Clinical experience with the European Ankylosing Spondylitis Infliximab Cohort (EASIC): long-term extension over 7 years with focus on clinical efficacy and safety.

OBJECTIVES: Knowledge on the long-term effects of anti-TNF therapy in patients with ankylosing spondylitis (AS) is still limited. Our objective was to study the long-term efficacy and safety of anti-TNF therapy in AS. METHODS: After having completed the first part of the EASIC trial a total of 71 patients were enrolled into this 96-week extension study. Patients were treated with the same dosages and dosing intervals of infliximab as in the EASIC core study. Efficacy was assessed by using standardised assessment tools such as BASDAI, BASFI, BASMI, patient global assessment, CRP levels and the proportion of patients without any sign of enthesitis or arthritis. Long-term safety was assessed by documenting adverse events (AE), serious adverse events (SAE) and reasons for dropping out. RESULTS: Of the 71 patients included, 64 (90.1%) completed the trial , and 7 discontinued: one was lost to follow-up, 3 withdrew informed consent and in 3 patients therapy was stopped for different reasons: secondary loss of response, recurrent infections and basal cell carcinoma of the skin. The completers showed rather stable low scores of BASDAI (mean 2.4, median 2.52), BASFI (mean 3.1, median 2.76) and BASMI (mean 3.2, median 3) as well as patients global assessment and CRP. The vast majority of patients did not have enthesitis or arthritis. A total of 476 AE were observed, 13 of which were SAE. The majority of these were infections and most of them affected the respiratory tract. Two malignancies occurred: one basal cell carcinoma and one malignant melanoma. These were the only SAE judged to be possibly related to the study drug. CONCLUSIONS: Anti-TNF treatment with infliximab is efficacious over long periods of time in patients with AS. The observation of two skin related malignancies, including one melanoma, during the whole study period of 7 years is in line with reports from previous large AS data sets.

A new curcuma extract (flexofytol®) in osteoarthritis: results from a belgian real-life experience.

This retrospective observational study summarizes the experiences of 820 patients treated with a new Curcuma extract (Flexofytol®, 4-6 capsules per day), for more than 6 months for various forms of painful osteoarthritis. These experiences were reported by 110 Belgian general practitioners via a questionnaire that included quality-of-life parameters for assessing patient experience. Data were submitted to an independent statistician for analysis. Within the first 6 weeks, Flexofytol® improved patient pain, articular mobility, and quality of life. Excellent tolerance was reported, and more than half of these patients were able to discontinue analgaesic and anti-inflammatory drugs. Patient satisfaction was confirmed by their decision to maintain Flexofytol® therapy for more than 6 months. These data must be confirmed with randomized controlled studies. We currently conclude that Flexofytol® which is based on a new preparation of curcumin, is as a potential neutraceutical for the care of patients complaining of joint problems, with excellent tolerance and rapid benefits for articular mobility, pain, and quality of life.

Intra-articular use of a medical device composed of hyaluronic acid and chondroitin sulfate (Structovial CS): effects on clinical, ultrasonographic and biological parameters.

BACKGROUND: This pilot open noncontrolled study was designed to assess the efficacy of intra-articular injections of a solution combining hyaluronic acid (HA) and chondroitin sulphate (CS) in the treatment of outpatients affected by knee osteoarthrosis. FINDINGS: Thirty patients with knee OA have been included. The primary objective was to assess clinical efficacy as measured by pain and Lequesne's index. Secondary objectives were to assess potential effect of the treatment on ultrasound parameters, safety and biomarkers of cartilage metabolism and joint inflammation. After a selection visit (V1), the study treatment was administered 3 times on a weekly basis (V2, V3, V4). Follow-up was planned 6 (V5) and 12 weeks (V6) after the first intra-articular injection. Efficacy results showed a reduction in mean pain at V3 and V6 and in functional impairment, the most marked changes being measured at the two follow-up visits (V5 and V6). Although statistical significance was not achieved due to small sample size, a clear tendency towards improvement was detectable for ultrasound assessments as well as biomarkers. Except for a mild injection site hematoma for which the drug causal relationship could not be excluded, no adverse effect of clinical relevance was recorded during the study. CONCLUSION: Although this pilot study was performed according to an open design only, the ultrasound as well as biomarkers changes strongly suggest a non-placebo effect. These preliminary results call now for a randomized controlled study to confirm the clinical relevance of the observed results. TRIAL REGISTRATION: #ISRCTN91883031.

Yeast as a model system for identification of metabolic targets of a 'glucosamine complex' used as a therapeutic agent of osteoarthritis.

This manuscript describes the effect of a glucosamine complex and its different constituents on the metabolism of yeast cells. Indeed, the yeast model biosystem offers important advantages in the understanding of basic cellular and molecular processes. For example, the possibility to differentiate aerobic and anaerobic metabolism allows the measurement of glycolysis and mitochondria importance in the control of energetic metabolism and stress-responsive. Yeast growth and division can be controlled efficiently and effectively by adjusting environmental conditions that mimic some aspect of those experienced by chondrocytes in an osteoarthritic milieu, such as low oxygen and nutriment availabilities, high oxidative stress, etc. The glucosamine complex or some of its components (glucosamine sulphate, MSM, Ribes nigrum and silicon) enhanced cellular proliferation and CO(2) production of yeast cells cultured under severe conditions. In addition, it allows a larger output of protons from the cells into the medium. Glucosamine complex supplementation also boosted cellular resistance to stresses such as heat shock, H(2)O(2)-induced peroxidation and ethanol. The beneficial effects of the complex were primarily due to R. nigrum and to glucosamine sulphate components. The protective effect of the glucosamine complex can be explained by an increase of cellular energy level through intensification of mitochondrial functionality and intracellular machinery (anaerobic glycolysis). An additional effect on protein kinase activation is not unlikely.

Job of the Bible: leprosy or scabies?

Proposing a medical diagnosis a posteriori of a person who died a long time ago is not as impossible as it sounds if sufficient medical history is available.A whole book of the Bible is devoted to Job and his trials. The diagnosis of leprosy has been generally accepted by medieval commentators because the verses of the Book speak of ulcers disseminated over the skin, and also because leprosy is an exemplary sanction imposed by way of example by God to punish those who have committed a sin. In this paper, we have taken the different verses with a medical content from the Book of Job, and reconstructed the clinical picture as if the patient had turned up in the 21st century in order to see if the diagnosis of leprosy may be called into question, and to discuss the limits of the medico-historic approach. The clinical picture of the disease consists of deterioration in the general condition, with widespread pain, confusion, skin eruptions, bilious vomiting, and so on. Under these conditions, if Job did exist, and if the retrospective medical history is reliable, the most likely diagnosis is that of scabies rather than leprosy.

Open-label, randomized, controlled pilot study of the effects of a glucosamine complex on Low back pain.

BACKGROUND: A series of studies has suggested some efficacy of glucosamine in arthrosis of the knee, but virtually no documentation exists regarding its effects on low back pain. OBJECTIVES: The primary objective of this study was to examine whether a 12-week course of a glucosamine complex (GC) could benefit patients having low back pain despite a course of noninvasive physical therapy. In addition, we sought to delineate the subgroup of responders. METHODS: This open-label, randomized, controlled study was conducted at the Division of Rheumatology and Physical Medicine, Erasme University Hospital, Brussels, Belgium. Male and female outpatients aged 40 to 80 years with low back pain (duration, ≥ 12 weeks; pain score on 10-cm visual analog scale [VAS] [0 = none to 10 = worst imaginable], ≥3 cm) despite noninvasive physical therapy (massage, stretching, heat application, and analgesics for ≥4 weeks) were included. Patients were randomly assigned to receive, in addition to conventional treatment (CT) (physical therapy plus analgesics/antiinflammatories), a GC (enriched with sulfonyl methane, silicon, and a botanical extract of Ribes nigrum) or CT alone (control) for 12 weeks. Pain at rest and on movement (effort) and early morning lumbar stiffness were measured every 4 weeks using the VAS. The primary end point was improvement in VAS score for pain at rest at 12 weeks. Two validated questionnaires were used to assess improvements in quality of life (QOL) (Oswestry Disability Questionnaire [ODQ] [10 items; scale: 0 = no disability to 60 = maximal disability] and Roland-Morris Disability Questionnaire [RMDQ] [24 items; scale: 0 = no disability to 24 = severe disability]). Responders were defined as patients who positively assessed the efficacy of the GC. At each visit, patients were also asked about possible adverse events. RESULTS: Of 36 enrolled patients, 32 completed the study (18 men, 14 women; mean [SE] age, 64 [2] years; 17 in the GC group and 15 in the control group). Four patients were lost to follow-up. At week 4, changes from baseline VAS scores for pain at rest and lumbar stiffness were significantly greater in the GC group compared with the control group (P < 0.001 and P = 0.011, respectively). At week 4, QOL was found to be improved, as measured using the ODQ, in the GC group compared with the control group (P = 0.028), but the between-group difference as measured using the RMDQ was not significant. The improvements from baseline on the questionnaires were sustained over the 12-week period in the GC group (all, P < 0.001). Gastrointestinal adverse effects were reported by 1 GC-treated patient and 1 patient in the control group, but neither patient withdrew from the study. Of the 17 GC-treated patients, 9 considered themselves responders, but the profile of a responder could not be delineated. CONCLUSIONS: In this study in patients with low back pain, analgesic effect and improvement in QOL were found with the use of GC. GC was well tolerated.

Sonography detection threshold for knee effusion.

The aim of this study was to determine the threshold for detecting knee effusion by ultrasound (US). Five knee specimens from embalmed cadavers were studied. Intra-articular injection of saline, blood and synovial fluid was performed under ultrasound control and methylene blue dye instillation. The smallest amount of fluid detectable by US in the knee was 7.4 ml for synovial fluid, 10.1 and 10.4 ml for saline solution and 9.7 for blood. The threshold for detecting knee joint effusion by US in cadaver specimens was 10 ml for saline and blood and 7 ml for synovial fluid.

Abnormalities in the replicative capacity of osteoblastic cells in the proximal femur of patients with osteonecrosis of the femoral head.

OBJECTIVE: Aseptic nontraumatic osteonecrosis (ON) of the femoral head is a painful disorder that often leads to femoral head collapse due to subchondral fracture. We postulated that alteration of osteoblast function might play a role in the pathophysiology of ON. We evaluated the ex vivo proliferation rate and differentiation capacity of osteoblasts derived from the intertrochanteric region of the femur and of the iliac crest of patients with ON of the femoral head and compared it with patients with hip osteoarthritis (OA). METHODS: We examined the function of osteoblastic cells in cultures derived from bone biopsies of the intertrochanteric region of the femur and of the iliac crest obtained from 13 patients with ON of the femoral head and 8 patients with hip OA. The replicative capacity was assessed by the proliferation rate in secondary culture. The phenotypic characterization was evaluated by the level of alkaline phosphatase activity, the sensitivity to 1,25 (OH)2 vitamin D3, and collagen synthesis. RESULTS: The replicative capacity of the osteoblastic cells of the intertrochanteric area of the femur in ON patients was significantly reduced compared to patients with OA. The capacity of differentiation, however, was not different between ON and OA patients. CONCLUSION: The replicative capacity of osteoblastic cells is significantly reduced in the femur of patients with ON. Our results confirm that altered osteoblastic function plays a role in the pathophysiology of ON of the femoral head.

Infliximab in primary Sjögren's syndrome: one-year followup.

OBJECTIVE: To evaluate the safety and efficacy of a maintenance regimen of infliximab in patients with active primary Sjögren's syndrome (SS) over a 1-year period. METHODS: This followup study included 10 of the 16 patients with primary SS who participated in a pilot study. Patients who continued to have symptoms received additional infusions of infliximab for 1 year. RESULTS: All patients completed the 1-year followup for evaluation of efficacy. After 1 year, a statistically significant decrease in global and local disease manifestations was observed in all 10 patients. Treatment was generally well tolerated, with the main side effect being a mild, self-limited infusion reaction. CONCLUSION: Sustained improvement of active primary SS may be possible with infliximab treatment.

Costimulatory blockade in patients with rheumatoid arthritis: a pilot, dose-finding, double-blind, placebo-controlled clinical trial evaluating CTLA-4Ig and LEA29Y eighty-five days after the first infusion.

OBJECTIVE: T cells are involved in the pathogenesis of rheumatoid arthritis (RA). In animal models of autoimmune diseases, blockade of costimulatory molecules on antigen-presenting cells has been demonstrated to be effective in preventing or treating this disease by preventing T cell activation. To date, the effect of costimulatory blockade in patients with RA is unknown. The goal of this multicenter, multinational study was to determine the safety and preliminary efficacy of costimulatory blockade using CTLA-4Ig and LEA29Y in RA patients who have been treated unsuccessfully with at least 1 disease-modifying agent. METHODS: CTLA-4Ig, LEA29Y (0.5, 2, or 10 mg/kg), or placebo was administered intravenously to 214 patients with RA. Patients received 4 infusions of study medication, on days 1, 15, 29, and 57, and were evaluated on day 85. The primary end point was the proportion of patients meeting the American College of Rheumatology 20% improvement criteria (ACR20). All patients were monitored for treatment safety and tolerability. RESULTS: CTLA-4Ig and LEA29Y infusions were well tolerated at all dose levels. Peri-infusional adverse events were carefully monitored, and showed similar incidence across all dose groups with the exception of headaches, which were slightly more frequent in the 2 treatment groups. The incidence of discontinuations due to worsening of RA was 19%, 12%, and 9% at 0.5, 2, and 10 mg/kg, respectively, in the CTLA-4Ig-treated patients and 3%, 3%, and 6% at 0.5, 2, and 10 mg/kg, respectively, in the LEA29Y-treated patients (versus 31% in the placebo group). ACR20 responses on day 85 had increased in a dose-dependent manner (23%, 44%, and 53% of CTLA-4Ig-treated patients and 34%, 45%, and 61% of LEA29Y-treated patients at 0.5, 2.0, and 10 mg/kg, respectively, versus 31% of placebo-treated patients). CONCLUSION: Both of the costimulatory blocking molecules studied were generally safe and well tolerated. As compared with placebo, both CTLA-4Ig and LEA29Y demonstrated efficacy in the treatment of RA.

Infecton is not specific for bacterial osteo-articular infective pathology.

The aim of this study was to re-examine, by retrospective analysis of our case material, the specificity and sensitivity of technetium-99m ciprofloxacin scan in discriminating between infection and other conditions. (99m)Tc-ciprofloxacin scintigraphy was performed in 71 patients: 30 patients referred for suspicion of osteomyelitis (OM) or septic arthritis (SA) (group 1) and 41 controls (group 2). Imaging was performed at 4 h post injection and, when possible, at 8 or 24 h post injection. Tracer uptake was visually assessed in different joint groups, and in the sites suspicious for infection. Several soft tissue sites were also evaluated. In the group referred for osteo-articular infection, we found a lower specificity (54.5%) than has previously been reported in the literature. Evaluation of tracer uptake at late imaging did not improve discrimination between sterile and non-sterile inflammation. Additionally, articular uptake was seen in many control patients. Infecton uptake in growth cartilage, thyroid gland, vascular pool, lungs, liver and intestines is discussed.