Infection hospitalisation differences between lupus immunosuppressants faded once glucocorticoid dose was counted

Design

Target trial emulation using claims data, inverse probability weighting, marginal structural Cox models

Population

6,168 patients with non-renal SLE starting azathioprine, belimumab, methotrexate or mycophenolic acid analogues

Primary outcome

Time to first infection-related hospitalisation

Effect

24-month incidence 8% to 13%; MPAA vs belimumab HR 1.55 (95% CI 1.07 to 2.25), not significant after steroid adjustment

This target trial emulation used US claims data for 6,168 people with non-renal lupus starting azathioprine, belimumab, methotrexate or mycophenolic acid analogues between 2011 and 2023. People with lupus nephritis or prior rituximab or cyclophosphamide were excluded.

Twenty-four-month cumulative incidence of infection-related hospitalisation was 10% with azathioprine, 8% with belimumab, 10% with methotrexate and 13% with mycophenolic acid analogues. In intention-to-treat analyses, mycophenolic acid analogues carried higher risk than belimumab (HR 1.55, 95% CI 1.07 to 2.25) and methotrexate (HR 1.32, 95% CI 1.04 to 1.68). After accounting for time-varying monthly glucocorticoid dose, the differences between drugs were no longer significant.

The authors highlight glucocorticoids as an important factor. They also point out that steroid dose may reflect disease activity and may itself be a route through which a drug affects infection, so adjusting for it is not clean.

• Review glucocorticoid dose at every visit; it was linked to serious infection risk.
• Aim to taper steroids using a steroid-sparing agent, per local guidance.
• Do not choose among these immunosuppressants on infection risk alone from this analysis.
• Ask about infections and vaccination status in every lupus review.
• Treat the apparent advantage of belimumab as unproven after adjustment.

Why it matters

Serious infection is a leading cause of hospital admission in lupus, and steroid exposure is under the clinician's control.

Don't overread it

A claims-based emulation without randomisation; unmeasured disease activity and severity could affect every comparison.

The statistics, in plain English

When a difference disappears after adjustment for steroid dose, it may be because steroids explain it, or because dose follows disease activity that also affects infection. Both are plausible, and claims data cannot separate them.

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