability, and safety of IV methylprednisolone (IV MP) vs oral methylprednisolone (oMP) at equivalent high doses in patients with multiple sclerosis (MS) experiencing a recent relapse.
                Patients with a clinical relapse within the previous 2 weeks and at least 1 gadolinium (Gd)-enhancing lesion on a screening brain MRI scan were included. Forty patients with MS were randomized to receive either 1 g/day for 5 days of oMP (20 patients) or 1 g/day for 5 days of IV MP (20 patients). Expanded Disability Status Scale (EDSS) and brain MRI (dual-echo and postcontrast T1-weighted scans) were assessed at baseline and at weeks 1 and 4. The study primary research question (endpoint) was to compare the efficacy of the 2 treatment routes in reducing the number of Gd-enhancing lesions after 1 week from treatment initiation. Secondary outcomes were safety, tolerability, and clinical efficacy profiles of the 2 routes of administration.
                The 2 groups showed a reduction of Gd-enhancing lesions over time (p = 0.002 for oMP and p = 0.001 for IV MP) with a "non-inferiority effect" between the 2 routes of administration at week 1. Both groups showed an improvement of EDSS over time (p < 0.001) without between-group difference at week 4. Both treatments were well-tolerated and adverse events were minimal and occurred similarly in the 2 treatment arms.
                Oral methylprednisolone (oMP) is as effective as IV methylprednisolone in reducing gadolinium-enhancing lesions in patients with MS soon after an acute relapse with similar clinical, safety, and tolerability profiles. This study provides class III evidence that 1 g oMP x 5 days is not inferior to 1 g IV MP x 5 days in reducing the number of gadolinium-enhancing lesions over a period of 1 week (mean difference in lesion reduction comparing IV MP to oMP is -20%, 95% confidence interval -48% to + 5%). Oral prednisone (1)might be a convenient, inexpensive alternative to IV methylprednisolone (IVMP) if the bioequivalent dose was known. We compared the total amount of steroid absorbed after 1250 mg oral prednisone vs 1 gram IVMP in 16 patients with multiple sclerosis (MS). At 24 hours, the mean area under the concentration-time curve (AUC), the main component of bioavailability, did not differ between groups (p = 0.122). This suggests that the amount of absorbed corticosteroid is similar after either steroid at these doses. Low vitamin D status has been associated with multiple sclerosis (MS) prevalence and risk, but the therapeutic potential of vitamin D in established MS has not been explored. Our aim was to assess the tolerability of high-dose oral vitamin D and its impact on biochemical, immunologic, and clinical outcomes in patients with MS prospectively.
                An open-label randomized prospective controlled 52-week trial matched patients with MS for demographic and disease characteristics, with randomization to treatment or control groups. Treatment patients received escalating vitamin D doses up to 40,000 IU/day over 28 weeks to raise serum 25-hydroxyvitamin D [25(OH)D] rapidly and assess tolerability, followed by 10,000 IU/day (12 weeks), and further downtitrated to 0 IU/day. Calcium (1,200 mg/day) was given throughout the trial. Primary endpoints were mean change in serum calcium at each vitamin D dose and a comparison of serum calcium between groups. Secondary endpoints included 25(OH)D and other biochemical measures, immunologic biomarkers, relapse events, and Expanded Disability Status Scale (EDSS) score.
                Forty-nine patients (25 treatment, 24 control) were enrolled [mean age 40.5 years, EDSS 1.34, and 25(OH)D 78 nmol/L]. All calcium-related measures within and between groups were normal. Despite a mean peak 25(OH)D of 413 nmol/L, no significant adverse events occurred. Although there may have been confounding variables in clinical outcomes, treatment group patients appeared to have fewer relapse events and a persistent reduction in T-cell proliferation compared to controls.
                High-dose vitamin D (approximately 10,000 IU/day) in multiple sclerosis is safe, with evidence of immunomodulatory effects.
                This trial provides Class II evidence that high-dose vitamin D use for 52 weeks in patients with multiple sclerosis does not significantly increase serum calcium levels when compared to patients not on high-dose supplementation. The trial, however, lacked statistical precision and the design requirements to adequately assess changes in clinical disease measures (relapses and Expanded Disability Status Scale scores), providing only Class level IV evidence for these outcomes. Nutritional therapy plays an important role in the management of Crohn disease, particularly during the acute phase. Nutritional supplementation may also prevent relapses during the quiescent phase of Crohn disease, though this aspect has not been widely explored.
                Thirty-three patients with Crohn disease in remission were studied. All had steroid-dependent disease. Patients were randomized to receive either elemental diet (n = 19, EO28 Extra) or polymeric diet (Forticips, n = 14). The supplement was given orally in addition to normal food in an amount to provide 35%-50% of pre-trial total calorie intake. Prednisolone was withdrawn gradually. Patients were followed up for 12 months. Failure was defined as increase in CDAI by 100 points from baseline to >200, inability to withdraw chronic steroid therapy completely, need for surgery or steroid therapy.
                The nutritional supplement was successful in 14 (43%) patients who remained in remission for 12 months with complete withdrawal of steroids. The response to elemental diet (42%) was similar to that of polymeric diet (43%). Nutrition supplement failed in 13 (39%). Six (18%) patients were intolerant to enteral feeding because of smell and taste problems. Per-protocol analysis of data indicated that the success rate of nutrition supplement in steroid-dependent patients was 52% (14 out of 27 patients). No disease or patient-related factors helped predict the response to nutrition supplement.
                Nutritional supplementation with either an elemental or polymeric diet may provide a safe and effective alternative to chronic steroid therapy in patients with steroid-dependent Crohn disease. The beneficial effects of interferon beta have only been shown for patients in the relapsing-remitting phase of multiple sclerosis (MS). The role of interferon beta in the treatment of patients who are in the secondary progressive phase of the disease (SP-MS), and for whom no effective drug treatment is available, has not been assessed.
                In this multicentre, double-masked, randomised, placebo-controlled trial, outpatients with SP-MS having scores of 3.0-6.5 on the Expanded Disability Status Scale (EDSS) received either 8 million IU interferon beta-1b every other day subcutaneously, or placebo, for up to 3 years. The primary outcome was the time to confirmed progression in disability as measured by a 1.0 point increase on the EDSS, sustained for at least 3 months, or a 0.5 point increase if the baseline EDSS was 6.0 or 6.5. A prospectively planned interim analysis of safety and efficacy of the intention-to-treat population was done after all patients had been in the study for at least 2 years.
                358 patients with SP-MS were allocated placebo and 360 were allocated interferon beta-1b; 57 patients (31 placebo, 26 interferon beta-1b) were lost to follow-up. There was a highly significant difference in time to confirmed progression of disability in favour of interferon beta-1b (p=0.0008). Interferon beta-1b delayed progression for 9-12 months in a study period of 2-3 years. The odds ratio for confirmed progression was 0.65 (95% CI 0.52-0.83). This beneficial effect was seen in patients with superimposed relapses and in patients who had only progressive deterioration without relapses. Positive results were also obtained regarding time to becoming wheelchair-bound, relapse rate and severity, number of steroid treatments and hospital admissions, as well as on magnetic resonance imaging variables. The drug was safe and side effects were in line with previous experience with interferon beta-1b. The study was stopped after the interim results gave clear evidence of efficacy.
                Treatment with interferon beta-1b delays sustained neurological deterioration in patients with SP-MS. Interferon beta-1b is the first treatment to show a therapeutic effect in patients with SP-MS.
The analysis of the five included trials comparing intravenous versus oral steroid therapy for MS relapses do not demonstrate any significant differences in clinical (benefits and adverse events), radiological or pharmacological outcomes. Based on the evidence, oral steroid therapy may be a practical and effective alternative to intravenous steroid therapy in the treatment of MS relapses.