Bone Erosion Repair Stimulated Through Tocilizumab Therapy in RA

Compared with adalimumab plus methotrexate combination therapy, tocilizumab monotherapy results in a more pronounced repair of existing bone erosions in patients with early rheumatoid arthritis (RA), according to research published in Annals of the Rheumatic Diseases.

Researchers conducted a prospective, nonrandomized, observational study (NCT02778789) to compare the effects of interleukin (IL)-6 receptor and tumor necrosis factor inhibition on bone erosion repair in patients with very early RA. Patients included in the study had an inadequate response to methotrexate and were receiving either tocilizumab monotherapy or adalimumab plus methotrexate combination therapy for 52 weeks.

In total, 66 patients participated in the study — 33 in the tocilizumab monotherapy group and 33 in the adalimumab/methotrexate combination therapy group. Patients were balanced for age, sex, and body mass index; disease duration and activity were “virtually identical.”

Investigators assessed the clinical efficacy of each treatment every 3 months. Both treatment groups experienced a rapid decrease in tender and swollen joint counts; in general, most responses occurred within the first 3 months of treatment (Disease Activity Score in 28 joints [DAS28]: tocilizumab -3.2±1.2; adalimumab/methotrexate -3.0±0.8).

Overall, global disease activity, erythrocyte sedimentation rate DAS28, and the Clinical and Simple Disease Activity Indices responses were similar in both groups. In the tocilizumab group, 22 patients reached DAS28-erythrocyte sedimentation rate remission; 19 patients in the adalimumab/methotrexate group also achieved this remission. Twenty-one and 19 patients in each group, respectively, reached Clinical Disease Activity Index and Simple Disease Activity Index remission as well.

Sequential volume measurement of the largest erosion at the metacarpal head 2 and radius was used to assess erosion repair, with measurements performed at baseline and 1 year. In the tocilizumab group, bone erosion volumes “significantly decreased” (P <.0001 for both sites); no significant erosion regression was noted in the adalimumab/methotrexate combination therapy group. However, the adalimumab/methotrexate group did demonstrate an arrest of erosion size.

In terms of the total group, absolute erosion volume decreased in the tocilizumab group (baseline 1.87±1.69 mm³; follow up 0.84±0.91 mm³; P =.0006). Similar results were noted at the radius in the tocilizumab group (baseline 7.0±12.2 mm³; follow up 3.8±6.9 mm³; P =.103). An assessment of relative changes in erosion volumes showed a significant decline in the tocilizumab, but not the adalimumab/methotrexate group in the metacarpal head 2 and the radius (P <.0001 and P =.0015).

A limitation of the study is the small sample size; another is the lack of randomization in the REBONE study, so that channeling bias cannot be ruled out.

“These data provide first evidence for a pathway-specific induction of erosion repair in patients with RA,” the researchers of the study concluded. “Inhibition of IL-6R appears to be an effective strategy to induce damage repair in RA.”

Reference

Finzel S, Kraus S, Figueiredo CP, et al. Comparison of the effects of tocilizumab monotherapy and adalimumab in combination with methotrexate on bone erosion repair in rheumatoid arthritis [published online May 29, 2019]. Ann Rheum Dis. doi: 10.1136/annrheumdis-2018-214894