Efficacy of infliximab in refractory ankylosing spondylitis: results of a six-month open-label study.

OBJECTIVE: To evaluate the efficacy and safety of a loading regimen of the anti-tumour necrosis factor alpha (TNF-alpha) antibody infliximab in predominantly axial severe ankylosing spondylitis (AS). METHODS: We enrolled in this study 50 patients (76% males, 87% HLA-B27(+), median age 35 yr, median disease duration 13 yr) with active AS [Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) >or=30/100 and serum C-reactive protein concentration >or=15 mg/l) despite treatment with a non-steroidal anti-inflammatory drug, and without peripheral arthritis, uveitis or active inflammatory bowel disease. Other disease-modifying anti-rheumatic drugs were discontinued >or=3 months before inclusion and were not allowed during the study. Patients received three infusions of infliximab (5 mg/kg) at weeks 0, 2 and 6 and were monitored clinically and biologically until week 24. RESULTS: Forty-eight patients completed the treatment. In intention-to-treat analysis, all parameters were significantly improved at week 2 and generally reached maximal improvement at week 8. The proportion of responders, defined by a reduction of >or=20% in the global assessment of pain (GAP) or by the AS Assessment Study Group (ASAS 20%) criteria, and the proportion of patients reaching partial remission were 98, 94 and 70% respectively. Relapse, defined as >or=50% loss of maximal GAP improvement, occurred in 73% of completers, with a median delay of 14 weeks after the third infusion. No serious adverse event related to the treatment was observed. CONCLUSIONS: This study confirms, in a large group of severely affected AS patients, the remarkable efficacy of infliximab. Relapse usually occurred after discontinuation of the drug, but almost one-third of completers were still free of relapse 4 months after the last infusion.

Comparison of the responsiveness of symptomatic outcome measures in knee osteoarthritis.

OBJECTIVE: A number of international scientific societies have recommended a core set of domains to be systematically assessed in clinical research studies on osteoarthritis (OA), i.e., pain, function, and patient's overall assessment. This open, longitudinal, observational study compares the responsiveness of different symptomatic variables evaluating these 3 domains in knee OA. METHODS: Patients were individuals with painful knee OA. The collected data were Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale (0-100) and WOMAC function subscale (0-100), Lequesne's index (0-100), pain after physical activities (visual analog scale [VAS] 100 mm), and patient's global assessment (VAS 100 mm). The procedure used was knee joint lovage. Time of collection was before and 1, 3, and 6 months after the lavage. Analysis was by comparison of the standardized response mean (mean of the changes/SD of the changes) in an intent-to-treat strategy after 1, 3, and 6 months using the jackknife method. RESULTS: Improvement in all dimensions of WOMAC subscale scores and VAS scores was observed at month 1. Lequesne's index was not responsive to change. The standardized response mean was moderate, ranging from 0.00 to 0.40. Comparison of the estimates of the standardized response means using the jackknife method showed a statistically significant difference between Lequesne's index and the WOMAC subscale for function, but not between VAS pain and the WOMAC subscale for pain. CONCLUSION: Most of the evaluated variables have a moderate responsiveness. In knee OA, the WOMAC function scale seems to be more sensitive than Lequesne's index for detecting changes after symptomatic therapy.

Intensified-dose (4 gm/m2) cyclophosphamide and granulocyte colony-stimulating factor administration for hematopoietic stem cell mobilization in refractory rheumatoid arthritis.

OBJECTIVE: To evaluate the feasibility, safety, and efficacy of intensified-dose cyclophosphamide (ID-CYC), followed by granulocyte colony-stimulating factor (G-CSF) administration for collection of peripheral blood hematopoietic stem cells (HSC), for patients with severe, refractory rheumatoid arthritis (RA). METHODS: Four patients with severe refractory RA were enrolled in this open study. They received a single infusion of CYC (4 gm/m2) at day 0 followed by G-CSF (5 microg/kg/day) from day 6 until the last day of leukapheresis (performed at the time of hematopoietic recovery) to harvest peripheral blood HSC. Patients were monitored for disease activity, adverse effects, and hematopoietic reconstitution following this procedure. RESULTS: For all patients, administration of ID-CYC induced an early, dramatic improvement of disease activity. Long-term followup indicates that partial disease relapse was observed for all patients. No adverse effect was directly attributable to the treatment procedure. For most patients, HSC collection was sufficient to provide a graft enriched in CD34+ cells by positive selection as well as an unselected rescue graft. CONCLUSION: Patients with severe, refractory RA can benefit from ID-CYC. This procedure, followed by G-CSF administration, appears safe and technically suitable. In addition, it allows immediate improvement of RA activity that can occasionally persist beyond 6 months.

[Subacute or initially chronic osteomyelitis in children. A series of 17 cases]. / L'ostéomyélite subaiguë ou chronique d'emblée chez l'enfant. Une série de 17 cas.

17 cases of subacute or at once chronic osteomyelitis are shown. At this occasion, an analysis of epidemiological, topographical, clinical and bacteriological data is given. An immunological study has been made in 5 cases: diagnosis is difficult at all stages. A reflexion is proposed concerning the treatment to be performed.