Epidemiological data, efficacy and safety of a paracetamol-tramadol fixed combination in the treatment of moderate-to-severe pain. SALZA: a post-marketing study in general practice.

OBJECTIVE: To evaluate the efficacy and safety of the paracetamol-tramadol combination (PTC) in treating moderate-to-severe pain, in patients aged 65 years and over within general practitioner (GP) practice centers. RESEARCH DESIGN AND METHODS: This was an observational, non-interventional, longitudinal, multicenter, open, non-comparative, prospective study. This intermediary analysis was of patients recruited before the French Health Authority confirmation (25th June, 2009) of the EMEA decision to withdraw all analgesics containing dextropropoxyphen. Trial registration information: This study has been submitted for approval to the CNIL and French Medical Council (CNOM) only. RESULTS: A total of 2663 patients aged 65 years or over were assessed 1 month after inclusion in the study. PTC was prescribed as first-line treatment in 30% of patients and, in the other cases, after failed or inadequate efficacy (69.8%), and/or as a result of safety problems (7.8%) with at least one other analgesic. During the month of the study period 14.7% of patients received an additional rescue analgesic. The study confirmed the efficacy of PTC with regard to pain intensity (-3.1 points reduction of pain scored 6.1 points on inclusion), pain relief (64.8% of patients experienced significant pain relief), patient satisfaction (90.5% of patients satisfied or completely satisfied) and clinical global impression evaluated by the patient (78.7% much or very much improved), regardless of the pain etiologies or duration of the underlying pathology. PTC was well-tolerated in this patient group, who had a mean age of 73.6 ± 6.6 years. A total of 119 patients (4.5%) reported at least one adverse event (AE). All were known and predictable AEs. This percentage is comparable to that found under similar conditions in patients of all ages (4.2%). CONCLUSIONS: PTC, due to the complementary action of its two analgesics, is effective in treating the different types of pain in a GP's practice setting and is well-tolerated, even in an elderly population. Study limitations include all those inherent to non-interventional and open-label observations.

Impact of three anti-TNFalpha biologics on existing and emergent autoimmunity in rheumatoid arthritis and spondylarthropathy patients.

OBJECTIVE: The objective of this study was to analyze the effects of 3 anti-TNFalpha agents on markers of autoimmunity in rheumatoid arthritis (RA) and spondylarthropathy (SPA) patients. METHODS: First-time anti-TNFalpha biologics (infliximab, etanercept, or adalimumab) were prescribed to 156 RA and 95 SPA (58 ankylosing spondylarthritides, 37 psoriatic arthritides). During 1-2 years of follow-up, clinical, biological [antinuclear (ANA) and anti-double-stranded (dsDNA) antibodies, rheumatoid factors (RF), and anti-cyclic citrullinated peptide (CCP) for RA], and therapeutic data were collected biannually. RESULTS: ANA appeared or ANA and anti-dsDNA titers increased significantly (P < 0.001) more under infliximab than etanercept in both rheumatisms and than adalimumab in RA patients. During the 2-year follow-up, ANA appeared more in RA patients taking adalimumab than etanercept (P = 0.003), but independently of the anti-TNFalpha used; anti-dsDNA titers rarely became positive. Under etanercept or infliximab, ANA and anti-dsDNA were not influenced by the underlying pathology nor were they affected by infliximab intensification over 18 months. Only one case of cutaneous lupus was observed in a patient having IgG anti-dsDNA. The therapeutic responses were independent of ANA and anti-dsDNA titers for all rheumatisms and biologics. In RA patients, RF titers, but not anti-CCP levels, declined with the therapeutic response for all biologics. CONCLUSION: This is the first study that has evaluated the impact of three TNFalpha blockers on ANA and anti-dsDNA antibodies in RA and SPA patients. Autoimmunity was more induced with infliximab than etanercept and to a lesser degree to adalimumab but, more importantly, this emergent autoimmunity was exceptionally associated to clinical manifestations of lupus.

Interleukin-1 receptor antagonist (anakinra) treatment in patients with systemic-onset juvenile idiopathic arthritis or adult onset Still disease: preliminary experience in France.

BACKGROUND: Anakinra treatment has been reported to be effective in some patients with systemic-onset juvenile idiopathic arthritis (SoJIA) or adult-onset Still disease (AoSD). OBJECTIVES: To assess the efficacy and the safety of anakinra treatment in SoJIA and AoSD. METHODS: SoJIA and AoSD patients were treated with anakinra (1-2 mg/kg/day in children, 100 mg/day in adults); we analysed its effect on fever, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels, numbers of swollen and tender joints, the assessment of disease activity (by physician and parent/patient) and pain (by parent/patient), and American College of Rheumatology (ACR) pediatric core set criteria for JIA activity. RESULTS: A total of 35 patients were included, 20 with SoJIA and 15 with AoSD. Their mean age (range) at the onset of treatment was 12.4 (3-23) and 38.1 (22-62) years, respectively; disease duration was 7.0 (1-16) and 7.8 (2-27) years, respectively. Active arthritis was present in all cases but one. Of the 20 SoJIA patients, 5 achieved ACR 50% improvement in symptoms (ACR50) response criteria at 6 months. Steroid dose had been decreased by 15% to 78% in 10 cases. A total of 11 of the 15 AoSD patients achieved at least a 50% improvement for all disease markers (mean follow-up: 17.5 (11-27) months). Steroids had been stopped in two cases and the dose was decreased by 45% to 95% in 12 patients. Two patients stopped anakinra due to severe skin reaction, and two patients due to infection: one visceral leishmaniasis and one varicella. CONCLUSION: Anakinra was effective in most AoSD patients, but less than half SoJIA patients achieved a marked and sustained improvement.

Anti-tumour necrosis factor treatment in patients with refractory systemic vasculitis associated with rheumatoid arthritis.

OBJECTIVE: To assess anti-tumour necrosis factor (anti-TNF) agents in patients with refractory systemic rheumatoid vasculitis (SRV). METHODS: 1200 rheumatologists and internists were asked to provide medical files for patients with anti-TNF agents given as a second-line treatment for active SRV refractory to cyclophosphamide and glucocorticoids. RESULTS: We identified nine cases in which anti-TNF drugs were given for active SRV, despite previous treatment with a mean cumulative dose of 8.4 g of cyclophosphamide in association with high-dose glucocorticoids. The mean prednisone dose before anti-TNF therapy was 29.6 mg/day. After 6 months, six patients were in remission (complete in five, partial in one). The treatment failed in one patient and two patients stopped taking the anti-TNF treatment due to side-effects. Mean prednisone dose was reduced to 11.2 mg/day. Severe infection occurred in three patients. Relapses were observed in two patients. Remission was re-established by reintroducing anti-TNF therapy in one case and increasing the dose in the other. CONCLUSIONS: This study provides evidence of efficacy of anti-TNF therapy in adjunct to glucocorticoids for treating active refractory SRV. Remission was achieved in two-thirds of patients, with a significant decrease in prednisone dose, although there was a high rate of infection in these severely ill patients.

Autoantibodies, metalloproteinases and bone markers in rheumatoid arthritis patients are unable to predict their responses to infliximab.

OBJECTIVES: To identify biochemical, immunological and bone markers as predictors of rheumatoid arthritis (RA) patients' responses to infliximab. METHODS: A total of 76 patients with active RA (American College of Rheumatology criteria), refractory to disease-modifying anti-rheumatic drugs, including methotrexate, received infliximab (3 mg/kg) infusions at weeks 0, 2, 6, and then every 8 weeks in combination with methotrexate or leflunomide. At week 14, infliximab efficacy was evaluated using disease activity score (DAS)28. A serum sample, collected just before starting infliximab, was tested by ELISA (unless stated otherwise) for the following immunological markers: rheumatoid factor by agglutination and ELISA (IgA, IgG and IgM isotypes); anti-cyclic citrullinated protein; autoantibodies recognizing calpastatin domain I and its 27 C-terminal fragment, glucose-6-phosphate isomerase, alpha-enolase; anti-keratin and anti-perinuclear factor antibodies (immunofluorescence); biochemical markers: C-reactive protein (nephelometry), metalloproteinase-1 and -3, tissue inhibitors of metalloproteinases-1 and -2, antioxidants (vitamins A and E; selenium); bone resorption markers: pyridinoline, deoxypyridinoline, osteoprotegerin, soluble receptor activator of nuclear factor-kappaB ligand, cartilage oligomeric matrix protein. Each parameter's predictive value of the response to infliximab was analysed using Fisher's exact, Mann-Whitney and chi-square tests. Hierarchical clustering was performed with The Institute for Genomic Research (TIGR) multiple experiment viewer software. RESULTS: Good, moderate and non-responder rates were 6.5, 61.8 and 31.5%, respectively. No significant difference was observed between responders and non-responders, regardless of the serum parameters considered. Analysis of dichotomous or continuous variables failed to identify markers predictive of a good or poor response to infliximab. CONCLUSION: The search for soluble markers in RA patients' sera likely to predict response to infliximab because of their involvement in RA pathogenesis seems disappointing. However, because of the limited power to detect smaller differences in biomarkers, the present study is a preliminary exploratory analysis.

[Cutaneous vasculitis with necrotic ulcers in rheumatoid arthritis: treatment with anti-TNFalpha]. / Vasculite avec ulcérations cutanées au cours de la polyarthrite rhumatoïde: traitement par anti TNFalpha.

INTRODUCTION: Anti-TNFalpha has occasionally been used in the treatment of recalcitrant forms of systemic vasculitis such as Behçet's disease, Wegener's granulomatosis and Churg-Strauss syndrome. We report on the outcome of treatment in rheumatoid arthritis patients with cutaneous vasculitis lesions on anti-TNFalpha. OBSERVATIONS: Two patients with rheumatoid arthritis present for several years had necrotic ulcers of the lower limbs due to cutaneous vasculitis. After the failure of various immunosuppressive drugs (cyclophosphamide, azathioprine, methotrexate), the two patients were treated with anti-TNFalpha: infliximab in the first case and adalimumab in the second. Cutaneous ulcers healed within two to four months of the start of anti-TNFalpha treatment. Despite ongoing anti-TNFalpha treatment, these cutaneous ulcers relapsed four to six months after complete healing. CONCLUSION: Initially spectacular healing of cutaneous vasculitis ulcers under anti-TNF alpha treatment followed by relapse after several months of treatment is suggestive of an escape mechanism.

Diagnostic and prognostic values of anti glucose-6-phosphate isomerase antibodies in community-recruited patients with very early arthritis.

The objective of this study was to determine the diagnostic and prognostic values of antiglucose-6-phosphate isomerase (GPI) antibodies in patients with very early arthritis. Anti-GPI antibodies were measured by ELISA using purified GPI from rabbit muscle in: (i) 383 sera from healthy blood donors (n = 120), well-established rheumatoid arthritis (RA) (n = 99) and non-RA differentiated arthritis (NRADA) (n = 164) patients; (ii) 195 sera obtained from community-recruited patients with very early inflammatory arthritis (VErA cohort) that were studied for 1 year and classified as having RA (n = 116), NRADA (n = 41), and undifferentiated arthritis (UA) (n = 38) after the follow-up period. The criterion for severity was the progression of radiographic damage. Prevalence of anti-GPI antibodies was significantly higher in well-established RA patients (45.4%) compared to healthy subjects (2.5%). Anti-GPI antibodies were also present in sera from NRADA: systemic lupus erythematosus 53%, polymyositis 45.4%, adult-onset Still's disease 44%, systemic sclerosis 42.8%, spondylarthropathies 25% and primary Sjögren's syndrome 5.8%. No significant association was found between the presence of anti-GPI antibodies and the 3 diagnostic groups from the VErA cohort. No correlation was observed between anti-GPI and autoantibodies usually associated with RA. Anti-GPI antibodies were not predictive of radiological progression in patients with very early arthritis. Thus, anti-GPI antibodies are not useful for discriminating RA from non-RA rheumatic diseases and do not constitute a predictive factor of structural damage.

A shock associated with adult-onset Still's disease.

Only two cases of adult-onset Still's disease associated with shock have been previously described. We report a case of shock in a man with adult-onset Still's disease and discuss the relationship between the two processes by assessing tumor necrosis factor-alpha, procalcitonin and interleukin-6 concentrations.

Efficacy of etodolac on gait in hip osteoarthritis as assessed by Bessou's locometer: a randomized, crossover, double-blind study versus placebo. Groupe de Recherche sur le Handicap de L'appareil Locomoteur.

OBJECTIVES: To assess the efficacy of a single, oral dose of etodolac (300 mg), a nonsteroidal antiinflammatory drug, on gait and pain in patients with unilateral hip osteoarthritis (hOA). DESIGN: Sixteen patients (8 F, 8 M; mean age: 61+/-11.2 years) with painful hOA were included in a randomized, crossover, double-blind study versus placebo. Space and time parameters were assessed using Bessou's locometer and pain was evaluated using the visual analog scale (VAS) at t0 (before taking the drug), t60 (min), t120, and t180 after taking a 300-mg tablet of etodolac. RESULTS: Walking speed was significantly faster only between t0 and t180 under etodolac versus placebo (P< 0.02). Walking speed increased between t0, t60, t120 and t180 with etodolac (P< 0.003), but not with placebo. Stride length increased (P< 0.0001) only on the hOA side, while the time parameters of gait for etodolac- and placebo-treated patients did not differ. VAS values differed significantly at t0 (P< 0.01) between etodolac and placebo groups, but no significant difference was observed at t60, t120 and t180. CONCLUSIONS: Bessou's locometer was able to demonstrate the efficacy of 300 mg of etodolac on gait in hOA. Walking speed was faster 3 h after taking the drug, essentially due to a greater stride length. Pain reduction in the etodolac group contributed to gait improvement. It was concluded that gait performances improved because of less hip pain and thus a greater range of motion after etodolac intake.

Evolution of chronic recurrent multifocal osteitis toward spondylarthropathy over the long term.

OBJECTIVE: To retrospectively assess, with a sufficiently long followup (mean 11.6 years; median 9 years), the long-term outcome of chronic recurrent multifocal osteitis (CRMO), a multifocal, inflammatory bone disease. METHODS: Patients included were 8 children/adolescents and 7 adults with no family history of rheumatic disease who had been diagnosed as having CRMO between 1979 and 1995. Ten patients had undergone at least 1 bone biopsy of the lesions, with histologic examination and multiple cultures. In 1996, in addition to an in-depth interview, 12 patients underwent an extensive physical examination, laboratory evaluation, HLA-A, B, C, and DR typing, bone radiography and scintigraphy, and computed tomography scan of the sternoclavicular and sacroiliac joints. RESULTS: Remission was observed in 3 patients. The other 12 patients developed various associations of vertebral (n = 10), sacroiliac (n = 6), anterior thoracic (n = 7), peripheral articular (n = 2), enthesopathic (n = 4), or dermatologic (palmoplantar pustulosis in 3 cases and psoriasis in 2) involvements. Spine involvement was the most common and occurred the earliest (median time to appearance after the onset of osteitis 5.63 years). Clinical sacroiliitis was always unilateral. No patients carried the HLA-B27 haplotype. CRMO responded well to nonsteroidal antiinflammatory drugs. Twelve patients met the European Spondylarthropathy Study Group criteria for spondylarthopathy. CONCLUSION: After 10 years, CRMO had usually evolved to spondylarthropathy, but with certain features not usually seen in the latter: predominantly, unilateral sacroiliitis, no familial form, and no link with HLA-B27.

Therapeutic trials in hand osteoarthritis: a critical review.

OBJECTIVE: To perform a critical review of the published therapeutic trials conducted in hand osteoarthritis (OA). METHOD: A Medline research was performed to select the clinical trials in hand OA published since 1994. RESULTS: Twenty-five published studies were identified by this research, of which 10 were reported in abstract or short report forms. The trials were classified according to the study drug, and their methods and results examined. The critical analysis focuses on the design, the inclusion and efficacy criteria and the methodological limitations in all of these studies. CONCLUSION: Methodological restrictions of the studies are elucidated, such as the need for a consensus on diagnosis of hand OA, the need of valid, reliable and sensitive to change clinical assessment tools and validated radiological assessment methods in order to conduct trials in the future.

Methodology for the assessment of treatments in hand osteoarthritis.

OBJECTIVE: To perform a review of methods in clinical trials of hand OA and outline a set of guidelines. METHODS: Methods related to assessing treatment in hand OA were classified as those obtaining general consensus and those on which there was disagreement and need for further work. RESULTS: It was agreed that criteria validated for trials in knee and hip OA must be re-evaluated for hand OA; and that populations studied, trial parameters and evaluation tools should meet criteria established herein. Consensus was not reached or further work is required regarding functional index, daily or weekly questionnaire, hand(s) taken into account, scoring system and consideration of aesthetic damage. CONCLUSION: New therapeutic trials are needed in hand OA. Guidelines for future trials are given. International

[Treatment of arthroses in the elderly patient]. / Les traitements de l'arthrose du sujet âgé.

BACKGROUND: Elderly subjects with osteoarthritis are treated with analgesic drugs, non-steroidal antiinflammatory drugs (NSAID) and intra-articular corticosteroid injections as well as symptomatic slow acting drugs in osteoarthritis (Sy-SADOA). BASIC REGIMENS: Initial treatment for osteoarthritis pain should be paracetamol, followed by NSAID if necessary, especially in the elderly, because of their adverse effects. EFFICACY: Sy-SADOA are effective on pain and function with a persistent effect, allowing the reduction of analgesic and NSAID dosage.

Spinal abscess and spondylitis due to actinomycosis.

STUDY DESIGN: Report of a rare case of spinal actinomycosis in a young immunocompetent woman. OBJECTIVE: To show the difficulties in diagnosing spinal actinomycosis. SUMMARY OF BACKGROUND DATA: Spinal actinomycosis is rare and usually occurs as a result of a contiguous (abdominal, pelvic, or thoracic) spread of the infection. This localization represents less than 5% of the infectious sites and was mainly, before the penicillin era, a postmortem discovery. METHODS: A case is reported of a 34-year-old Algerian woman who had fever, persistent cough, right-side thoracic pain, and progressive severe back pain. Radiographs, computed tomographic scan, and magnetic resonance imaging demonstrated lytic areas on the vertebral bodies of T11 and T12 and a paravertebral mass, without disk involvement. A surgical biopsy of T12 and the paravertebral abscess was performed. RESULTS: Presence of characteristic sulfur granules and gram-positive filamentous bacteria in surgical biopsy tissues and isolation of Actinobacillus actinomycetemcomitans in cultures led to the diagnosis of vertebral actinomycosis. The patient was virtually free of pain and fever after a 3-month regimen of ofloxacin and rifampicin (Rifadine, Marion-Merell, France) and was without recurrence after 18 months of follow-up. CONCLUSIONS: Actinomycosis of the spine, caused by the spread of a paraspinal abscess, is extremely rare. The previously poor prognosis has been transformed by antibiotics.

Computed tomography of sternoclavicular joint lesions in spondylarthropathies.

UNLABELLED: To evaluate the computed tomography (CT) findings of inflammatory lesions of the sternoclavicular joints (SCJ) in spondylarthropathies. DESIGN AND PATIENTS: CT scans of the SCJs were obtained in 23 patients (group 1) with inflammatory SCJ lesions in spondylarthropathies. These scans were reviewed by four readers and compared with the CT scans of 23 matched controls (group 2). Each reader had to complete a 27-item grid. RESULTS AND CONCLUSION: In the 23 patients of group 1, the mean number of observed signs was 5.3 +/- 4.2 higher (P < 0.01) than in the group of 23 matched controls (2.4 +/- 1.6). Four signs were more frequently observed (P < 0.05) in group 1: surrounded subchondral clavicular erosions and cysts, surrounded subchondral sternal cysts and sternal bone sclerosis. A cyst and/or an erosion was associated with hyperostosis and/or bone sclerosis in 9 of 23 patients in group 1. This association was not observed in group 2; the difference was significant (P < 0.001). A cyst and/or an erosive lesion was observed 18 times in group 1 versus 11 times in group 2; the difference was significant (P < 0.05). Conversely, signs of degenerative lesions (osteophytes, subchondral sclerosis, unevenness of joint surface) were no more frequently observed in controls than in group 1. This study emphasizes the diagnostic value of CT, in particular in the identification of inflammatory lesions, even when pre-existing degenerative disease is present.

Leiomyosarcoma of the tibia. Report of a case.

A 48-year-old man with an unremarkable medical history was admitted for a painful swelling over the anteromedial aspect of his right leg. Radiographs disclosed heterogeneity of the proximal tibia, with increased uptake on the bone scan. Computed tomography findings consisted of heterogeneity of the proximal tibial metaphysis and diaphysis with subtle cortical osteolysis, periosteal appositions and soft tissue involvement. Magnetic resonance images showed low signal from the metaphysis, diaphysis and soft tissues on T1 sections that enhanced after gadolinium and converted to high signal on T2 images. Lung metastases were also found. Histologic features were consistent with leiomyosarcoma, which was considered to have originated in the tibia since no other primary localization was found. Combination chemotherapy was successful in eliminating the clinical manifestations and clearing the lung metastases. Six months later, the same chemotherapy regimen failed to improve a local and pulmonary recurrence and the patient died a few months later. Primary leiomyosarcoma of bone is a rare tumor, of which one of the most characteristic locations is the proximal third of the tibia. Magnetic resonance imaging with both T1- and T2-weighted sequences is essential to evaluate intramedullary and soft tissue tumor spread. To our knowledge, there are no characteristic signal patterns allowing to differentiate leiomyosarcoma from other primary malignancies of bone. Immunohistochemical and electron microscope studies are useful diagnostic tools.

Peripheral neurological involvement as the first manifestation of spina bifida occulta.

A 42-year-old male was admitted for right-sided sciatica with asymptomatic septic arthritis of the fifth toe of the right foot. He had a history of active chronic hepatitis C and septic arthritis of the fifth toe of the left foot. His symptoms included low back pain, poorly systematized right-sided sciatica, impairment of all forms of sensation in both lower limbs, absent ankle jerks, episodes of urinary retention, urgency, and painless septic arthritis of the fifth toe of the right foot. Roentgenograms showed a spina bifida occulta of L5 and a bony erosin in the distal interphalangeal joint of the right fifth toe. Distal denervation in the territory of L5 was demonstrated by the electromyographic study. Magnetic resonance imaging disclosed an area of high signal on T1 and T2 images, located within the spinal canal opposite L4 and suggestive of an intraspinal lipoma, as well as tethering of the spinal cord in an abnormally distal position. Antimicrobial therapy was effective in ensuring resolution of the infectious arthritis. The low back pain and sciatica responded to nonsteroidal antiinflammatory drug therapy and did not recur subsequently. Many patients who have roentgenograms taken to evaluate low back pain and sciatica are found to have a spina bifida occulta. This complex birth defect involving the spinal canal, meninges and spinal cord or cauda equina can cause neurologic and/or urinary symptoms in adulthood. Magnetic resonance imaging is essential in this situation to evaluate the spinal cord and to look for an intraspinal lipoma.