Predictive risk factors of serious infections in patients with rheumatoid arthritis treated with abatacept in common practice: results from the Orencia and Rheumatoid Arthritis (ORA) registry.

OBJECTIVES: Little data are available regarding the rate and predicting factors of serious infections in patients with rheumatoid arthritis (RA) treated with abatacept (ABA) in daily practice. We therefore addressed this issue using real-life data from the Orencia and Rheumatoid Arthritis (ORA) registry. METHODS: ORA is an independent 5-year prospective registry promoted by the French Society of Rheumatology that includes patients with RA treated with ABA. At baseline, 3 months, 6 months and every 6 months or at disease relapse, during 5 years, standardised information is prospectively collected by trained clinical nurses. A serious infection was defined as an infection occurring during treatment with ABA or during the 3 months following withdrawal of ABA without any initiation of a new biologic and requiring hospitalisation and/or intravenous antibiotics and/or resulting in death. RESULTS: Baseline characteristics and comorbidities: among the 976 patients included with a follow-up of at least 3 months (total follow-up of 1903 patient-years), 78 serious infections occurred in 69 patients (4.1/100 patient-years). Predicting factors of serious infections: on univariate analysis, an older age, history of previous serious or recurrent infections, diabetes and a lower number of previous anti-tumour necrosis factor were associated with a higher risk of serious infections. On multivariate analysis, only age (HR per 10-year increase 1.44, 95% CI 1.17 to 1.76, p=0.001) and history of previous serious or recurrent infections (HR 1.94, 95% CI 1.18 to 3.20, p=0.009) were significantly associated with a higher risk of serious infections. CONCLUSIONS: In common practice, patients treated with ABA had more comorbidities than in clinical trials and serious infections were slightly more frequently observed. In the ORA registry, predictive risk factors of serious infections include age and history of serious infections.

Positivity for anti-cyclic citrullinated peptide is associated with a better response to abatacept: data from the 'Orencia and Rheumatoid Arthritis' registry.

OBJECTIVES: Very limited data are available regarding the efficacy of abatacept (ABA) in real life. The aims of this study were to determine the efficacy of ABA in rheumatoid arthritis and predicting factors of efficacy in common practice. METHODS: The Orencia and Rheumatoid Arthritis" (ORA) prospective registry, promoted by the French Society of Rheumatology, has included 1003 patients with RA. RESULTS: 773 patients had already fulfilled the 6-month follow-up visit. Only 21.3% of patients would have fulfilled inclusion criteria used in pivotal controlled trials. The European League Against Rheumatism (EULAR) response, was observed in 330 (59.1%) of the 558 assessed patients (good response: 20.4%, moderate response: 38.7%) and was similar in patients who did and in patients who did not fulfill inclusion criteria of controlled trials. Among EULAR responders, initial 28-joint disease activity score (5.4 (4.7-6.5) in responders vs 4.9 (4.0-6.0) in non responders, p< 0.0001), the proportion of rheumatoid factor (75.6% vs 66.7%, p= 0.03) and the proportion of anti-cyclic citrullinated peptide antibody (anti-CCP)-positivity (75.9% vs 62.2%, p= 0.001) were significantly higher. In multivariate analysis adjusted on initial 28-joint disease activity score and CRP, anti-CCP positivity was associated with EULAR response (OR=1.9;95% CI=1.2 to 2.9, p=0.007), but not rheumatoid factor (OR=1.0;95% CI=0.6 to 1.6, p=0.9). Anti-CCP positivity was also significantly associated with a higher ABA retention rate at 6 months. CONCLUSIONS: Real life efficacy of ABA in the ORA registry was similar as that reported in clinical trials. Anti-CCP positivity was associated with a better response to ABA, independently from disease activity.

Spinal curvatures and quality of life in women with vertebral fractures secondary to osteoporosis.

STUDY DESIGN: A prospective cross-sectional case-control study. OBJECTIVES: To compare spinal curvatures in women with osteoporosis and control subjects with a new instrument, the curviscope. SUMMARY OF BACKGROUND DATA: Few instruments are available for measuring spinal curvatures in the sagittal plane. Most of them have poor reproducibility, and they have been poorly investigated in osteoporosis. METHODS: Ninety-eight postmenopausal women were evaluated. They were divided into two groups, according to their bone status: women with osteoporosis with at least one vertebral fracture (n = 51) and control subjects (n = 47). Women with osteoporosis were divided into two subgroups, according to the delay since the last vertebral fracture had occurred (i.e., more or less than 3 months). Quality of life was assessed by using a generic instrument, the Nottingham Health Profile, in patients with osteoporosis only. RESULTS: Reproducibility of the curviscope was satisfactory. For kyphosis measurements, the coefficients of variation were 2.8% and 2.4% in control subjects and women with osteoporosis, respectively. Kyphosis values were significantly higher in women with osteoporosis than in age-matched control subjects (63 degrees +/- 13 degrees vs. 52 degrees +/- 11 degrees, respectively; P < 0.005). Nottingham Health Profile scores were significantly different (P < 0.05) in women with osteoporosis with a recently diagnosed vertebral fracture, compared with other women with osteoporosis in two aspects, physical mobility and energy. Kyphosis measurements were significantly correlated with age in the whole group (r = 0.26; P < 0.05). In the Nottingham Health Profile, physical mobility was significantly correlated with kyphosis (r = 0.35; P < 0.05). CONCLUSIONS: The curviscope is a reliable tool, particularly useful in the assessment of osteoporosis. Moreover, kyphosis angles measured with the curviscope are markedly increased in women with osteoporosis, compared with control subjects. Finally, an increase of kyphosis angles is associated with decreased physical mobility.

[Osteoporotic vertebral crush fractures with severe neurologic manifestations. Apropos of 6 cases]. / Tassements vertébraux ostéoporotiques avec complications neurologiques sévères. A propos de six observations.

Osteoporotic vertebral crush fractures with neurologic complications are rarely reported in the literature. We report six new cases particularly severe in which death occurred in two cases. The study group included four women and two men with a mean age of 75 years (range: 72-79). Vertebral collapse causing neurological deficit was T5, T9, T11 in two cases, L1 and L3. The mean number of vertebral collapses was three per patient (range: 1-9). Back pain appeared without traumatism 6 weeks before admission (range: 1-24). Neurological complications appeared 2.5 weeks after back pain (range: 1-8). One patient suffered from a paraplegia, three from a paraparesia with bladder dysfunction (n = 1). In one case there was a severe weakness of the levator muscles of the foot and in another a L3 femoral neuralgia with severe bowel and bladder dysfunction. X-rays demonstrated backwards displacement of the posterior cortex in three cases, an intravertebral vacuum phenomenon in two cases and a heterogeneous appearance suggesting a malignancy in two cases. Computed tomography, performed in four patients and tomography in one patient, demonstrated fragmentation of the vertebral body in all the cases and vacuum phenomenon in four cases. Magnetic resonance imaging performed in four cases has confirmed the absence of epiduritis and a compression due to bony structures in two cases. A vertebral biopsy was performed in three cases. Osteoporosis was observed in all the cases and in two cases there was also an osteonecrosis. Surgical treatment was performed in three cases and conservative medical treatment in the other cases. After surgical treatment we have observed an absence of improvement of neurological complications in one case, an improvement in another and finally a full recovery in the last case. After conservative treatment we have noted in two cases an absence of improvement of neurological complications and in one case an improvement of neurological deficit. Two patients died (one after medical treatment and another after surgical treatment).

[HLA DRB1 polymorphism in rhizomelic pseudo-polyarthritis and Horton disease]. / Etude du polymorphisme HLA DRB1 au cours de la pseudopolyarthrite rhizomélique et de la maladie de Horton.

Some studies have suggested that distribution of HLA DRB1 alleles in polymyalgia rheumatica (PMR) resembles that found in giant cell arteritis (GCA). However these data are controversial. OBJECTIVE--To evaluate in French native patients whether PMR immunogenetically resembles GCA in determining HLA DRB1 alleles. PATIENTS AND METHODS--Fourty-five patients were included in the study. Twenty-one patients with PMR alone (Bird's criteria) and 24 with GCA (ACR criteria). In 11 patients, GCA was associated with PMR. HLA DRB1 genotype was determined by PCR-RFLP analysis. Statistical analysis was performed by the chi 2 test and determination of the odds ratio (OR). Two hundred and thirty-three unselected normal healthy subjects served as controls. RESULTS--A significant increased prevalence of HLA DR1 was observed in patient with PMR alone and an absence of DR7 (0% vs 10.3%, p = 0.02, OR = 0.1). An increased incidence of DR4 and particularly *0401 allele was only found in patients with GCA (OR = 2.4). No patient with isolated PMR had DR7 genotype compared with 25% in GCA (p < 0.001, OR = 0.03). A comparative study between isolated PMR versus GCA showed a significant increased in DR1 and DR3 alleles in isolated PMR and a significant increased prevalence of DR4 and DRB1 *0701 allele in GCA. CONCLUSION--The present study emphasizes the absence of similarity in HLA DRB1 allele distribution between PMR and GCA. The association of DR7 in patient with GCA seems characteristic in French native patients.

[Cardiac complications in adult onset Still disease: from pericarditis to tamponade as manifestations]. / Complications cardiaques de la maladie de Still de l'adulte: de la péricardite à la tamponade parfois révélatrice.

Pericarditis is a common manifestation of adult still's diseases (ASD), observed in 20% to 3% cases. Pericardial tamponade is more seldom, less than ten cases have been reported in the literature. We reported two observations of patients with ASD and pericardial tamponade above a series of 18 patients with ASD, in one case revealed the disease. The first patient was a 32-year-old women and had fever, arthritis, high white blood cell count and developed pericardial tamponade. The evolution was favourable with bolus of methylprednisolone. In the second case, cardiac tamponade occurred several years after the onset of the disease. Surgical drainage was first required (800 ml) because of inefficacity of oral prednisone. A dramatic improvement was observed after bolus of methylprednisolone. In conclusion pericardial tamponade is a seldom but sometimes the first manifestation of ASD and may required in first intention bolus of methylprednisolone.

[Cardiac complication of adult-onset Still's disease: from pericarditis to tamponade, sometimes a manifestation of the disease]. / Complication cardiaque de la maladie de Still de l'adulte: de la péricardite à la tamponnade parfois révélatrice.

Cardiac tamponade is very seldom complication of adult onset-Still's disease. We reported 2 cases; it was the first manifestation of the disease in one case.

[Rheumatoid polyarthritis in the elderly--rhizomelic pseudopolyarthritis: what differences?]. / Polyarthrite rhumatoïde du sujet âgé--pseudopolyarthrite rhizomélique: quelles différences?

The authors have conducted a comparative retrospective study between polymyalgia rheumatic (N = 26) and rheumatoid arthritis in the elderly (N = 44), including HLA DRB1 genotype determination by PCR-RFLP analysis. No clinical nor biological differences were significant between the 2 groups of patients. However 70% of RA patients had one ore more susceptibility alleles (shared epitope hypothesis) and 50% in polymyalgia rheumatica.

[Initial manifestations and late diagnosis in chronic atrophic polychondritis: apropos of a series of 15 patients]. / Manifestations révélatrices et retard diagnostique dans la polychondrite chronique atrophiante: à propos d'une série de 15 malades.

An auricular or nasal chondritis or a saddle nose deformity are the initial manifestation in half of cases of relapsing polychondritis; the other initial manifestations are various and less evocative; polyarthritis, laryngo-tracheal symptoms, episcleritis which delay the diagnosis. From 15 cases of relapsing polychondritis, the diagnosis time from the first symptom are studied; this one is long, about 3 years and 6 months (from 3 months to 17 years) in 13/15 of the cases even if the first manifestation is typical (external chondritis). In two cases only, the diagnosis was established after the first attack. This late of diagnosis had socioeconomical impact and exposed to severe complications like tracheal chondritis.

[Spondylodiscitis disclosing bacterial endocarditis. Apropos of a case. Review of the literature]. / Spondylodiscite révélatrice d'une endocardite bactérienne. A propos d'une observation. Revue de la littérature.

The authors report a case of infectious spondylodiscitis revealing a staphylococcal endocarditis in a patient with a Carpentier aortic heterograft. This case, along with 60 descriptions from the literature, has enabled them to specify the characteristics of occurrence of endocarditis during a spondylodiscitis. The clinical factors in favor of this association are: a pre-existing cardiopathy, an oral port of entry, occurrence of other rheumatoid manifestations, even more the presence of complications of endocarditis. The laboratory factors in favor of an association are: discovery of an inflammatory anemia, of circulating immune complexes, of a cryoglobulinemia, of a rheumatoid factor, of hematuria. But it is mostly the demonstration of streptococcus in blood cultures and other samples that should be an indication to search for an endocarditis, the course of which dominates the prognosis.

[Effects on the bone metabolism of long-term treatment with antivitamins K1]. / Retentissement sur le métabolisme osseux des traitements au long cours par les antivitamines K1.

Oral anticoagulants (OC) prevent the activation by carboxylation of coagulation proteins. However this action also affects osteocalcin, or bone Gla-protein, a parameter of bone remodelling. Phosphorus and calcium metabolism, osteocalcin levels and bone mineral content were studied in twelve men aged under 60, and who had been taking OC for more than a year, in comparison with a paired group of nine controls with the same cardiovascular pathology but not taking anticoagulants. Osteocalcin levels were lower in the OC group (3.44 ng/ml) than in the control group (5.88 ng/ml) (p = 0.01). There was no significant difference in other phosphorus/calcium balance parameters nor in bone density between the two groups. No evidence was found of any osteopathy in the OC group, but the decrease in serum osteocalcin could result either from inhibition of its secretion or of its carboxylation, or from an action on the osteoblast.

[Unsatisfactory results of intradiscal injection of triamcinolone hexacetonide in the treatment of sciatica caused by intervertebral disk herniation]. / Mauvais résultats de l'injection intradiscale de l'hexacétonide de triamcinolone dans le traitement des sciatiques par hernie discale.

Sciatica caused by intervertebral disc herniation can be treated with intradiscal injection of chymopapain. A search for a cheaper and less allergizing product led to triamcinolone hexacetonide, this procedure being known as "nucleorthesis". The first results at 6 months were encouraging. In 3 centres where triamcinolone hexacetonide was tested with a more than 2 years' follow-up 92 patients could be evaluated. The results obtained were considered satisfactory in 34 patients (36.9 percent), but they were poor in 19 patients (20.6 percent), and 39 patients (42 percent) had to be operated upon within 2 years. Return to surgery took place within the 6 months following nucleorthesis in 18 patients (19.56 percent) and beyond this period in 17 patients (22.8 percent) with degradation of the results. Moreover, calcifications were found in 19 out of 38 patients; they were of varying size, sometimes detected only at computerized tomography, and some of them appeared to produce symptoms. All considered, the failure rates, the number of patients who required surgery and the occurrence of large and sometimes symptomatic calcifications make triamcinolone nucleorthesis unacceptable compared with the recognized percentages of success with papain nucleolysis and surgical operations. For these reasons, we consider that this treatment should be abandoned.

Rituximab therapy for systemic vasculitis associated with rheumatoid arthritis: Results from the AutoImmunity and Rituximab Registry.

OBJECTIVE: Rituximab improves articular symptoms in rheumatoid arthritis (RA) and it recently has been shown to be an effective induction therapy for antineutrophil cytoplasmic antibody-associated vasculitis. We assessed the efficacy and safety of rituximab in a real-life clinical setting among patients with systemic rheumatoid vasculitis (SRV). METHODS: We analyzed data from the AutoImmunity and Rituximab registry, which includes patients with autoimmune diseases treated with rituximab. RESULTS: Of the 1,994 patients with RA enrolled in the registry, 17 were treated with rituximab for active SRV. At baseline, the mean Birmingham Vasculitis Activity Score for RA (BVAS/RA) was 9.6, with a mean prednisone dosage of 19.2 mg/day. After 6 months of rituximab therapy, 12 patients (71%) achieved complete remission of their vasculitis, 4 had a partial response, and 1 died with uncontrolled vasculitis. Mean BVAS/RA was reduced to 0.6 and mean prednisone dosage to 9.7 mg/day. At 12 months, 14 patients (82%) were in sustained complete remission. Severe infection occurred in 3 patients, corresponding to a 6.4 per 100 patient-years rate. In the 6 patients who received further rituximab as maintenance therapy between months 6 and 12, no relapse of vasculitis was observed. However, among the 9 patients who did not, a relapse was observed in 3 patients who were treated with methotrexate alone. Remission was reestablished by reintroducing rituximab in 2 cases. CONCLUSION: Complete remission of SRV was achieved in nearly three-fourths of patients receiving rituximab in daily practice, with a significant decrease in daily prednisone dosage and an acceptable toxicity profile. Rituximab represents a suitable therapeutic option to induce remission in SRV, but maintenance therapy seems to be necessary.