Late-onset axial spondyloarthritis: about 13% of cases, with less HLA-B27 positivity

Design

Systematic review and meta-analysis with logistic-normal and random-effects pooling

Population

54 reports (42 independent studies); 745 late-onset cases among 6,631 patients in the primary set

Primary outcome

Proportion of late-onset cases and comparison of later- versus earlier-onset phenotypes

Effect

Late-onset proportion 13.43% (95% CI 9.23% to 19.14%); HLA-B27 OR 0.47 (0.34 to 0.67)

A systematic review of 54 reports (42 independent studies) estimated the proportion of axial spondyloarthritis cases with onset after age 45. In six study families, 745 late-onset cases arose among 6,631 patients with assessable onset age, giving a pooled proportion of 13.43% (95% CI 9.23% to 19.14%; prediction interval 3.63% to 39.02%; I-squared 93.3%; very low certainty).

HLA-B27 positivity was lower in later-onset disease (four studies, 2,593 patients; odds ratio 0.47, 95% CI 0.34 to 0.67; moderate certainty). Male sex, radiographic sacroiliitis and BASDAI differences were inconclusive.

The authors stress that the HLA-B27 association rests on four unadjusted comparisons and cannot be interpreted causally or diagnostically. A negative HLA-B27 test in an older patient with inflammatory back pain does not rule out axial spondyloarthritis. The proportion of late-onset cases varies so widely between cohorts that 13% is a rough guide only.

• About 13.4% of cases began after age 45, with very low certainty and wide variation.
• HLA-B27 positivity was lower with later onset (OR 0.47).
• Male sex and radiographic sacroiliitis comparisons were inconclusive.
• The HLA-B27 finding rests on four unadjusted comparisons.
• Do not exclude axial spondyloarthritis in an older patient because HLA-B27 is negative.

Why it matters

Classification and referral pathways are built on young-onset disease, so older patients are likely to be diagnosed late.

Don't overread it

The prevalence estimate is very low certainty and the HLA-B27 association is not a diagnostic rule.

The statistics, in plain English

An I-squared of 93% means almost all the variation between studies is real rather than chance, so the pooled proportion hides a very wide range (3.6% to 39.0% in the prediction interval). An odds ratio of 0.47 means about half the odds of being HLA-B27 positive.

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