B A C Dijkmans

A matrix risk model for the prediction of rapid radiographic progression in patients with rheumatoid arthritis receiving different dynamic treatment strategies: post hoc analyses from the BeSt study

Objectives To develop a matrix model for the prediction of rapid radiographic progression (RRP) in subpopulations of patients with recent-onset rheumatoid arthritis (RA) receiving different dynamic treatment strategies. Methods Data from 465 patients with recent-onset RA randomised to receive initial monotherapy or combination therapy were used. Predictors for RRP (increase in Sharp-van der Heijde score ≥5 after 1 year) were identified by multivariate logistic regression analysis. For subpopulations, the estimated risk of RRP per treatment group and the number needed to treat (NNT) were visualised in a matrix. Results The presence of autoantibodies, baseline C-reactive protein (CRP) level, erosion score and treatment group were significant independent predictors of RRP in the matrix. Combination therapy was associated with a markedly reduced risk of RRP. The positive and negative predictive values of the matrix were 62% and 91%, respectively. The NNT with initial combination therapy to prevent one patient from RRP with monotherapy was in the range 2–3, 3–7 and 7–25 for patients with a high, intermediate and low predicted risk, respectively. Conclusion The matrix model visualises the risk of RRP for subpopulations of patients with recent-onset RA if treated dynamically with initial monotherapy or combination therapy. Rheumatologists might use the matrix for weighing their initial treatment choice.

Tight control and intensified COBRA combination treatment in early rheumatoid arthritis: 90% remission in a pilot trial

OBJECTIVEnTo investigate the efficacy and feasibility of an intensive combination treatment in early rheumatoid arthritis (RA) combined with monitoring both disease activity and cartilage degradation.nnnMETHODSnIn a pilot trial, 21 patients with active early RA (mean DAS28 5.3; mean disease duration 3 months) were treated with COBRA treatment comprising sulfasalazine, methotrexate and high-dose step-down prednisolone, intensified by adding hydroxychloroquine and continued low-dose prednisolone. In addition, based on measurements of disease activity or a marker of cartilage degradation (CTX-II), treatment adjustments were possible with methotrexate intensification after 8 or 21 weeks; and with infliximab after 21 weeks.nnnRESULTSnNineteen of 21 patients (90%) were in remission (DAS28 <2.6) after 40 weeks (8 weeks, 57%; 21 weeks, 76%). American College of Rheumatology (ACR) criteria, ACR20, 50, 70 and 90 improvements rates were 100%, 95%, 71% and 43% respectively. CTX-II excretion decreased by mean (SD) 347(292) ng/mmol creatinine, but only 50% of patients reduced their CTX-II excretion below the cut-off point. The two monitoring groups showed no significant difference in remission according to DAS score or CTX-II excretion, despite a trend towards more intensive treatment in the CTX-II group. Treatment intensification was feasible according to protocol.nnnCONCLUSIONSnThis small pilot study suggests that intensified and tightly controlled COBRA treatment is uniquely effective in early RA.nnnTRIAL REGISTRATION NUMBERnISRCTN96372677.

HDL protein composition alters from proatherogenic into less atherogenic and proinflammatory in rheumatoid arthritis patients responding to rituximab.

Objective An atherogenic lipid profile is an established risk factor for cardiovascular (CV) diseases. Interestingly, high inflammatory states as present in rheumatoid arthritis (RA) are associated with unfavourable lipid profile. Data about effects of novel immunomodulating agents as rituximab (RTX) on lipid profile are limited. Therefore, changes in lipids in RTX treated RA patients were evaluated. Methods In 49 consecutive RTX treated RA patients, serum and EDTA plasma samples were collected at baseline, 1, 3 and 6 months. In these samples, lipid and levels were assessed to determine changes in time. Surface-enhanced laser desorption/ionisation time-of-flight (SELDI-TOF) MS analysis was performed in six good and six non-responding RA patients to study functional high density lipoprotein (HDL) protein composition changes in time. Results In the total group (n=49), the atherogenic index decreased from 4.3 to 3.9 (∼9%) after 6 months. Testing for effect modification revealed a difference in the effect on lipid levels between responders and non-responders upon RTX (p<0.001). ApoB to ApoA-I ratios decreased significantly (∼9%) in good responding (n=32) patients. SELDI-TOF MS analysis revealed a significant decrease in density of mass charge (m/z) marker 11743, representing a decrease in serum amyloid A, in good responding patients. Conclusion This study indicates beneficial effects on cholesterol profile upon RTX treatment along with improvement of disease activity. Proteomic analysis of the HDL particle reveals composition changes from proatherogenic to a less proatherogenic composition during 6 months RTX treatment. Whether these HDL particle alterations during immunotherapies result in a lower CV event rate remains to be established.

Decreasing incidence of symptomatic gastrointestinal ulcers and ulcer complications in patients with rheumatoid arthritis

Background: Non-steroidal anti-inflammatory drugs (NSAIDs) frequently cause gastrointestinal (GI) ulcers and complications of ulcers. In 1997 in Amsterdam, the incidence of symptomatic GI events was 2.1% (95% CI 1.0–3.1) in patients with rheumatoid arthritis (RA). We conducted a new prospective, observational study on the symptomatic GI events in our outpatient clinics, and compared the data to a previous study conducted by our group. Over the same time period, a decline of GI events over the last decade was reported for US patients. Methods: In 2003, three questionnaires were sent to all RA patients in Amsterdam at 4-month intervals, addressing medication use, dyspepsia, and symptomatic GI events in the previous 4 months. Results: The incidence of GI events in high-risk patients, defined as age ⩾60 and/or history of GI event) using NSAIDs or cyclo-oxygenase 2 specific inhibitors (COXIBs) was 1.2% (95% CI 0.2–2.3), which appears to be substantially lower than the 2.1% observed in 1997; however this difference did not reach statistical significance (pu200a=u200a0.3). In 64% (95% CI 61–68) of the high-risk patients, acid-suppressive drugs (ie, proton pump inhibitors, prostaglandin analogues or high dose H2 antagonists) were used. In 1997 this percentage was significantly lower at 49% (45–52; p<0.001). The compliance to the Dutch guidelines for prevention of NSAID-related gastropathy was almost 75%, with 64% of the patients using acid-suppressive drugs and 11% using COXIBs. Conclusion: The present study reveals a decline of NSAID-induced gastrointestinal events, which is similar to the results observed in the US. This is most likely due to a more strict adherence to guidelines for prevention of NSAID gastropathy, and better treatment of rheumatoid arthritis.

Adverse events in patients with rheumatoid arthritis treated with infliximab in daily clinical practice

Infliximab is highly effective and relatively safe for the treatment of patients with rheumatoid arthritis (RA) in clinical trials.1–5 This prospective cohort study was undertaken to determine adverse events, in particular, infections in patients with RA treated with infliximab in daily clinical practice.nnWe treated 168 patients with RA between 1 April 2000 and 1 October 2002, 82% female, with a median disease duration of 10 years (range 1–49). Inclusion criteria were 28 joint count Disease Activity Score (DAS28) of >3.5 and failure of two disease modifying antirheumatic drugs, including methotrexate. Patients with heart failure or with a malignancy 5 years before screening were excluded. After the alert about tuberculosis,6 patients starting with infliximab treatment were screened for that disease.nnAll patients …

High incidence of cardiovascular events in patients with rheumatoid arthritis

Rheumatoid arthritis (RA) is associated with higher risk for cardiovascular disease (CVD) in comparison with the general population.1 Traditional cardiovascular (CV) risk factors only partially explain the higher risk for CVD.2 There is increasing evidence that inflammation explains the enhanced CV risk in RA, as inflammation has a pivotal role in the development of atherosclerotic disease and this might be the link between increased atherosclerotic CVD and RA.3 Other RA-related factors might be undertreatment of CV comorbidity,1 and the use of non-steroidal anti-inflammatory drugs (NSAIDs) or selective cyclo-oxygenase 2 inhibitors.4,5nnThe objective of this prospective observational study was to determine the incidence of CV events in patients with RA in comparison to the general Dutch population, where the incidence of CV events is …

Risk of post-discharge venous thromboembolism in patients with rheumatoid arthritis undergoing knee or hip arthroplasty. Is prolonged thromboprophylaxis warranted or dangerous?

Venous thromboembolism (VTE)—that is, deep venous thrombosis (DVT) and pulmonary embolism (PE)—are common complications after major hip or knee surgery. Without thromboprophylaxis, the incidence of DVT in patients undergoing major orthopaedic surgery is more than 50%, and fatal PE is reported to occur in 1–6% of these patients.1 These data are based on investigations in which predominantly osteoarthritis (OA) patients were studied. Only a few (small) studies were performed in rheumatoid arthritis (RA) patients: Abernethy reports an incidence of DVT of more than 70% and overall incidence of PE of approximately 2% in RA patients who have undergone a knee arthroplasty,2 and Kelly reports, in his review,3 an incidence of fatal PE of approximately 1% in RA patients undergoing total hip replacement and not receiving thromboprophylaxis (table 1). The risk of developing DVT seems to be similar for RA patients undergoing total hip replacement and those undergoing knee replacement surgery.4nnView this table:nnTable 1 nInhospital venous thromboembolism, without thromboprophylaxis, in major orthopaedic surgery patientsnnnnData are conflicting regarding the risk for developing VTE for RA patients in comparison with OA patients undergoing major orthopaedic surgery. Similar incidences of VTE have been reported for OA patients undergoing major orthopaedic surgery,5 6 whereas one large retrospective study indicated a possibly lower rate of thromboembolic complications in RA patients (table 1).7 In this investigation, inhospital morbidity and mortality of 721 RA patients and 8859 OA patients, who underwent an elective hip replacement operation, were analysed retrospectively. The incidence of thromboembolic events was 0.3% in the RA group versus 1.2% in the OA group (p = 0.07). At first sight, these very low incidences of VTE are remarkable, but they are probably related to a very short observation period and underdiagnosing, by only observing clinical VTE. Hence, the incidence of VTE …

One-year effects of glucocorticoids on bone density: a meta-analysis in cohorts on high and low-dose therapy.

Background Bone loss during glucocorticoid (GC) therapy is poorly quantified. Objective Quantification of bone loss in GC-treated patients with chronic inflammatory diseases (CID; low dose) and transplants (high dose). Methods Meta-analysis of cohorts: PubMed, Cochrane, EMBASE and bibliographic searches (1995–2012). Eligible studies prospectively included GC-treated patients with two dual X-ray absorptiometry measurements of spine or hip over a period of at least 12u2005months. Only supplementation with calcium or vitamin D3 was allowed. 5602 titles yielded 285 articles: 51 study arms in CID (N=1565), 18 study arms in transplantation (N=571). Prednisone-equivalent GC doses and inverse variance weighted mean bone changes were used in a random effects model. Results In CID, the mean GC dose was 8.7u2005mg/day (range 1.2–16.4). The mean 1-year bone loss in the lumbar spine was −1.7% (95% CI –2.2% to –1.2%); in the femoral neck: –1.3 (–1.8 to –0.7). In transplantation, the mean GC dose was 18.9u2005mg/day (range 6.0–52.7). Bone loss in the lumbar spine was −3.6% (–5.2% to –2.0%); in the femoral neck: –3.1% (–5.1% to –1.1%). Within the two groups, bone loss was not related to GC dose. Conclusion In CID, GC-related bone loss appears limited and manageable if current anti-osteoporotic strategies are fully implemented. In transplantation, and probably also other high-dose settings, bone loss is considerable and represents unmet need. The heterogeneity probably reflects the important influence of other factors, most notably the underlying disease and the efficacy of GC treatment.