From the Journals

Glucocorticoid use linked to mortality in RA with diabetes



Glucocorticoid use is associated with greater mortality and cardiovascular risk in RA patients, and the associated risk is greater still in patients with RA and comorbid diabetes. The findings come from a new retrospective analysis derived from U.K. primary care records.

Although patients with diabetes actually had a lower relative risk for mortality than the nondiabetes cohort, they had a greater mortality difference because of a greater baseline risk. Ultimately, glucocorticoid (GC) use was associated with an additional 44.9 deaths per 1,000 person-years in the diabetes group, compared with 34.4 per 1,000 person-years in the RA-only group.

The study, led by Ruth Costello and William Dixon, MBBS, PhD of the University of Manchester (England), was published in BMC Rheumatology.

The findings aren’t particularly surprising, given that steroid use and diabetes have associated cardiovascular risks, and physicians generally try to reduce or eliminate their use. “There’s a group [of physicians] saying that we don’t need to use steroids at all in rheumatoid arthritis, except maybe for [a] short time at diagnosis to bridge to other therapies, or during flares,” Gordon Starkebaum, MD, professor emeritus of rheumatology at the University of Washington, Seattle, said in an interview. He recounted a session at last year’s annual meeting of the American College of Rheumatology that advocated for only injectable steroid use during flare-ups. “That was provocative,” Dr. Starkebaum said.

“It’s a retrospective study, so it has some limitations, but it provides good insight, and some substantiation to what we already think,” added Brett Smith, DO, a rheumatologist practicing in Knoxville, Tenn.

Dr. Smith suggested that the study further underscores the need to follow treat-to-target protocols in RA. He emphasized that lifetime exposure to steroids is likely the greatest concern, and that steady accumulating doses are a sign of trouble. “If you need that much steroids, you need to go up on your medication – your methotrexate, or sulfasalazine, or your biologic,” said Dr. Smith. “At least 50% of people will need a biologic to [achieve] disease control, and if you get them on it, they’re going to have better disease control, compliance is typically better, and they’re going to have less steroid exposure.”

Dr. Smith also noted that comorbid diabetes shouldn’t affect treat-to-target strategies. In fact, in such patients “you should probably be following it more tightly to reduce the cardiovascular outcomes,” he said.

The retrospective analysis included 9,085 patients with RA and with or without type 2 diabetes, with a mean follow-up of 5.2 years. They were recruited to the study between 1998 and 2011. Among patients with comorbid diabetes, those exposed to GC had a mortality of 67.4 per 1,000 person-years, compared with 22.5 among those not exposed to GC. Among those with RA alone, mortality was 44.6 versus 10.2 with and without GC exposure, respectively. Those with diabetes had a lower risk ratio for mortality (2.99 vs. 4.37), but a higher mortality difference (44.9 vs. 34.4 per 1,000 person-years).

“The increased absolute hazard for all-cause mortality indicates the greater public health impact of people with RA using GCs if they have [diabetes],” the researchers wrote. “Rheumatologists should consider [diabetes] status when prescribing GCs to patients with RA given this potential impact of GC therapy on glucose control and mortality.”

The study was limited by a lack of information on GC dose and cumulative exposure. Given its retrospective nature, the study could have been affected by confounding by indication, as well as unknown confounders.

The study was funded by the Centre for Epidemiology Versus Arthritis and the National Institute for Health Research Biomedical Research Centre. Dr. Starkebaum has no relevant financial disclosures. Dr. Smith is on the speaker’s bureau for AbbVie and serves on the company’s advisory board. He is also on the advisory boards of Regeneron and Sanofi Genzyme.

SOURCE: Costello R et al. BMC Rheumatol. 2020 Feb 19. doi: 10.1186/s41927-019-0105-4.

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