Evidence-based multimodal conservative treatment using a standardized protocol for knee and/or hip OA is feasible and successful in 47% of patients. In general, response could not be predicted. Basic first-line recommended conservative treatment options have not been used adequately prior to referral to secondary care in the vast majority of patients.

Important levels of fatigue are common in knee and hip OA patients. After evidence-based tailored conservative treatment targeted to improve pain and physical function, a small decrease in fatigue levels was found. Reduction in levels of different fatigue dimensions were related to the change in physical function and pain.

s u m m a r yObjective: To explore the associations between different histologically assessed, inflammatory synovial characteristics and subsequent clinical and structural aspects in knee osteoarthritis (OA). Design: Knee OA patients, ranging in stage from early to advanced, were recruited from three different ongoing studies. Synovial tissue biopsies were taken and histologically assessed for six features (four inflammatory related aspects, fibrosis and fibrin deposition). Clinical aspects (WOMAC pain, functioning and stiffness and SF-36 vitality) and structural aspects (Kellgren and Lawrence (KL)-grade, joint space narrowing (JSN; 0e3) and osteophytes (0e3), and reception of total knee replacement (TKR)) were repeatedly assessed during follow-up. Associations between histology and clinical and structural aspects were analysed using linear mixed model analyses and cox proportional hazards analysis. Results: Biopsies of 83 patients (median complaint duration: 5 [2e8] years) were analysed. Follow-up was a median of 1.4 [0.8e2.7] years for clinical and 1.8 [0.2e5.2] years for structural aspects. Fibrosis and fibrin deposition were inversely correlated with the inflammatory features. A higher fibrosis score was associated with a lower scores for KL-grade, JSN and osteophytes, while higher scores for perivascular oedema, synovial lining thickness and vascularisation were associated with higher scores for structural aspects during follow-up. No associations were found between each of the histological features and any of the clinical aspects or the chance for TKR during follow-up. Conclusions: Inflammatory related histological aspects are associated with subsequent increased radiological severity in knee OA, while fibrosis seems to protect against this, providing a potential therapeutic target for OA treatment.

Infliximab dosages of 5 mg/kg can be lowered in the majority of patients with RA using DAS28-guided dose titration without increase of disease activity. Lowering the dose of infliximab should be considered in every patient receiving higher doses infliximab.

Objectives Evidence suggests that doxycycline might have disease-modifying properties in osteoarthritis. However, the clinically relevant question as to whether doxycycline also modifi es symptoms in knee osteoarthritis is unanswered. The objective of this study was to investigate the effectiveness of doxycycline on pain and daily functioning in symptomatic knee osteoarthritis. Methods A 24-week, randomised, triple-blind, placebo controlled trial on the symptomatic effectiveness of doxycycline twice a day 100 mg in knee osteoarthritis patients according to the clinical and radiological American College of Rheumatology classifi cation criteria. The primary endpoint was the difference in the proportion of participants in both study groups achieving a clinical response defi ned by the OMERACT-OARSI set of responder criteria. Secondary endpoints included pain, stiffness, daily functioning, patient global assessment, quality of life, osteoarthritis-related medication and side effects. Results 232 patients were randomly assigned. At study end, 31% of participants met the primary endpoint in both groups. Except for more adverse events in the doxycycline group, no differences were also found on the secondary endpoints. Conclusions Doxycycline is not effective in reducing symptoms in knee osteoarthritis patients over a 24-week study period, but is associated with an increased risk of adverse events. Although a possible structure-modifying effect of doxycycline was previously suggested, this is not accompanied by symptom relief in the short and medium term. Dutch Trial Register no NTR1111.The search for a disease-modifying osteoarthritis drug (DMOAD) for osteoarthritis targeting both symptoms and structure has been intensifi ed in recent years. Several studies investigating candidate DMOAD in clinical trials have been published, including dietary supplements, diacerein, strontium ranalate, bisphosphonates, biological agents, autologous conditioned serum, calcitonin and doxycycline. 1 -18 However, up to now, no agent is known to be an irrefutable confi rmed DMOAD as results of most studies remain largely ambiguous or diffi cult to interpret. For diacerein, risedronate, calcitonin and autologous conditioned serum the effi cacy on symptoms have been demonstrated in randomised controlled trials, but these results have thus far not been confi rmed in more than one study, except for diacerein. Effects on structural change have been shown for risedronate, diacerein and doxycycline, 5 12 13 although these results have not been replicated successfully thus far. 19 Whether doxycycline also modifi es symptoms of osteoarthritis has not yet been established. Doxycycline is a tetracycline class antibiotic agent. Besides being an antimicrobial agent, it is a metalloproteinase inhibitor and inhibits the collagenase that cleaves collagen type IX that is present in articular cartilage. 20 -22 Doxycycline has been studied in human osteoarthritis in one clinical trial, in which doxycycline was found to retard the progression of ra...