Periarticular Bone Loss Inhibition Linked to Clinical Remission in RA

hand RA xray
hand RA xray
Investigators examined the relationship between metacarpal bone mineral density, as assessed by digital x-ray radiogrammetry, and clinical remission and ACR70 response in patients with rheumatoid arthritis treated with certolizumab pegol.

After 1 year, patients with rheumatoid arthritis (RA) who take certolizumab pegol (CZP) demonstrated reduced periarticular bone loss compared with patients who take a placebo, as measured by digital x-ray radiogrammetry (DXR). Clinical remission and 70% improvement according to American College of Rheumatology criteria (ACR70 response) were also associated with lower rates of demineralization compared with rates in nonresponders and patients not in remission, according to findings published in Rheumatology International.

Metacarpal demineralization is an early hallmark of RA that is well suited for detection by automated DXR, which offers excellent sensitivity and specificity. However, only a few trials have examined the effect of anti-inflammatory therapies on the loss of hand bone mineral density (BMD) and little data exist on this effect in the RA population. In addition, CZP has never been explored in this context.

A retrospective post hoc secondary analysis of data from the RA Prevention of Structural Damage 1 trial — a phase 3, 52-week, randomized, multicenter, parallel-group, double-blind, placebo-controlled study — enrolled a total of 345 patients. All participants were treated with methotrexate (MTX) plus either placebo (n=34; mean age, 50.6 years; 85.3% women; mean disease duration, 6.6 years), CZP 200 mg (n=155; mean age, 50.5 years; 77.4% women; mean duration, 6.4 years) or CZP 400 mg (n=156; mean age, 51.6 years; 83.3% women; mean duration, 5.8 years).

At 52 weeks, DXR was used to assess BMD loss as g/cm2 change from baseline. A modified total Sharp Score estimated radiographic disease progression. Clinical remission was defined as a 28-joint Disease Activity Score (DAS28) <2.6 and was used along with ACR70 achievement as variables potentially associated with less demineralization. The primary outcome was BMD change over 1 year whereas the secondary outcomes were the strength of associations between BMD change and remission or ACR70 response. In addition to separation according to treatment, the cohort was also divided into patients with DAS28 ≤2.6 and DAS28 >2.6 and into ACR70 responders and nonresponders.

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Over the study course, substantially larger changes were determined in DAS28 for patients who received MTX plus CZP 400 mg (median, −3.53 g/cm2; range, −6.77 to 0.48 g/cm2) and MTX plus CZP 200 mg (median, −3.13 g/cm2; range, −6.37 to −0.52 g/cm2) compared with patients taking MTX plus placebo (median, −2.41 g/cm2; range, −4.76 to 0.31 g/cm2). Regarding BMD, DXR revealed minimal loss in the CZP 200 mg (median, −0.009 g/cm2; range, −0.059 to 0.095 g/cm2) and CZP 400 mg (median, −0.008 g/cm2; range, −0.064 to .08 g/cm2 ) groups compared with the placebo group (median, −0.024 g/cm2; range, −0.102 to 0.057 g/cm2), which saw advanced metacarpal periarticular loss. In both CZP groups, patients who had achieved remission and ACR70 response had nonsignificant bone loss whereas patients who did not achieve 1 or both of these benchmarks had significant decreases in BMD (P <.01).

Study limitations included the small sample size of the placebo group.

“DXR should now be considered as a tool, sensitive enough to assess minor differences archiving in therapies for patients with RA and also allowing a more optimal individualized treatment,” the authors noted.

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Pfeil A, Nussbaum A, Renz DM, et al. Inhibition of periarticular bone loss is associated with clinical remission and ACR70-Response in rheumatoid arthritis [published online December 19, 2018]. Rheumatol Int. doi:10.1007/s00296-018-4226-7