IL-6 receptor inhibition may induce bone erosion repair in RA
medwireNews: Patients with early rheumatoid arthritis (RA) who are treated with the interleukin (IL)-6 receptor inhibitor tocilizumab experience more pronounced repair of bone erosions than those given adalimumab plus methotrexate, indicate findings from the REBONE study.
The prospective observational study included 66 patients with active RA and existing bone lesions despite at least 3 months of methotrexate treatment who opted to either switch to tocilizumab monotherapy or receive the tumor necrosis factor (TNF)α inhibitor adalimumab in combination with methotrexate.
Georg Schett (Universitӓtsklinikum Erlangen, Germany) and co-investigators found that bone erosion volume at the metacarpal head decreased significantly from an average of 1.87 mm3 at baseline to 0.84 mm3 at the 1-year follow among the 33 participants receiving tocilizumab.
Conversely, their 33 counterparts balanced for age, sex, and BMI who were given adalimumab plus methotrexate did not experience a significant reduction in bone erosion volume, with average measures of 1.89 mm3 at baseline and 1.83 mm3 at 1 year.
At the individual participant level, the researchers say that erosion volumes in both the metacarpal head and the radius significantly decreased “in the vast majority of patients” treated with tocilizumab, but “no significant regression of erosions” occurred among patients given adalimumab plus methotrexate.
The team also analyzed markers of bone metabolism, finding that levels of osteocalcin – a standard marker of bone formation – increased significantly in patients treated with tocilizumab but not in those given adalimumab plus methotrexate. However, no significant effect of either treatment on CTXI, a marker of bone resorption, was observed.
These data indicate that “IL-6 is a central factor for the disturbed bone homeostasis in the joints of patients with RA,” and “that IL-6 exerts a more fundamental effect on the generation of bone erosions than TNFα,” write Schett and colleagues in the Annals of the Rheumatic Diseases.
They report that the bone erosion benefits observed with tocilizumab occurred despite people in both groups experiencing “virtually identical” improvements in disease control.
For example, average DAS28-ESR score improved by 3.2 points from baseline to month 3 in the tocilizumab group and by 3.0 points in the combination group, and improvements were maintained until the 1-year follow-up. The researchers add that tender and swollen joint counts “decreased rapidly” in both treatment groups.
The researchers caution that their study had a number of limitations, including small participant numbers and a nonrandomized design. They point out that “co-treatment with [methotrexate] may have blunted osteoblast responses in the [adalimumab] treatment arm,” but note that “positive effects on osteoblasts have previously been observed also in patients receiving [tocilizumab plus methotrexate] combination treatment.”
And they conclude: “It remains to be determined whether erosion repair turns into better functional outcomes.”
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