Recombinant human insulin-like growth factor I (rhIGF-I) for amyotrophic lateral sclerosis/motor neuron disease

Background Trophic factors, including recombinant human insulin-like growth factor I ( rhIGF-I) are possible disease modifying therapies for amyotrophic lateral sclerosis. Objectives To examine the efficacy of recombinant human insulin-like growth factor I in amyotrophic lateral sclerosis. Search strategy We searched the Cochrane Neuromuscular Disease Group Trials Register ( March 2006), MEDLINE ( January 1966 to March 2006) and EMBASE ( January 1980 to March 2006) and asked the authors of randomised clinical trials and manufacturers of recombinant human insulin-like growth factor I. Selection criteria We considered all randomised controlled clinical trials involving rhIGF-I treatment of amyotrophic lateral sclerosis in adults with a clinical diagnosis of definite or probable amyotrophic lateral sclerosis according to the El Escorial Criteria. The primary outcome measure was change in Appel Amyotrophic Lateral Sclerosis Rating Scale (AALSRS) total score after nine months treatment and secondary outcome measures were change in AALSRS at 1, 2, 3, 4, 5, 6, 7, 8, 9 months, change in quality of life ( Sickness Impact Profile scale), survival and adverse events. Data collection and analysis We identified three randomised clinical trials. Only two were included in the analysis. Each author graded the studies for methodological quality. Data were extracted and entered by the lead author and checked by the other two. Some missing data had to be regenerated by calculations based on ruler measurements of data presented in published graphs. Main results In a European trial with 59 participants on placebo and 124 on rhIGF-I, 0.1 mg/kg/day the mean difference ( MD) in change in AALSRS total score after nine months was -3.30 (95% confidence interval (CI) -8.68 to 2.08), non-significantly less in the treated than the placebo group. In a North American trial, in which 90 participants on placebo were compared with 89 on recombinant human insulin-like growth factor I 0.05 mg/kg/day, and 87 participants on 0.1 mg/kg/day, the MD after nine months was -6.00 ( 95% CI -10.99 to -1.01), significantly less on treatment. The combined analysis from both randomised clinical trials showed a weighted mean difference after nine months of -4.75 ( 95% CI -8.41 to -1.09), a significant difference in favour of the treated group. The secondary outcome measures showed non-significant trends favouring rhIGF-I. Similarly the data with the 0.05 mg/kg/day dose showed trends favouring rhIGF- I at all time points but did not reach significance at the five per cent level at any point. There was an increased risk of injection site reactions with rhIGF- I ( relative risk 2.53, 95% CI 1.40 to 4.59). Authors' conclusions The available randomised placebo controlled trials do not permit a definitive assessment of the clinical efficacy of rhIGF-I on ALS. More research is needed and one trial is in progress. Future trials should include survival as an outcome measure.