Adalimumab therapy reduces hand bone loss in early rheumatoid arthritis: explorative analyses from the PREMIER study

Objective. To investigate the relationship between synovial vascularity and progression of structural bone damage in each finger joint in patients with rheumatoid arthritis (RA) and to demonstrate synovial vascularity as a potential therapeutic marker. Methods. We studied 250 metacarpophalangeal (MCP) and 250 proximal interphalangeal (PIP) joints of 25 patients with active RA who were administered adalimumab or tocilizumab. Patients were examined with clinical and laboratory assessments. Power Doppler sonography was performed at baseline and at the fourth and eighth weeks. Synovial vascularity was evaluated according to quantitative measurement. Hand and foot radiography was performed at baseline and the twentieth week. Results. Clinical indices such as the 28-joint Disease Activity Score, the Clinical Disease Activity Index, and the Simplified Disease Activity Index were significantly decreased by biologic agents. The MCP and PIP joints with no response in synovial vascularity between baseline and the eighth week (vascularity improvement of <70% at the eighth week) showed a higher risk of radiographic progression compared with responsive joints (vascularity improvement of >70% at the eighth week; relative risk 2.33-9). Radiographic progression at the twentieth week was significantly lower in responsive joints than in nonresponsive joints. Conclusion. The improvement of synovial vascularity following treatment with biologic agents led to suppression of radiographic progression of RA in each finger joint. The alteration in synovial vascularity numerically reflected therapeutic efficacy. Using vascularity as a marker to determine the most suitable therapeutic approach would be beneficial for patients with active RA.

Section: Discussionmentioning

confidence: 83%

Radiographic prognosis of finger joint damage predicted by early alteration in synovial vascularity in patients with rheumatoid arthritis: Potential utility of power doppler sonography in clinical practice

Fukae¹,

Isobe²,

Kitano³

et al. 2011

“…We identified 11 eligible studies in patients with RA: 5 studies involved use of TNFi (total of 345 patients exposed to TNFi and 302 controls) (4,(12)(13)(14)(15) (Table 1) and 7 studies involved use of glucocorticoids (total of 445 patients exposed to glucocorticoids and 347 controls) (12,(16)(17)(18)(19)(20)(21) (Table 2). One study investigated the use of both TNFi and glucocorticoids (12) and was therefore included in both meta-analyses.…”

Section: Resultsmentioning

confidence: 99%

“…The majority of included trials had low risk of bias. A few trials had high risk of incomplete outcome data reporting, all of which were related to a disproportionately higher percentage of participants from the control group dropping out of the study (4,17,22). More than half of those who dropped out of the control group in each of these studies did so because of lack of treatment efficacy or death.…”

Section: Effect Of Steroids and Tnf Inhibitors On Bmdmentioning

confidence: 99%

Meta‐Analysis of Tumor Necrosis Factor Inhibitors and Glucocorticoids on Bone Density in Rheumatoid Arthritis and Ankylosing Spondylitis Trials

Siu

Haraoui

Bissonnette

et al. 2015

Objective. To examine the impact of antirheumatic drugs on bone mineral density (BMD) in rheumatoid arthritis (RA), ankylosing spondylitis (AS), psoriatic arthritis (PsA), and psoriasis using a systematic review. Methods. Electronic databases were systematically searched for randomized controlled trials. Studies were grouped based on disease, treatment, and site of BMD measurement. Change in BMD (DBMD) from baseline to end of study was recorded. Standardized mean difference (SMD) of DBMD between treatment and controls was standardized for meta-analyses and 95% confidence intervals (95% CIs) were calculated. Results. Treatment effects on BMD were not the primary outcomes of the trials. Thirteen studies were eligible (11 RA, 2 AS, 0 PsA, and 0 psoriasis). For RA, significantly less hand bone loss was seen with tumor necrosis factor inhibitors (TNFi; SMD DBMD 0.33 [95% CI 0.13, 0.53], P 5 0.001, I 2 5 0%) and glucocorticoids (SMD DBMD 0.51 [95% CI 0.20, 0.81], P 5 0.001, I 2 5 0%). TNFi had no significant effect on lumbar spine and hip BMD. Glucocorticoids were associated with a negative effect on lumbar spine (SMD DBMD 20.30 [95% CI 20.55,20.04], P 5 0.02, I 2 5 52%), but not hip BMD. For AS, a significant increase in BMD was seen with TNFi at the lumbar spine (SMD DBMD 0.96 [95% CI 0.64, 1.27], P < 0.001, I 2 5 16%) and hip (SMD DBMD 0.38 [95% CI 0.13, 0.62], P 5 0.003, I 2 5 0%). Data were insufficient to perform meta-analyses in PsA and psoriasis or for other antirheumatic drugs. Conclusion. In RA, TNFi and glucocorticoids appeared to attenuate hand bone loss. TNFi did not impact lumbar spine and hip BMD and glucocorticoids had negative effects on lumbar spine and no effect on hip BMD. In AS, TNFi was associated with improved lumbar spine and hip BMD.

“…Sharp et al cortical porosity (44). The benefit of combining the two has not been demonstrated, nor has the method of determining porosity in the cortex of the metacarpal shaft been described in the detail required to reproduce such measurements.…”

mentioning

confidence: 99%

Denosumab prevents metacarpal shaft cortical bone loss in patients with erosive rheumatoid arthritis

Sharp¹,

Tsuji²,

Ory³

et al. 2010

Objective. Osteoclast-mediated bone loss in the hand predicts future bone erosions in patients with rheumatoid arthritis (RA). Osteoclast activity depends on RANKL, which is inhibited by denosumab, an investigational fully human monoclonal antibody against RANKL. We measured metacarpal shaft cortical bone thickness using a novel computer-based technique, digital x-ray radiogrammetry (DXR), to evaluate the effects of denosumab on cortical bone in RA. Methods. Patients (n ‫؍‬ 227) with active, erosive RA were randomized to receive subcutaneous denosumab 60 mg or 180 mg or placebo every 6 months. All patients received stable doses of methotrexate and daily calcium and vitamin D. For this blinded post hoc analysis (n ‫؍‬ 218), cortical bone loss was determined by DXR using computer-assisted measurement of cortical thickness and shaft width at 21 midshaft levels of the second through fourth metacarpal bones of both hands. Results. At 12 months, patients receiving denosumab had significantly less metacarpal bone loss versus placebo (denosumab 60 mg: ؊0.0034, denosumab 180 mg: 0.0001 gain, placebo: ؊0.0108; P < 0.01 for both denosumab doses). Twelve-month decreases from baseline greater than the smallest detectable change occurred in 2 patients in the denosumab 180 mg group, 9 patients in the denosumab 60 mg group, and 12 patients in the placebo group. Negative correlation was significant between static cortical thickness ratios and static erosion scores (6 and 12 months), and for placebo, between changes in erosion scores and changes in cortical thickness ratio. Conclusion. Twice-yearly injections of denosumab with ongoing methotrexate treatment significantly reduced cortical bone loss in RA patients for up to 12 months. These results add to the growing evidence supporting the clinical utility of DXR.