A randomised controlled trial of intravenous immunoglobulin in IgM paraprotein associated demyelinating neuropathy. Intravenous immunoglobulin treatment in patients with motor neuron syndromes associated with anti-GM1 antibodies: a double-blind, placebo-controlled study. A controlled trial of high-dose intravenous immune globulin infusions as treatment for dermatomyositis. Randomized controlled trial of intravenous immunoglobulin versus oral prednisolone in chronic inflammatory demyelinating polyradiculoneuropathy.
This multicentre randomised double blind crossover trial tested the short term efficacy of intravenous immunoglobulin (IVIg) 2.0 g/kg given over 24 or 48 hours in patients with paraproteinaemic demyelinating neuropathy (PDN). Twenty-two patients were randomised and completed the trial. After 2 weeks, the overall disability grade decreased during both IVIg treatment and placebo but neither change was significant nor was the mean difference between the treatment effects. After 4 weeks the overall disability decreased by a mean of 0.55 [0.67] grades during the IVIg period (p = 0.001) while it was substantially unmodified during the placebo period. The mean difference between the treatment effects was significant (p = 0.05). Overall during the IVIg period 10 patients improved and 11 were stable and one got worse. During the placebo period 4 patients improved, 4 deteriorated and 14 were stable. Many secondary outcome measures, including Rankin scale, time to walk 10 metres, grip strength, sensory symptoms score were significantly better during IVIg treatment. Two serious adverse events occurred during the trial, both during placebo treatment. In conclusion the trial showed some short-term benefit of IVIg in about half of the patients confirming previous observation. We studied the effects of intravenous immunoglobulin (IVIg) in 12 patients with motor neuron syndromes associated with high titers of anti-GM1 antibodies. Five of the patients had conduction blocks. The study design was a double-blind, placebo-controlled, crossover trial with IVIg (0.4 g/kg body weight per day injected for 5 consecutive days). We evaluated the patients before and 5, 28, and 56 days after drug administration using a computerized analyzer for muscle strength, the Norris scale for disability, motor nerve conduction velocities for patients with conduction blocks, and measurements of immunologic markers. Compared with placebo, IVIg induced a significant increase in muscle strength only in the patients with conduction blocks. Dermatomyositis is a clinically distinct myopathy characterized by rash and a complement-mediated microangiopathy that results in the destruction of muscle fibers. In some patients the condition becomes resistant to therapy and causes severe physical disabilities.
                We conducted a double-blind, placebo-controlled study of 15 patients (age, 18 to 55 years) with biopsy-proved, treatment-resistant dermatomyositis. The patients continued to receive prednisone (mean daily dose, 25 mg) and were randomly assigned to receive one infusion of immune globulin (2 g per kilogram of body weight) or placebo per month for three months, with the option of crossing over to the alternative therapy for three more months. Clinical response was gauged by assessing muscle strength, neuromuscular symptoms, and changes in the rash. Changes in immune-mediated muscle abnormalities were determined by repeated muscle biopsies.
                The eight patients assigned to immune globulin had a significant improvement in sores of muscle strength (P < 0.018) and neuromuscular symptoms (P < 0.035), whereas the seven patients assigned to placebo did not. With crossovers a total of 12 patients received immune globulin. Of these, nine with severe disabilities had a major improvement to nearly normal function. Their mean muscle-strength scores increased from 74.5 to 84.7, and their neuromuscular symptoms improved. Two of the other three patients had mild improvement, and one had no change in his condition. Of 11 placebo-treated patients, none had a major improvement, 3 had mild improvement, 3 had no change in their condition, and 5 had worsening of their condition. Repeated biopsies in five patients of muscles whose strength improved to almost normal showed an increase in muscle-fiber diameter (P < 0.04), an increase in the number and a decrease in the diameter of capillaries (P < 0.01), resolution of complement deposits on capillaries, and a reduction in the expression of intercellular adhesion molecule 1 and major-histocompatibility-complex class I antigens.
                High-dose intravenous immune globulin is a safe and effective treatment for refractory dermatomyositis. This multicenter, randomized, double-blind, crossover trial compared a six week course of oral prednisolone tapering from 60 mg to 10 mg daily with intravenous immunoglobulin (IVIg) 2.0 g/kg given over one to two days for treating chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Twenty-four of the thirty-two randomized patients completed both treatment periods. Both treatments produced significant improvements in the primary outcome measure, change in an 11-point disability scale two weeks after randomization. There was slightly, but not significantly, more improvement after IVIg than with prednisolone, the mean difference between the groups in change in disability grade being 0.16 (95% CI = -0.35 to 0.66). There were also slightly, but not significantly, greater improvements favoring IVIg in the secondary outcome measures: time to walk 10 meters after two weeks and improvement in disability grade after six weeks. Results may have been biased against IVIg by the eight patients who did not complete the second arm of the trial. A serious adverse event (psychosis) attributable to treatment occurred in one patient while on prednisolone and in none with IVIg.
Limited evidence from randomised controlled trials shows that intravenous immunoglobulin has a beneficial effect on strength. There was a non-significant trend towards improvement in disability. More research is needed to discover whether intravenous immunoglobulin improves disability and is cost-effective.