EULAR evidence based recommendations for the management of hip osteoarthritis: report of a task force of the EULAR Standing Committee for International Clinical Studies Including Therapeutics (ESCISIT)

OBJECTIVE: To develop evidence based recommendations for the management of hip osteoarthritis (OA). METHODS: The multidisciplinary guideline development group comprised 18 rheumatologists, 4 orthopaedic surgeons, and 1 epidemiologist, representing 14 European countries. Each participant contributed up to 10 propositions describing key clinical aspects of hip OA management. Ten final recommendations were agreed using a Delphi consensus approach. Medline, Embase, CINAHL, Cochrane Library, and HTA reports were searched systematically to obtain research evidence for each proposition. Where possible, outcome data for efficacy, adverse effects, and cost effectiveness were abstracted. Effect size, rate ratio, number needed to treat, and incremental cost effectiveness ratio were calculated. The quality of evidence was categorised according to the evidence hierarchy. The strength of recommendation was assessed using the traditional A-D grading scale and a visual analogue scale. RESULTS: Ten key treatment propositions were generated through three Delphi rounds. They included 21 interventions, such as paracetamol, NSAIDs, symptomatic slow acting disease modifying drugs, opioids, intra-articular steroids, non-pharmacological treatment, total hip replacement, osteotomy, and two general propositions. 461 studies were identified from the literature search for the proposed interventions of efficacy, side effects, and cost effectiveness. Research evidence supported 15 interventions in the treatment of hip OA. Evidence specific for the hip was strikingly lacking. Strength of recommendation varied according to category of research evidence and expert opinion. CONCLUSION: Ten key recommendations for the treatment of hip OA were developed based on research evidence and expert consensus. The effectiveness and cost effectiveness of these recommendations were evaluated and the strength of recommendation was scored.     

Valdecoxib is as effective as diclofenac in the management of rheumatoid arthritis with a lower incidence of gastroduodenal ulcers: results of a 26-week trial

OBJECTIVE: To compare the efficacy and upper gastrointestinal (GI) safety of valdecoxib 20 and 40 mg daily with those of diclofenac 75 mg slow release (SR) twice daily in treating rheumatoid arthritis (RA). METHODS: Seven hundred and twenty-two patients with adult-onset RA were enrolled into this 26-week, randomized, multicentre, double-blind, parallel-group study (246 in the valdecoxib 20 mg daily arm, 237 in the valdecoxib 40 mg daily arm and 239 in the diclofenac 75 mg SR daily arm). Acetylsalicylic acid use (< or =325 mg per day) was similar across all groups: 5.4% in the diclofenac group, 5.7% in the valdecoxib 20 mg group and 5.9% in the valdecoxib 40 mg group. Efficacy was measured by the Patient's Assessment of Arthritis Pain [visual analogue scale (VAS)] and the modified Health Assessment Questionnaire (mHAQ) at baseline and at weeks 2, 6, 8, 12, 18 and 26 of treatment, or at early termination. Upper GI safety was evaluated by endoscopy at the end of treatment, which took place no more than 2 days after the last dose of study medication or at early termination. RESULTS: Valdecoxib 20 and 40 mg daily were comparable to diclofenac 75 mg SR twice daily in treating the signs and symptoms of RA. No significant differences were observed between treatment groups with respect to mean changes from baseline in the Patient's Assessment of Arthritis Pain (VAS) or mHAQ. The incidence of gastroduodenal ulcers in patients receiving valdecoxib 20 mg daily (6%) and valdecoxib 40 mg daily (4%) was significantly lower (P < 0.001) than in patients receiving diclofenac 75 mg SR twice daily (16%). Valdecoxib 20 mg daily was also associated with significantly improved GI tolerability (P = 0.035) compared with diclofenac. CONCLUSIONS: Single daily doses of valdecoxib 20 and 40 mg provided efficacy comparable to that of diclofenac, with a superior upper GI safety profile in the long-term treatment of RA patients.     

Analysis of the reasons for DMARD therapy discontinuation in patients with rheumatoid arthritis in the Czech and Slovak republics

The aim of the study was to evaluate the efficacy and safety of disease-modifying drugs (DMARDs) in everyday clinical practice in Central European States (the Czech and Slovak republics). This was a retrospective, multicentre study. With the help of a special questionnaire, the medical files of 760 patients in 15 centres were analysed looking for reasons for DMARD discontinuation (e.g. insufficient efficacy, toxicity). The secondary endpoints were duration of therapy with individual DMARDs and the influence of other factors (demographic, disease specific, concomitant therapy) on duration of therapy. In 47.1 % of patients therapy was interrupted because of lack of efficacy, in 43.2 % because of adverse events, and in 9 % for undefined reasons. Toxic reactions leading to withdrawal were most common with gold (62.6 %) and methotrexate (62.5 %). Because of insufficient effect, treatment was most frequently interrupted with antimalarials (62.3 %) and penicillamine (53.2 %), but in only 22% treated with methotrexate. The mean duration of one treatment episode with DMARDs was 28.1 t 48.9 months. Surprisingly, it was longest for cyclophosphamide (53.5 + 55.1 months) and shortest for cyclosporin (7.0 t 6.7 months). The mean duration of treatment with methotrexate was only 14.9; t 16.2 months. The mean duration of treatment with one DMARD was statistically longer in patients with positive rheumatoid factor, extra-articular disease and age lower than 50 years. There was no impact of sex, concomitant steroid treatment and high or low sedimentation rate on treatment duration. Considerable differences in everyday clinical practice with DMARDs between Central European states and published data from the US and western Europe have been found. More education about modern strategies in the treatment of RA is probably necessary for practising rheumatologists. Received: 31 January 2001 / Accepted: 22 November 2001     

Efficacy and safety of piascledine 300 versus chondroitin sulfate in a 6 months treatment plus 2 months observation in patients with osteoarthritis of the knee

To investigate that a 6-month treatment with avocado soybean unsaponifiable (Piascledine^® 300 mg) once daily is as effective as with chondroitin sulfate 400 mg three times daily in femorotibial gonarthrosis, and also the carry-over effect for two more months is comparable. Patients were randomized (1:1) to the treatment groups. They received for 6 months 3 capsules chondroitin sulfate per day or one capsule of avocado soybean unsaponifiable (ASU) in a double-dummy technique. A 2-month post-treatment period followed to determine the carry-over effect. Primary efficacy criterion was the change of the WOMAC-index from study begin to end of treatment. Secondary criteria were the changes in Lequesne-index, pain on active movement and at rest, global assessment of efficacy. Three hundred sixty-four patients have been taken up into the trial. Three hundred sixty one patients were eligible for evaluation. One hundred eighty three received ASU 300 mg once daily, one hundred seventy eight chondroitin sulfate three times daily. The WOMAC-index decreased in both groups for approx. 50% to the end of therapy. During the post-treatment observation there was a further slight improvement. There was no statistical significant difference between the treatment groups during the entire observation. All other observed parameters showed the same pattern. The daily intake of rescue medication was reduced continuously. Overall efficacy has been rated excellent and good in more than 80% of the patients in both groups. Both drugs were safe and well tolerated. The first direct comparison between avocado soybean unsaponifiable 300 mg once daily and chondroitin sulfate three times daily reveiled no difference in efficacy or safety aspects between 1 capsule ASU 300 mg per day and 3 capsules chondroitin sulfate per day. It can be assumed that the once daily intake of ASU will lead to a better compliance in routine therapy.     

Characterization of CSOC 882, a novel immortalized ovarian cancer cell line expressing EGFR, HER2, and activated AKT

OBJECTIVE: Only a small number of comprehensively characterized immortalized ovarian cancer cell lines are available for laboratory studies on ovarian cancer. We describe a new ovarian cancer cell line that arose from primary culture of a stage IC, grade III ovarian carcinoma, designated CSOC 882. METHODS: We characterized CSOC 882 by karyotyping, growth modeling, immunohistochemical staining, immunoblotting, drug sensitivity testing, and xenografting in nude mice. RESULTS: CSOC 882 possessed an abnormal tetraploid karyotype including loss of one copy of chromosomes 2, 17, 19, and 21, and deletion of 8p21. Growth of CSOC 882 was best modeled using the logistic growth equation revealing an average doubling time of 31 h. CSOC 882 cells expressed vimentin, cytokeratin, p53, BRCA1, EGF receptor, HER2, androgen receptor, estrogen receptor alpha, and progesterone receptor, while no evidence of estrogen receptor beta or factor VIII was observed. Some but not all CSOC 882 cells were positive for CA125 reflecting the primary tumor, which had patchy CA125 staining. Drug sensitivity assays demonstrated that CSOC 882 was more sensitive to cisplatin and carboplatin than SKOV3 and HCC1937 while CSOC 882 and SKOV3 were both sensitive to paclitaxel unlike HCC1937. CSOC 882 xenografts retained the original characteristics of vimentin, cytokeratin, and factor VIII labeling. CONCLUSIONS: CSOC 882 is an immortalized cell line that has survived more than 130 passages in culture and retained molecular features of the primary tumor from which it was derived. Compared to the most common ovarian carcinoma cell lines, CSOC 882 is a unique resource for genetic and cellular research on ovarian cancer.