Comparison of the effects of tocilizumab monotherapy and adalimumab in combination with methotrexate on bone erosion repair in rheumatoid arthritis

Abstract

ObjectiveTo compare the effects of interleukin-6 (IL-6) receptor and tumour necrosis factor inhibition on inducing repair of existing bone erosions in patients with very early rheumatoid arthritis (RA).MethodsProspective non-randomised observational study in patients with active erosive RA with inadequate response to methotrexate (MTX) receiving either tocilizumab (TOC) monotherapy or adalimumab (ADA) with MTX for 52 weeks. Erosion volumes were assessed in metacarpal heads (MCH) and the radius by high-resolution peripheral quantitative CT at baseline and after 52 weeks. Clinical response was monitored using Clinical Disease Activity Index, Simple Disease Activity Index and Disease Activity Score 28-erythrocyte sedimentation rate (DAS28-ESR) scores every 12 weeks.ResultsTOC (N=33) and ADA/MTX (N=33) treatment groups were balanced for age, sex, body mass index, comorbidities, disease and activity, functional state, autoantibody status, baseline bone damage and baseline bone biomarkers. Both TOC (DAS28-ESR: baseline: 6.2±0.5; 52 weeks: 2.3±1.0) and ADA/MTX (6.3±0.6; 2.8±1.2) significantly reduced disease activity. Erosion volumes significantly decreased in the MCH and radius of patients with RA treated with TOC (p<0.001) but not in patients treated with ADA/MTX (p=0.77), where they remained stable in size. Mean decrease in erosion volume in TOC-treated patients was −1.0±1.1 mm3 and −3.3±5.9 mm3 in the MCH and radius of TOC-treated patients, respectively, and −0.05±0.9 mm3 and −0.08±4.1 mm3 in patients treated with ADA/MTX.ConclusionsThe REBONE study shows that TOC monotherapy achieves more pronounced repair of existing bone erosions than ADA/MTX. Hence, IL-6 is a central factor for the disturbed bone homeostasis in the joints of patients with RA.

Translating IL-6 biology into effective treatments

“…On the basis of these results, EULAR recommendations for the management of RA named IL-6 pathway inhibitors as one of the preferred treatment options for patients for whom methotrexate is inappropriate 60 . Interestingly, the clinical benefits of IL-6 inhibition might be attributable, in part, to the beneficial effects of IL-6 inhibition on bone and cartilage turnover, which are supported by data from prospective cohort studies showing that tocilizumab monotherapy achieves better repair of focal bone erosions than TNF inhibition in patients with RA [60][61][62][63][64][65][66][67][68][69][70] . Besides promoting joint inflammation and damage through effects on chondrocytes, osteoclasts, macrophages and fibroblasts, IL-6 mediates systemic inflammation in RA.…”

High-Resolution Peripheral Quantitative Computed Tomography for Bone Evaluation in Inflammatory Rheumatic Disease

“…Conversely, erosion volume increased significantly in patients receiving alendronate, while decreasing significantly in patients receiving denosumab after 6 months. While these represent the shortest time interval over which changes in erosion volume and JSW have been observed, two studies have shown decreases in erosion volume in response to tocilizumab in combination with methotrexate for both patients with newly diagnosed RA (59) and established RA (15); this has also been observed for patients with established RA treated with TNFi in combination with methotrexate (6) over a 1-year follow-up. Stabilization in erosion size with therapy has also been demonstrated, in newly diagnosed patients with RA on treatment with a TNFi in combination with methotrexate (59).…”

“…Fifteen studies have reported longitudinal changes in the number and/or size of erosions. Of these, three investigated PsA (14,49,66), 10 investigated patients with RA (6,10,15,29,42,46,58,59,64,65), and one study examined ACPA+ individuals without arthritis (62). Seven studies investigated intervention with different therapies either as an open-label study or secondary analysis in a randomized controlled trial.…”

Connective tissue remodelling is differently modulated by Tocilizumab versus Methotrexate monotherapy in patients with early Rheumatoid Arthritis: the AMBITION study

“…However, therapies involving MTX often have inadequate response or intolerance, which calls for alternative treatments such as biological agents [6]. One of them is Tocilizumab (TCZ), a humanized anti-IL-6 receptor monoclonal antibody, which acts by blocking IL-6 signaling [7][8][9]. Elevated levels of IL-6 in synovial uid and serum correlate with disease activity in patients with RA [10][11].…”

“…Elevated levels of IL-6 in synovial uid and serum correlate with disease activity in patients with RA [10][11]. Inhibition of the IL-6 signaling by TCZ showed a protective effect on bone erosions by decreasing their volume in RA patients and signi cant reduction of swollen and tender joint counts with concurrent improvement in radiographic progression [12] [9].…”