Glycoprotein YKL-40: A potential biomarker of disease activity in rheumatoid arthritis during intensive treatment with csDMARDs and infliximab. Evidence from the randomised controlled NEO-RACo trial

ObjectiveYKL-40, a chitinase-like glycoprotein associated with inflammation and tissue remodeling, is produced by joint tissues and recognized as a candidate auto-antigen in rheumatoid arthritis (RA). In the present study, we investigated YKL-40 as a potential biomarker of disease activity in patients with early RA at baseline and during intensive treatment aiming for early remission.MethodsNinety-nine patients with early DMARD-naive RA participated in the NEO-RACo study. For the first four weeks, the patients were treated with the combination of sulphasalazine, methotrexate, hydroxychloroquine and low dose prednisolone (FIN-RACo DMARD combination), and subsequently randomized to receive placebo or infliximab added on the treatment for further 22 weeks. Disease activity was evaluated using the 28-joint disease activity score and plasma YKL-40 concentrations were measured by immunoassay.ResultsAt the baseline, plasma YKL-40 concentration was 57 +/- 37 ( mean +/- SD) ng/ml. YKL-40 was significantly associated with the disease activity score, interleukin-6 and erythrocyte sedimentation rate both at the baseline and during the 26 weeks' treatment. The csDMARD combination decreased YKL-40 levels already during the first four weeks of treatment, and there was no further reduction when the tumour necrosis factor-alpha antagonist infliximab was added on the combination treatment.ConclusionsHigh YKL-40 levels were found to be associated with disease activity in early DMARD-naive RA and during intensive treat-to-target therapy. The present results suggest YKL-40 as a useful biomarker of disease activity in RA to be used to steer treatment towards remission

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

Is DAS28 an appropriate tool to assess remission in rheumatoid arthritis?

Objectives: To study which cut off point of DAS28 corresponds to fulfilment of the American Rheumatism Association (ARA) preliminary remission criteria, and clinical remission criteria in patients with rheumatoid arthritis (RA). Methods: All adult patients diagnosed with RA at Jyväskylä Central Hospital 1997–98 were assessed for remission at 5 years. Remission was defined as (a) ARA remission; (b) clinical remission (defined as no tender or swollen joints and normal erythrocyte sedimentation rate). DAS28 was used to measure disease activity. A receiver operating characteristics curve analysis was performed to calculate a cut off point of DAS28 that best corresponds to the ARA remission criteria and the clinical remission criteria. Results: 161 patients (mean age 57 years, 107 (66%) female, 98 (61%) with positive rheumatoid factor, and 51 (32%) with erosions) were studied. At 5 years, 19 (12%) patients met the ARA remission criteria, and 55 (34%) met the clinical remission criteria. The cut off value of DAS28 was 2.32 for the ARA remission criteria, and 2.68 for the clinical remission criteria. In patients with DAS28 <2.32, 11/57 (19%) had tender joints, 6/57 (11%) had swollen joints, and 4/57 (7%) had both tender and swollen joints (66 joint count). Conclusion: In this study the DAS28 cut off point for the ARA remission was lower than in previous studies. The cut off point for DAS28 remission remains controversial. A substantial proportion of patients below the DAS28 cut off point for remission have tender or swollen joints, or both. DAS28 may not be an appropriate tool for assessment of remission in RA

Muscle strength, pain, and disease activity explain individual subdimensions of the Health Assessment Questionnaire disability index, especially in women with rheumatoid arthritis

OBJECTIVE: To study the extent to which muscle strength and performance, pain, and disease activity are associated with the total Health Assessment Questionnaire (HAQ) disability index and its subdimensions in male and female patients with rheumatoid arthritis. METHODS: HAQ for functional capacity was completed by 135 patients with rheumatoid arthritis referred for orthopaedic surgery (74% women; mean (SD) age 62 (10) years; disease duration 19 (13) years, 70% positive for rheumatoid factor). Knee extension, trunk extension and flexion, grip strength, walking speed, and sit‐to‐stand test were measured to mirror physical function. Radiographs of hands and feet, pain, and the modified 28 joint disease activity score (DAS28) were also assessed. RESULTS: Mean total HAQ was 1.08 (0.68) in women and 0.67 (0.70) in men (p = 0.0031). Women had greater disability than men in five of the eight subdimensions of the HAQ. Grip strength was 48%, knee extension strength 46%, trunk extension strength 54%, and trunk flexion strength 43% lower in women than in men. Knee extension strength was inversely correlated with walking time (r = −0.63 (95% confidence interval, −0.73 to −0.51)) and with sit‐to‐stand test (r = −0.47 (−0.60 to −0.31)). In an ordered logistic regression analysis in female rheumatoid patients, DAS28, pain, knee extension strength, and grip strength were associated with the total HAQ disability index. CONCLUSIONS: Women reported greater disability than men both in the total HAQ and in the majority of its eight subdimensions. In addition to disease activity and pain, muscle strength has a major impact on disability especially in female rheumatoid patients

High prevalence of asymptomatic cervical spine subluxation in patients with rheumatoid arthritis waiting for orthopaedic surgery

OBJECTIVE: To study the prevalence of cervical spine subluxation in patients with rheumatoid arthritis waiting for orthopaedic surgery, and symptoms that might be associated with the disorders. METHODS: 194 patients with rheumatoid arthritis were referred for orthopaedic surgery at Jyväskylä Central Hospital, 154 (79%) of whom volunteered for the present study including clinical examination, laboratory tests, radiographs of the cervical spine, hands, and feet, and self report questionnaires. Definition of anterior atlantoaxial subluxation (aAAS) was >3 mm and of subaxial subluxation (SAS) ⩾3 mm. Atlantoaxial impaction (AAI) was analysed following to the Sakaguchi‐Kauppi method. RESULTS: 67 patients (44%) had cervical spine subluxation or previous surgical fusion. The prevalence of aAAS, AAI, SAS, or previous fusion was 27 (18%), 24 (16%), 29 (19%), and 8 (5%), respectively; 69% of patients with cervical spine subluxations (those with fusions excluded) reported neck pain, compared with 65% of patients without subluxations (p = 0.71). The prevalence of occipital, temporal, retro‐orbital, and radicular pain in upper extremities was similar in patients with or without cervical spine subluxations (54% v 43%; 17% v 31%; 25% v 24%; 47% v 48%, respectively). However, patients with subluxations were older, had longer disease duration, more active disease, poorer function according to the Health Assessment Questionnaire, and had more often erosive disease. CONCLUSIONS: Asymptomatic cervical spine subluxation is common in patients with rheumatoid arthritis waiting for orthopaedic surgery. Regardless of symptoms, the possibility of cervical spine subluxation in patients with severe rheumatoid arthritis should be considered in preoperative evaluation

Sustained maintenance of exercise induced muscle strength gains and normal bone mineral density in patients with early rheumatoid arthritis: a 5 year follow up

Objective: To investigate at 5 years whether an initial 2 year home based strength training period imposes sustained effects on muscle strength, bone mineral density (BMD), structural joint damage, and on disease activity in patients with early rheumatoid arthritis (RA). Methods: Seventy patients were randomised either to perform home based strength training with loads of 50–70% of repetition maximum (EG) or range of motion exercises (CG). Both groups were encouraged to take part in aerobic activities 2–3 times a week. Maximal muscle strength of different muscle groups was measured by dynamometers, and BMD at the femoral neck and lumbar spine by dual x ray densitometry. Disease activity was assessed by the 28 joint disease activity score, and joint damage by x ray findings. Results: 62 patients completed 2 years' training and 59 patients attended check up at 5 years. Mean (SD) maximum muscle strength indices increased from baseline to 2 years—in EG from 212 (78) kg by a mean (95% CI) of 68 (55 to 80) and in CG from 195 (72) kg by 35 (13 to 60) kg—and remained at that level for the next 3 years. Development of BMD in EG tended to be more favourable than that in CG. Muscle strength training was not detrimental to joint structures or disease activity. Conclusion: The patients' exercise induced muscle strength gains during a 2 year training period were maintained throughout a subsequent self monitored training period of 3 years. Despite substantial training effects in muscle strength, BMD values remained relatively constant. Radiographic damage remained low even at 5 years

Pain and joint mobility explain individual subdimensions of the health assessment questionnaire (HAQ) disability index in patients with rheumatoid arthritis

Objective: To explore the associations between individual subdimensions of the health assessment questionnaire (HAQ) and clinical variables in patients with rheumatoid arthritis. Methods: 304 patients with rheumatoid arthritis (73% female, mean (SD) age, 58 (13) years; disease duration 6 (9) years, 69% rheumatoid factor positive) completed the HAQ for functional capacity (0–3) and a 100 mm visual analogue scale for pain. Grip strength, range of motion of the large joints, Larsen score for radiographic damage of hand and foot joints, and the number of tender and swollen joints were recorded. A logit regression model was used to study associations between subdimensions of the HAQ and other variables. Results: Mean (range) total HAQ score was 0.92 (0 to 2.88) and varied from 0.73 to 1.04 in the subdimensions. Disability was lowest in the "walking" and highest in the "reach" subdimension. Pain was an explanatory variable in all individual subdimensions. Decreased grip strength, limitation of shoulder and wrist motion, and a larger number of swollen and tender joints in the upper extremities were related to several subdimensions. A higher pain score and swollen joint count in the upper extremities, decreased grip strength, and limited motion of wrist, shoulder, and knee joints explained increased disability (higher total HAQ scores). Conclusions: In patients with rheumatoid arthritis, pain and range of movements of joints have the greatest impact on individual subdimensions of the HAQ. Extent of radiographic damage in peripheral joints and the number of swollen and tender joints are of lesser importance for function