Trial of Ibudilast in progressive multiple sclerosis

There are limited treatments for progressive multiple sclerosis. Ibudilast inhibits several cyclic nucleotide phosphodiesterases, macrophage migration inhibitory factor, and toll-like receptor 4 and can cross the blood-brain barrier, with potential salutary effects in progressive multiple sclerosis.

Two hundred and fifty-five appropriate patients were randomised to either oral ibudilast or placebo for 96 weeks. The primary endpoint was the rate of brain atrophy.

Ibudilast was associated with slower progression of brain atrophy than placebo but was associated with higher rates of gastrointestinal side effects, headache and depression. Further trials are needed to identify whether the effects on brain atrophy is reproducible and is associated with slowed progression of neurologic disability.

N Engl J Med 2018; 379:846–55

Sulfonylureas as second-line drugs in type 2 diabetes and the risk of cardiovascular and hypoglycaemic events

Metformin is the drug of choice in the management of type 2 diabetes. If this treatment fails, the patient is often switched to treatment with a sulfonylurea. This cohort study evaluates the safety of this change of treatment.

Among 77,138 metformin initiators, 25,699 added or switched to sulfonylureas during the study period. During a mean follow-up period of 1.1 years, sulfonylureas were associated with an increased risk of myocardial infarction, HR (hazard ratio) of 1.26 and an increased risk of all-cause mortality, HR 1.28 and an increased risk of severe hypoglycaemia, HR 7.6.

It was concluded that sulfonylureas as second-line drugs are associated with an increased risk of myocardial infarction, all-cause mortality and severe hypoglycaemia, compared with remaining on metformin monotherapy. Continuation of metformin when introducing sulfonylureas is safer than switching.

BMJ 2018; 362:k2693

Hospitalisation and morbidity due to adverse drug reactions in elderly patients

Adverse drug reaction (ADR) is a leading but under-recognised cause of illness, particularly in frail subjects with multiple comorbidities. In this report from Italy the researchers investigate the frequency, patterns and outcomes of ADR as a cause of hospitalisation in elderly patients admitted to an internal medicine ward.

Their retrospective observational study included every patient aged 65 years or over who was admitted to their department over one year. ADR accounted for 6.1% of the 1,750 admissions. The median age of the patients was 83.5 years and 56.6% were on polypharmacy. Diuretics were the most commonly imputed drugs followed by antithrombotics and central nervous system-active drugs.

The researchers observed that ADR are a common cause of hospital admission in elderly patients and are often associated with adverse outcomes. Their data underline the need of appropriate strategies aimed at identifying high-risk patients and avoiding potentially preventable drug toxicities.

Internal Medicine Journal 2018; 48:1192–1197

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