These findings were constant when the response to treatment was evaluated after 3 or 7?months of treatment (fig 2?2).). to 2.1) (median (interquartile range (IQR))) and a CRP 15?mg/l (IQR: 9 to 24). The sRANKL levels and RANKL/OPG ratio in patients that achieved remission were significantly lower at baseline than in the remaining patients at both 3 and 7?months Hoxa of follow\up. The sOPG levels correlated with the HAQ and the physician’s disease assessment and diminished significantly after a\TNF treatment. However, no significant association was detected between the therapeutic response profile and sOPG levels. Conclusions These data suggest that in patients receiving a\TNF treatment, lower serum levels of RANKL and RANKL/OPG ratio may serve to predict remission. In rheumatoid arthritis (RA), bone destruction in the erosions is mainly due to the abnormal activation of osteoclasts. It is currently known that the control of osteoclast formation and activation is principally mediated by three components of the TNF signalling pathway: the receptor activator for nuclear factor kappaB (RANK), a membrane\bound osteclast receptor that initiates osteclastic bone resorption after binding its ligand (RANKL) and osteoprotegerin (OPG), the key inhibitor of bone resorption that acts as a soluble, non\signalling decoy receptor for RANKL.1 Therefore, the balance between OPG and RANKL is a fundamental factor in controlling bone resorption and can be influenced by several hormones and cytokines, including TNF. Soluble OPG and RANKL can be measured in human serum, and higher levels of these mediators have been described in serum samples from RA patients when compared with healthy individuals.2 Moreover, higher levels of RANKL are also expressed in tissues from patients with active RA and spondyloarthropathies than in tissues from patients with inactive RA or osteoarthritis and from normal subjects.3 Given the success of TNF blockade in preventing structural damage in RA, some recent studies have focused on the effect of a\TNF therapies on the soluble or tissue levels of RANKL and OPG.2,4,5 However, to date, there are still no data to indicate the value of the levels of these proteins in predicting the therapeutic response. The aim of the present study was to investigate the utility of serum (s)RANKL and sOPG to predict a therapeutic response to a\TNF. Patients and methods Patients The characteristics of the patients included in this study are summarised in table 1?1,, and all of them fulfilled the 1988 RA classification criteria.6 Patients treated with adalimumab (ADA) were those enrolled in the clinical trial ReAct at our three hospitals, while those treated with infliximab (INF) were consecutive patients from our daily clinical practice. Serum samples Xyloccensin K were obtained prior to commencing the a\TNF treatment (baseline), and a second sample (final) was obtained either at week 12 in patients treated with ADA or prior to the 4th infusion (week 14) in those treated with INF. The laboratory and clinical information for each patient was obtained from clinical records at baseline, 3?months (week 12 (ADA) and 14 (INF)) and 7?months (week 28 (ADA) and 30 (INF)). All patients gave their informed written and signed consent. Table 1?Patient characteristics
Number756510CFemale n (%)61 (81.3)51 (78.5)10 (100)NS*Age (years)56 (14)57 (14)50 (14)NS?Disease duration (years)8 (4C15)8.5 (4C15)7.5 (6C24)NS?RF positive n (%)65 (86.7)58 (89.2)7 (70)NS*DAS28 baseline5.9 (1)5.9 (1.1)6 (1)NS?HAQ baseline1.6 (1.1C2.1)1.6 (1.1C2.3)1.6 (1.3C2)NS?Ph\GDA baseline61 (16)60 (15)70 (19)0.06?CRP baseline (g/l)15 (9C24)15 (8C22)27 (11C42)0.05?Clinical response n (%)62 (82.7)55 (84.6)7 (70)NS*Remission (%)10 (13.3)8 (12.3)2 (20)NS* Open in a separate window *2 test; ?t test; ?MannCWhitney test. RF, rheumatoid factor; DAS28, 28 joint count disease Xyloccensin K activity score; Ph\GDA, physician’s global disease assessment; CRP, C\reactive protein. The response to treatment at the analysed visits was classified as remission (DAS28<2.6), clinical response Xyloccensin K without remission (a decrease in DAS28?1.2 respect baseline visit) and no response (a decrease in DAS28<1.2 respect baseline visit). Measurement of RANKL and OPG in serum Serum OPG and RANKL levels were assessed (blind testing) using a commercially available enzyme\linked immunoabsorbent assay from R&D Systems (Minneapolis, MN) and Immundiagnostik/Apotech (Epalinges, Switzerland), respectively. The coefficients.