Boulos Haraoui

Treating rheumatoid arthritis to target: recommendations of an international task force

Background Aiming at therapeutic targets has reduced the risk of organ failure in many diseases such as diabetes or hypertension. Such targets have not been defined for rheumatoid arthritis (RA). Objective To develop recommendations for achieving optimal therapeutic outcomes in RA. Methods A task force of rheumatologists and a patient developed a set of recommendations on the basis of evidence derived from a systematic literature review and expert opinion; these were subsequently discussed, amended and voted upon by >60 experts from various regions of the world in a Delphi-like procedure. Levels of evidence, strength of recommendations and levels of agreement were derived. Results The treat-to-target activity resulted in 10 recommendations. The treatment aim was defined as remission with low disease activity being an alternative goal in patients with long-standing disease. Regular follow-up (every 1–3 months during active disease) with appropriate therapeutic adaptation to reach the desired state within 3 to a maximum of 6 months was recommended. Follow-up examinations ought to employ composite measures of disease activity which include joint counts. Additional items provide further details for particular aspects of the disease. Levels of agreement were very high for many of these recommendations (≥9/10). Conclusion The 10 recommendations are supposed to inform patients, rheumatologists and other stakeholders about strategies to reach optimal outcomes of RA based on evidence and expert opinion.

Treating Rheumatoid Arthritis to Target: A Canadian Physician Survey

Objective. To assess agreement and application of Treat to Target (T2T) recommendations in Canadian practice. Methods. A survey of Canadian rheumatologists was conducted on the recommendations of T2T, an international initiative toward reaching specific therapeutic goals in rheumatoid arthritis. Agreement with each recommendation was measured on a 10-point Likert scale (1 = fully disagree, 10 = fully agree). A 4-point Likert scale (never, not very often, very often, always) assessed application of each recommendation in current practice. Responders who answered “never” or “not very often” were asked whether they were willing to change their practice according to the particular recommendation. Results. Seventy-eight rheumatologists responded (24% of the 330 who were contacted). The average agreement scores ranged from 6.92 for recommendation #5 (the frequency of measures of disease activity) to 9.10 for recommendation #10 (the patient needs to be involved in the decision-making process). A majority of participants indicated that they apply the T2T recommendations in their practice. Recommendations dealing with frequency of visits and the use of composite measures received the highest number of “never” or “not very often” responses. Busy practices and lack of confidence in composite outcome measures were the main reasons for objections to certain components of the recommendations. Conclusion. Although a majority of Canadian rheumatologists agreed with and supported the T2T recommendations, there was resistance toward specific aspects of these recommendations. Efforts are needed to better understand the reasons behind identified disagreements. Action plans to encourage the application of T2T recommendations in Canada are in development.

Treating rheumatoid arthritis to target: 2014 update of the recommendations of an international task force

Background Reaching the therapeutic target of remission or low-disease activity has improved outcomes in patients with rheumatoid arthritis (RA) significantly. The treat-to-target recommendations, formulated in 2010, have provided a basis for implementation of a strategic approach towards this therapeutic goal in routine clinical practice, but these recommendations need to be re-evaluated for appropriateness and practicability in the light of new insights. Objective To update the 2010 treat-to-target recommendations based on systematic literature reviews (SLR) and expert opinion. Methods A task force of rheumatologists, patients and a nurse specialist assessed the SLR results and evaluated the individual items of the 2010 recommendations accordingly, reformulating many of the items. These were subsequently discussed, amended and voted upon by >40 experts, including 5 patients, from various regions of the world. Levels of evidence, strengths of recommendations and levels of agreement were derived. Results The update resulted in 4 overarching principles and 10 recommendations. The previous recommendations were partly adapted and their order changed as deemed appropriate in terms of importance in the view of the experts. The SLR had now provided also data for the effectiveness of targeting low-disease activity or remission in established rather than only early disease. The role of comorbidities, including their potential to preclude treatment intensification, was highlighted more strongly than before. The treatment aim was again defined as remission with low-disease activity being an alternative goal especially in patients with long-standing disease. Regular follow-up (every 1–3 months during active disease) with according therapeutic adaptations to reach the desired state was recommended. Follow-up examinations ought to employ composite measures of disease activity that include joint counts. Additional items provide further details for particular aspects of the disease, especially comorbidity and shared decision-making with the patient. Levels of evidence had increased for many items compared with the 2010 recommendations, and levels of agreement were very high for most of the individual recommendations (≥9/10). Conclusions The 4 overarching principles and 10 recommendations are based on stronger evidence than before and are supposed to inform patients, rheumatologists and other stakeholders about strategies to reach optimal outcomes of RA.

Meniscal tear and extrusion are strongly associated with progression of symptomatic knee osteoarthritis as assessed by quantitative magnetic resonance imaging

Background: The relation between knee meniscal structural damage and cartilage degradation is plausible but not yet clearly proven. Objectives: To quantitate the cartilage volume changes in knee osteoarthritis using magnetic resonance imaging (MRI), and determine whether meniscal alteration predicts cartilage volume loss over time. Methods: 32 patients meeting ACR criteria for symptomatic knee osteoarthritis were studied. MRI knee acquisitions were done every six months for two years. The cartilage volumes of different knee regions were measured. Three indices of structural change in the medial and lateral menisci were evaluated—degeneration, tear, and extrusion—using a semiquantitative scale. Results: 24 patients (75%) had mild to moderate or severe meniscal damage (tear or extrusion) at baseline. A highly significant difference in global cartilage volume loss was observed between severe medial meniscal tear and absence of tear (mean (SD), −10.1 (2.1)% v −5.1 (2.4)%, p = 0.002). An even greater difference was found between the medial meniscal changes and medial compartment cartilage volume loss (−14.3 (3.0)% in the presence of severe tear v −6.3 (2.7)% in the absence of tear; p<0.0001). Similarly, a major difference was found between the presence of a medial meniscal extrusion and loss of medial compartment cartilage volume (−15.4 (4.1)% in the presence of extrusion v −4.5 (1.7)% with no extrusion; p<0.001). Conclusions: Meniscal tear and extrusion appear to be associated with progression of symptomatic knee osteoarthritis.

Evidence for treating rheumatoid arthritis to target: results of a systematic literature search update

Objective A systematic literature review (SLR; 2009–2014) to compare a target-oriented approach with routine management in the treatment of rheumatoid arthritis (RA) to allow an update of the treat-to-target recommendations. Methods Two SLRs focused on clinical trials employing a treatment approach targeting a specific clinical outcome were performed. In addition to testing clinical, functional and/or structural changes as endpoints, comorbidities, cardiovascular risk, work productivity and education as well as patient self-assessment were investigated. The searches covered MEDLINE, EMBASE, Cochrane databases and Clinicaltrial.gov for the period between 2009 and 2012 and separately for the period of 2012 to May of 2014. Results Of 8442 citations retrieved in the two SLRs, 176 articles underwent full-text review. According to predefined inclusion/exclusion criteria, six articles were included of which five showed superiority of a targeted treatment approach aiming at least at low-disease activity versus routine care; in addition, publications providing supportive evidence were also incorporated that aside from expanding the evidence provided by the above six publications allowed concluding that a target-oriented approach leads to less comorbidities and cardiovascular risk and better work productivity than conventional care. Conclusions The current study expands the evidence that targeting low-disease activity or remission in the management of RA conveys better outcomes than routine care.

The effects of tumour necrosis factor inhibitors, methotrexate, non-steroidal anti-inflammatory drugs and corticosteroids on cardiovascular events in rheumatoid arthritis, psoriasis and psoriatic arthritis: a systematic review and meta-analysis

The objective of this systematic literature review was to determine the association between cardiovascular events (CVEs) and antirheumatic drugs in rheumatoid arthritis (RA) and psoriatic arthritis (PsA)/psoriasis (Pso). Systematic searches were performed of MEDLINE, EMBASE and Cochrane databases (1960 to December 2012) and proceedings from major relevant congresses (2010-2012) for controlled studies and randomised trials reporting confirmed CVEs in patients with RA or PsA/Pso treated with antirheumatic drugs. Random-effects meta-analyses were performed on extracted data. Out of 2630 references screened, 34 studies were included: 28 in RA and 6 in PsA/Pso. In RA, a reduced risk of all CVEs was reported with tumour necrosis factor inhibitors (relative risk (RR), 0.70; 95% CI 0.54 to 0.90; p=0.005) and methotrexate (RR, 0.72; 95% CI 0.57 to 0.91; p=0.007). Non-steroidal anti-inflammatory drugs (NSAIDs) increased the risk of all CVEs (RR, 1.18; 95% CI 1.01 to 1.38; p=0.04), which may have been specifically related to the effects of rofecoxib. Corticosteroids increased the risk of all CVEs (RR, 1.47; 95% CI 1.34 to 1.60; p<0.001). In PsA/Pso, systemic therapy decreased the risk of all CVEs (RR, 0.75; 95% CI 0.63 to 0.91; p=0.003). In RA, tumour necrosis factor inhibitors and methotrexate are associated with a decreased risk of all CVEs while corticosteroids and NSAIDs are associated with an increased risk. Targeting inflammation with tumour necrosis factor inhibitors or methotrexate may have positive cardiovascular effects in RA. In PsA/Pso, limited evidence suggests that systemic therapies are associated with a decrease in all CVE risk.

Long term evaluation of disease progression through the quantitative magnetic resonance imaging of symptomatic knee osteoarthritis patients: correlation with clinical symptoms and radiographic changes.

The objective of this study was to further explore the cartilage volume changes in knee osteoarthritis (OA) over time using quantitative magnetic resonance imaging (qMRI). These were correlated with demographic, clinical, and radiological data to better identify the disease risk features. We selected 107 patients from a large trial (n = 1,232) evaluating the effect of a bisphosphonate on OA knees. The MRI acquisitions of the knee were done at baseline, 12, and 24 months. Cartilage volume from the global, medial, and lateral compartments was quantified. The changes were contrasted with clinical data and other MRI anatomical features. Knee OA cartilage volume losses were statistically significant compared to baseline values: -3.7 ± 3.0% for global cartilage and -5.5 ± 4.3% for the medial compartment at 12 months, and -5.7 ± 4.4% and -8.3 ± 6.5%, respectively, at 24 months. Three different populations were identified according to cartilage volume loss: fast (n = 11; -13.2%), intermediate (n = 48; -7.2%), and slow (n = 48; -2.3%) progressors. The predictors of fast progressors were the presence of severe meniscal extrusion (p = 0.001), severe medial tear (p = 0.005), medial and/or lateral bone edema (p = 0.03), high body mass index (p < 0.05, fast versus slow), weight (p < 0.05, fast versus slow) and age (p < 0.05 fast versus slow). The loss of cartilage volume was also slightly associated with less knee pain. No association was found with other Western Ontario McMaster Osteoarthritis Index (WOMAC) scores, joint space width, or urine biomarker levels. Meniscal damage and bone edema are closely associated with more cartilage volume loss. These data confirm the significant advantage of qMRI for reliably measuring knee structural changes at as early as 12 months, and for identifying risk factors associated with OA progression.

Canadian Rheumatology Association Recommendations for Pharmacological Management of Rheumatoid Arthritis with Traditional and Biologic Disease-modifying Antirheumatic Drugs

Objective. The Canadian Rheumatology Association (CRA) has developed recommendations for the pharmacological management of rheumatoid arthritis (RA) with traditional and biologic disease-modifying antirheumatic drugs (DMARD) in 2 parts. Part 1 is reported here. Methods. The CRA Therapeutics Committee assembled a national working group of RA clinical experts, researchers, patient consumers, and a general practitioner. Treatment questions were developed a priori based on results of a national needs assessment survey. A systematic review of all clinical practice guidelines and consensus statements regarding treatment with traditional and biologic DMARD in patients with RA published between January 2000 and June 2010 was performed in Medline, Embase, and CINAHL databases, and the grey literature. Guideline quality was assessed by 2 independent reviewers, and guideline characteristics, recommendations, and supporting evidence from observational studies and randomized controlled trials were synthesized into evidence tables. The full working group reviewed the evidence tables and developed recommendations using a modified Delphi technique. Results. Five overarching principles and 26 recommendations addressing general RA management strategies and treatment with glucocorticoids and traditional and biologic DMARD were developed for rheumatologists, other primary prescribers of RA drug therapies, and patients with RA. Conclusion. These recommendations were developed based on a synthesis of international guidelines, supporting evidence, and expert consensus considering the Canadian healthcare context with the intention of promoting best practices and improving healthcare delivery for persons with RA.

Risk factors associated with the loss of cartilage volume on weight-bearing areas in knee osteoarthritis patients assessed by quantitative magnetic resonance imaging: a longitudinal study

The objective of this study was to identify, on a symptomatic knee osteoarthritis (OA) cohort, the risk factors associated with the progression of the disease. More specifically, we investigated the correlation between knee cartilage volume loss from subregions over the span of 24 months by means of quantitative magnetic resonance imaging (qMRI) with demographic, clinical, radiological, and MRI structural changes.A cohort of 107 patients with knee OA selected from a large trial evaluating the effect of a bisphosphonate underwent x-rays and MRI of the knee at baseline and 24 months. Joint space width (JSW) and joint space narrowing (JSN) and cartilage volume loss over time in subregions of the tibial plateaus and femoral condyles were quantitated. Structural changes in the subchondral bone (hypersignal) and in the menisci (tear and extrusion) were also evaluated.The greatest cartilage volume loss was found in the medial compartment, and risk factors included female gender, JSW, meniscal lesions, and bone changes at baseline. Subregion analysis revealed that the greatest cartilage volume loss at 24 months was found in the central area of the medial tibial plateau (15%; p < 0.0001) and of the medial femoral condyle (12%; p < 0.0001). These findings were associated with the presence at baseline of meniscal extrusion, particularly severe meniscal extrusion, medial and severe meniscal tear, bone hypersignal, high body mass index (BMI), smaller JSW, increases in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain and patient global scores over time, and greater JSN. Parameters predicting medial central femoral condyle cartilage volume loss at 24 months were lateral meniscal tear, SF-36 and BMI at baseline, and JSN. At the medial central tibial plateau, the parameters were severe meniscal extrusion, severe lateral meniscal tear, and bone hypersignal in the lateral compartment at baseline, and WOMAC pain change.Meniscal damage and bone changes are the features most closely associated with the greatest subregional cartilage volume loss. Interestingly, for the first time, JSN was strongly associated with cartilage loss in the central areas of plateaus and condyles. This study also further confirms the correlation between cartilage volume loss and JSN and symptomatic changes at 24 months.

Correlation between bone lesion changes and cartilage volume loss in patients with osteoarthritis of the knee as assessed by quantitative magnetic resonance imaging over a 24-month period

Objective: To evaluate in patients with knee osteoarthritis (OA) the size changes in bone oedema and cysts over 24 months, and to contrast these changes with cartilage volume loss using quantitative magnetic resonance imaging. Methods: 107 patients with knee OA, selected from a large trial evaluating the effect of a bisphosphonate, were analysed by magnetic resonance imaging at baseline and 24 months. Assessments of subchondral bone oedema and cysts, and cartilage volume were done. Results: At baseline, 86 patients showed the presence of at least one type of bone lesion: 71 oedema, 61 cysts and 51 both. At 24 months, although not statistically significant, the oedema total size change increased by 2.09 (SD 15.03) mm, and the cyst by 1.09 (8.13) mm; mean size change for the oedema was +0.38 (2.18) mm and −0.10 (4.36) mm for the cyst. When analysed according to subregions, an increase was found for the cyst size in the trochlea (+0.67 (2.74) mm, p = 0.02) and in the lateral tibial plateau (+0.15 (0.83) mm, p = 0.09), and for the oedema size in the medial tibial plateau (+1.73 (8.11) mm, p = 0.05). At 24 months, significant correlations were seen between the loss of cartilage volume and oedema size change in the medial condyle (−0.40, p = 0.0001) and the medial tibial plateau (−0.23, p = 0.03), and the changes in cyst size in the medial condyle (−0.29, p = 0.01). A multivariate analysis showed that the oedema size change was strongly and independently associated with medial cartilage volume loss (−0.31, p = 0.0004). Conclusion: These data demonstrate that bone lesions are prevalent in knee OA. The correlation of the oedema and cyst size increase in the medial compartment over time with a greater loss of cartilage volume in this area underlines the importance of subchondral bone lesions in OA pathophysiology.