[Effectiveness, therapeutic maintenance and reasons for stopping tocilizumab (TCZ): A retrospective and monocentric study in 88 patients followed for rheumatoid arthritis (RA) at the Reims university hospital]. / Efficacité, maintien thérapeutique et motifs d'arrêt du tocilizumab (TCZ) : étude monocentrique et rétrospective chez 88 patients suivis pour une polyarthrite rhumatoïde (PR) au CHU de Reims.

OBJECTIVE: Study the therapeutic maintenance, efficacy and reasons for tocilizumab stop in daily practice. PATIENTS AND METHODS: A monocentric, retrospective study of patients treated for rheumatoid arthritis who received at least one TCZ infusion between January 2009 and December 2015. Therapeutic maintenance was evaluated using the Kaplan-Meier method. The efficacy of TCZ was measured by DAS28 and the EULAR response. Reasons for stopping and new treatment lines were also collected. RESULTS: Of the 88 patients (83% women and 17% men) who were included, the mean age was 54±12.5 years. There were 75% positive rheumatoid factors and 76% positive anti-CCP. The mean duration of the follow-up was 31 months. TCZ was used as monotherapy in 24 patients (27%). Before the introduction of TCZ, the mean DAS28 was 5.07±1.32. The EULAR response at 1 year in patients still under treatment (n=63) was obtained in 59 (93.7%) patients, 46 good responders and 13 moderate responders. Therapeutic maintenance was 82.9%, 72.5%, 68.7% and 57.2%, respectively, at 12, 24, 36 and 54 months. Twenty-eight patients (32%) followed TCZ, 10 for adverse events and 14 for ineffectiveness. Abatacept was the main new therapeutic line. CONCLUSION: The therapeutic maintenance of TCZ in common practice over a long period of follow-up is similar to pivotal studies. Efficacy data are reassuring in the long-term.

[Efficacy and safety of ustekinumab in psoriatic arthritis after anti-TNFα failure in routine practice]. / Ustekinumab dans le rhumatisme psoriasique après échec des anti-TNFα en pratique courante.

PURPOSE: Evaluation of effectiveness and safety of ustekinumab in psoriatic arthritis after anti-TNFα failure. METHODS: We conducted a retrospective and monocentric study. The evaluation of articular and cutaneous effectiveness by the patient was made with numeric scale and satisfaction scale and by the physician during a rhumatological-dermatological consultation. The safety was analyzed by collecting the adverse effects. RESULTS: Nine patients with anti-TNF failure were included. Five of them stopped the treatment because of severe adverse effects. The mean duration treatment of ustekinumab was 24 months. Articular and cutaneous effectiveness were respectively 4.4/10 and 6.7/10. Two thirds of the patients were "satisfied" and one third could stop any analgesic treatment. The mean PASI score decreased from 8.4 to 1.7 after 3 months treatment. Only minor adverse effects were collected and there were no recidivism of the adverse effects observed with anti-TNFα. CONCLUSION: Ustekinumab is an effective and safe alternative for patients with anti-TNFα failure in psoriatic arthritis.

Sarcoid-like granulomatosis in patients treated with tumor necrosis factor blockers: 10 cases.

OBJECTIVE: TNF blockers have been recently evaluated for treating refractory sarcoidosis and could be efficient. However, several cases of sarcoidosis have been diagnosed during anti-TNF therapy. Here, we report the largest series of sarcoid-like granulomatosis following TNF blocker treatment. METHODS: A call for observations of sarcoid-like granulomatosis following TNF blocker treatment was sent to the members of the French 'Club Rhumatismes et Inflammation'. Histological evidence of granulomatosis was required. RESULTS: Observations of 10 patients [seven females; median age 50.5 (range 27-72) years] with sarcoid-like granulomatosis while on anti-TNF treatment were collected: five were treated with etanercept and five with monoclonal antibodies; four patients received TNF blockers for RA and six for SpA. The median delay between anti-TNF agent introduction and granulomatosis diagnosis was 18 (range 1-51) months. Clinical symptoms were mainly pulmonary and cutaneous. Angiotensin-converting enzyme activity was increased in six cases. Lymph-node and/or lung involvement were observed by CT scan of the chest for eight patients. The median delay between drug discontinuation and remission was 6 (range 1-11) months for clinical signs and 6 (range 2-12) months for biological and radiographic findings. Improvement was observed in all patients after drug discontinuation with or without steroids. CONCLUSIONS: Sarcoid-like granulomatosis is rare but not exceptional in patients treated with TNF blockers (approximately 1/2800) and does not seem to be related to gender, rheumatic disease or in our series the type of anti-TNF drug used (monoclonal antibodies or soluble receptor). Discontinuation of anti-TNF usually leads to recovery.

Impact of Bariatric Surgery on Bone Mineral Density: Observational Study of 110 Patients Followed up in a Specialized Center for the Treatment of Obesity in France.

INTRODUCTION: Bariatric surgery is used to treat severe obesity. We aimed to investigate the incidence of clinically significant bone mineral density (BMD) loss at 6 and 12 months after bariatric surgery. METHODS: Observational study performed in a specialized center for the treatment of obesity at the University Hospital of Reims, France. Surface BMD was measured by dual x-ray absorptiometry (DEXA). A reduction of > 0.03 g/cm2 was considered clinically significant. RESULTS: A total of 110 patients were included. A clinically significant reduction in BMD was observed in 62.1% of patients at 6 months, and in 71.6% at 12 months after surgery. No case of osteoporosis was observed. There were four cases of osteopenia and one fracture post-surgery. BMD loss was related by univariate analysis to the reduction in body mass index (BMI) (p < 0.01), weight loss (p < 0.01), fat mass (p < 0.01), and lean mass (p < 0.01). Multivariable analysis found a significant association between the reduction in BMD and the excess weight loss percentage (odds ratio 1.11, 95% confidence interval (1.05-1.18), p < 0.001). CONCLUSION: There was a clinically significant reduction in BMD at 6 months after surgery in over 60% of patients undergoing bariatric surgery. BMD loss is persistent over time and predominantly situated at the femoral level, and strongly associated with weight loss. Systematic vitamin and calcium supplementation, as well as follow-up by DEXA scan seems appropriate. Systematic DEXA scan pre- and post-surgery, and annually thereafter until weight has stabilized seems appropriate.

Tocilizumab Effectiveness After Switching from Intravenous to Subcutaneous Route in Patients with Rheumatoid Arthritis: The RoSwitch Study.

INTRODUCTION: The main objective of this work was to assess the maintenance of effectiveness of subcutaneous tocilizumab 6 months after switching from intravenous to subcutaneous formulation in patients with rheumatoid arthritis (RA) in a real-world setting. Secondary objectives aimed to describe the characteristics of patients and disease, the effectiveness at 12 months after switching, the therapeutic maintenance, and to search for predictive factors of switching. METHODS: We analyzed all the RA patients of the shared medical file "RIC Nord de France", treated with tocilizumab, switching or not from intravenous to subcutaneous tocilizumab, between April 2015 and January 2016. The primary effectiveness endpoint was the proportion of patients remaining in their DAS28-ESR category remission/low disease activity (LDA) or moving to an inferior DAS28-ESR category at 6 months. Since RoSwitch was an observational study, without randomization, a propensity score was built in a sensitivity analysis to balance on RA and patients' characteristics at inclusion between switching and no-switching groups. RESULTS: An improvement of initial DAS28-ESR category or maintenance in DAS28-ESR remission/LDA at 6 months was shown in 203 of the 285 patients with an evaluation for the primary criterion (71.2%, 95% CI [65.6-76.4%]) without differences between groups (73.3%, 95% CI [63.0-82.1%] vs. 70.3%, 95% CI [63.3-76.6%]). The RoSwitch study showed the maintenance of effectiveness at 6 and 12 months. Similar therapeutic maintenance rates were observed for switch and no-switch patients. No clinical factor was associated with the switch in patients in remission/LDA at inclusion. CONCLUSIONS: The RoSwitch study showed the maintenance of effectiveness at 6 months in RA patients switching from intravenous (IV) to subcutaneous (SC) tocilizumab. FUNDING: Roche SAS and Chugai Pharma France.

Association between hidradenitis suppurativa and spondyloarthritis.

OBJECTIVES: We aimed to investigate the existence of an association between hidrosadenitis suppurativa and spondyloarthritis. METHODS: We performed a single-centre, cross-sectional study in patients with hidrosadenitis suppurativa followed in a tertiary care center, and in healthy volunteers without dermatological disease, matched for age (±5years) and gender. For each subject included, clinical examinations, HLA-B27 testing and sacro-iliac MRI were performed in order to diagnose spondyloarthritis according to the Assessment of SpondyloArthritis international Society (ASAS) criteria. RESULTS: In total, 39 subjects were included in each group (70% women in each group, mean age 35.6±11.1 in the hidrosadenitis suppurativa group and 36.0±11.1 in the control group). Eleven (28.2%) patients in the hidrosadenitis suppurativa group were diagnosed with spondyloarthritis (in 4 of these, spondyloarthritis was already previously documented), and in 1 (2.6%) subject in the control group (OR 11.0; 95% CI 4.1-83.3; P=0.02). Axial spondyloarthritis was the most common form of spondyloarthritis, observed in 9/11 patients in the hidrosadenitis suppurativa group, the remainder were peripheral spondyloarthritis. In the hidrosadenitis suppurativa group, only HLA B27 was found to be associated with a diagnosis of spondyloarthritis. CONCLUSIONS: Our results indicate that hidrosadenitis suppurativa is significantly associated with an increased risk of spondyloarthritis, independently of age and sex. Patients with hidrosadenitis suppurativa presenting osteoarticular symptoms, specially low back pain or dactylitis, should be monitored for spondyloarthritis.

Cost Effectiveness of Intra-Articular Hyaluronic Acid and Disease-Modifying Drugs in Knee Osteoarthritis.

BACKGROUND: The place of disease-modifying osteoarthritis drugs (DMOADs) and intra-articular hyaluronic acid (IAHA) in the therapeutic arsenal for knee osteoarthritis (OA) remains uncertain. Indeed, these treatments have demonstrated symptomatic efficacy but no efficacy for disease modification. OBJECTIVE: This report reviews the cost effectiveness of IAHA and DMOADs used in the treatment of knee OA. METHODS: A systematic literature search of the MEDLINE, Scopus, EMBASE and Cochrane databases was performed independently by two rheumatologists who used the same predefined eligibility criteria to identify relevant articles. Papers without abstracts and in languages other than English or French were excluded. Extracted costs were annualised and converted to 2015 euros (€) using the Consumer Price Index of the relevant countries and the 2013 Purchasing Power Parities between these countries and the European Union average. RESULTS: A total of 95 abstracts were selected, and 13 articles were considered for the review: nine articles on IAHA and four on DMOADs. Only one article directly compared different IAHA compounds. Articles showed substantial heterogeneity in methodological approaches. The incremental cost-effectiveness ratios (ICERs) ranged from €4000 to €57,550 and from €240 to €53,225 per quality-adjusted life-year (QALY) gained for DMOADs and IAHA, respectively. CONCLUSIONS: This review highlights substantial heterogeneity between studies, ranging from a cost saving (or dominating) position to very high ICERs, far above the acceptability threshold of €50,000/QALY. Additional research is needed to determine reliable and robust ICER estimates for knee OA therapies.

Incidence of paradoxical reactions in patients treated with tocilizumab for rheumatoid arthritis: Data from the French registry REGATE.

OBJECTIVES: Assess the frequency of paradoxical reactions encountered in daily practice under tocilizumab, using the REGATE (Registry-RoActemra) registry. The secondary objectives were to determine the type of paradoxical reaction and the consequences of these reactions. METHODS: The REGATE registry is an independent prospective registry, promoted by the French Society of Rheumatology, consisting of patients treated with tocilizumab for rheumatoid arthritis. The paradoxical reaction was retained if it was a paradoxical precipitation of a condition for which tocilizumab was indicated, if tocilizumab was being used for an alternative indication, and if it appeared after at least one tocilizumab infusion. RESULTS: Among the 1491 patients included with at least one follow-up visit (3429 patient-years), a paradoxical reaction occurred in 9 patients (0.60% of patients; 2.62/1000 patient-years). These were 7 de novo pathologies (3 vasculitis, 3 uveitis, 1 lupus) and 2 exacerbations of pre-existing conditions (1 vasculitis, 1 lupus). Permanent discontinuation of tocilizumab was chosen for 5 patients. CONCLUSIONS: In the REGATE registry, the occurrence of paradoxical reactions in patients treated with tocilizumab was rare.

Chronic monoarthritis and previous history of cancer: think about synovial metastasis.

Synovial metastases are rare events. Only 37 cases diagnosed by synovial fluid cytologic examination and/or by microscopic investigation of synovial biopsies have been previously reported in the literature. We report another case of shoulder chronic arthritis due to a recurrence of rectal adenocarcinoma and review previous published observations. Generally, this condition carries a poor prognosis with average patients survival of less than 5 months. The possibility of metastatic disease should be considered when an elderly person or patient with a history of previous malignancy presents with a chronic arthritis.

[Efficacy of percutaneous laser disc decompression for radiculalgia due to lumbar disc hernia (149 patients)]. / Efficacité de la nucléolyse laser dans le traitement des radiculalgies par hernie discale (149 patients).

OBJECTIVE: To assess the efficacy of percutaneous laser disc decompression for patients with radicular pain due to lumbar disc hernia and to identify factors that may predict outcome. METHODS: The study included all patients treated with percutaneous laser disc decompression from May 2003 through May 2005 at Reims University Hospital and the Courlancy Clinic of Reims. Each patient had previous undergone at least six weeks of conventional medical treatment. The same technique, with either a laser diode or Nd: YAG, was used under endoscopic control and with neuroleptanalgesia. They were seen at 1, 3, 6 and 12 months. The principal evaluation criteria were the course of radicular pain, return to work, and need for surgery. RESULTS: We reexamined 149 patients 1 month after the procedure, 135 after 3 months, 102 after 6 months and 59 a year after the procedure. At a month after surgery, radicular pain had decreased by at least half, and sometimes even completely disappeared in 63.1% of patients at 1 month, 66.6% at 3 months, 73.5% at 6 months, and 83.1% at 12 months, while 24%, 50,4%, 61.2%, and 67.3%, respectively, had returned to work. No patient had serious complications. Finally, 45 of the 149 (30.2%) patients chose to have a traditional surgical procedure after percutaneous laser disc decompression. CONCLUSION: Percutaneous laser disc decompression is effective, noninvasive and well tolerated for patients with radicular pain due to lumbar disc hernia.

Disease-modifying anti-rheumatic drug effect of denosumab on radiographic progression in rheumatoid arthritis: a systematic review of the literature.

The aim of this study was to evaluate the structural effect of denosumab on patients with rheumatoid arthritis (RA). We performed a systematic review of the literature in the following databases: PubMed, Cochrane, Web of Science, ClinicalTrials.gov , and the WHO International Clinical Trials Registry Platform. All studies evaluating the structural effect of denosumab on RA and meeting predefined criteria were included. Data regarding disease activity, progression of joint damage, joint space narrowing, and safety were recorded. Among 168 studies identified, only 4 were finally included in this review, involving a total of 687 patients. These 4 studies showed that denosumab is effective on joint damage at 6 and 12 months as compared to placebo, alendronate, and biological disease-modifying anti-rheumatic drugs (bDMARDs) alone. No effect was observed in terms of joint space narrowing, and DAS28 and HAQ scores remained unchanged. No case of osteonecrosis of the jaw or atypical fracture was recorded, and safety was similar in both denosumab and control groups. Denosumab appears to be effective on joint erosion at 6 and 12 months in patients with RA meeting the ACR criteria, treated or not by a biologic, with excellent safety.

[Tuberculosis during treatment by TNFalpha-inhibitors]. / Tuberculose lors d'un traitement par agents inhibiteurs du TNF alpha.

The clinical forms of tuberculosis that occur during anti-TNFalpha treatment are frequently extrapulmonary or even disseminated and life-threatening. The paradoxical reactions that can occur under appropriate treatment after stopping TNFalpha inhibitors raise the question of an immune restoration phenomenon. Adverse drug reaction reporting and epidemiologic studies, despite their methodological limitations, appear to show an excess risk of tuberculosis. Experimental studies reinforce these data. The French drug agency (Afssaps) has issued guidelines for the prevention and management of tuberculosis occurring under anti-TNFalpha treatment. Analogous guidelines in Spain led to a reduction in the incidence of these cases.

Diagnostic contribution of a second percutaneous needle biopsy in patients with spontaneous diskitis and negative blood cultures and first biopsy.

OBJECTIVES: The primary objective was to assess the diagnostic contribution of a second percutaneous needle biopsy in patients with spontaneous diskitis and negative findings from blood cultures and the first biopsy. We also assessed the sensitivity of the first biopsy and the diagnostic contribution of post-biopsy blood cultures. METHODS: Multicenter retrospective study of patients managed between 2004 and 2014. We excluded patients with postoperative diskitis. RESULTS: We identified 63 patients with spontaneous diskitis, negative blood cultures, and at least one percutaneous needle biopsy during the study period. The first biopsy established the diagnosis in 33 (52%) patients. Of the 30 remaining patients, 10 (33%) had a second biopsy, which was positive in 6 (60%), and 20 (67%) received probabilistic antibiotic therapy. There were 8 positive blood cultures after the first biopsy but, among them, 7 occurred in biopsy-positive patients. Biopsy yield varied with the guidance method (needle guidance software or imaging by computed tomography and/or fluoroscopy) and operators. Antibiotic therapy within the 6months preceding the first biopsy was significantly associated with having a negative first biopsy (15/30 versus 7/33; odds ratio, 3.13; 95% confidence interval, 1.07-9.13; P<0.05). CONCLUSION: In our study, a second needle biopsy was useful, providing the bacteriological diagnosis in 60% of cases of spontaneous diskitis with negative findings from blood cultures and the first biopsy.

Factors useful for predicting survival of myeloma patients in everyday practice. A 10-year study of 148 patients older than 55 years.

OBJECTIVE: The objective of this study was to identify prognostic factors in a uniform population of older patients with myeloma. METHODS: Thirty-one study centers in France included 148 patients who were older than 55 years at diagnosis and were followed up until death or for at least 10 years. The following tests were available for all patients: blood cell counts; serum, and urinary protein electrophoresis; and serum levels of creatinine, calcium, beta2 microglobulin (beta2m), lactic dehydrogenase (LDH), and C-reactive protein (CRP). RESULTS: Mean age was 71.9 years, median survival was 34 months, and mean survival was 47 months. In the univariate analysis, factors significantly associated with higher mortality were male gender (odds ratio [OR], 1-2.12), age older than 70 years (OR, 1.10-2.28), serum albumin<30 g/l (OR, 1.16-3.28), serum creatinine>100 micromol/l (OR, 1.34-2.81), beta2m>6 mg/l (OR, 1.78-4), CRP>6 mg/l (OR, 1.44-3.06), hemoglobin<10 g/dl (OR, 1.8-2.23). In the multivariate analysis, only two factors significantly predicted a higher risk of death: beta2m>6 mg/l (OR=2.439 [1.59-3.76]) and CRP>6 mg/l (OR=1.76 [1.18-2.63). beta2m level was >6 mg/l in 41 (27.7%) patients and CRP was >6 mg/l in 61 (43.6%) patients. Other potential prognostic factors such as chromosome 13 deletion were not investigated because they were not available for all study patients. CONCLUSIONS: The strength of this study is the 10-year follow-up in a uniform patient cohort. beta2m and CRP independently predicted the risk of death.

Tonic dystonia: an uncommon complication of reflex sympathetic dystrophy syndrome. A review of five cases.

Tonic dystonia is an underrecognized complication of reflex sympathetic dystrophy syndrome (RSDS) characterized by an increase in muscle tone at the site of injury. Case-reports.- We describe five cases of tonic dystonia complicating RSDS of the lower extremity. There were four women and one man, with a mean age of 52 years. In addition to the typical features of RSDS, the patients had fixed equinovarus of the foot with hyperextension or hyperflexion of the great toe. In two patients, examination after spinal anesthesia showed that the deformity was reducible. Spontaneous resolution of the dystonia occurred in one patient. Another patient failed to experience meaningful improvement after a motor block followed by botulinic toxin injections. In two patients, the same treatment was followed by a slight improvement. Treatment options are still being evaluated in the last patient. Discussion.- Tonic dystonia is an underrecognized complication of RSDS that often develops after a minor injury yet causes prolonged pain and disability. Spread of the dystonia to other sites is not infrequent. The underlying mechanisms remain unclear but may involve dysfunction of the central or peripheral nervous system or psychogenic factors. Suggested treatments include motor block, intrathecal baclofen, sympathetic block, and sympathectomy. However, none of these treatments has been proved effective. Conclusion.- The five cases described here provide useful information on RSDS-associated tonic dystonia, a condition that runs a protracted course and remains difficult to manage.

Pituitary involvement in granulomatosis with polyangiitis: report of 9 patients and review of the literature.

Pituitary dysfunction is a rare manifestation of granulomatosis with polyangiitis (GPA) (Wegener). The main aim of this multicenter retrospective study was to describe the characteristics and outcomes of pituitary manifestations in patients with GPA included in the French Vasculitis Study Group database.Among the 819 GPA patients included in the database, 9 (1.1%) had pituitary involvement. The median age at diagnosis of GPA and pituitary involvement was 46 and 50.8 years, respectively. Pituitary involvement was present at onset of GPA in 1 case and occurred later in 8 patients after a median follow up of 58.5 months. When pituitary dysfunction occurred, 8 patients had active disease at other sites including ENT (n = 6), eye (n = 4), or central nervous system (n = 3) involvement. The most common hormonal dysfunctions were diabetes insipidus (n = 7) and hypogonadism (n = 7). Magnetic resonance imaging was abnormal in 7 patients. The most common lesions were an enlargement of the pituitary gland, thickening of the pituitary stalk, and loss of posterior hypersignal on T1-weighed images. All patients were treated with corticosteroid therapy and 8 patients received immunosuppressive agents for the pituitary involvement, including cyclophosphamide (n = 3), rituximab (n = 2), and methotrexate (n = 3). After a median follow-up of 9.2 years, GPA was in complete remission in 7 patients, but 8 patients were still under hormone replacement therapy. Among the 5 patients who had a subsequent MRI, 2 had complete resolution of pituitary lesions.By combining our study and the literature review, the frequency of hypogonadism and diabetes insipidus, among the patients with pituitary dysfunction, can be estimated at 78% and 71% respectively. Despite a high rate of systemic disease remission on maintenance therapy, 86% of the patients had persistent pituitary dysfunction. The patients who recovered from pituitary dysfunction had all been treated by cyclophosphamide.Pituitary disease in GPA occurs mostly several months or years after diagnosis. There is no correlation between hormonal, radiologic, and systemic outcome. Although immunosuppressive drugs improve the systemic disease, hormonal deficiencies usually persist. It is therefore important to shorten diagnostic delays and treat these patients early in the course of disease before irreversible damage occur.

Discitis and sacroiliitis diagnosed 15 years after iatrogenic Mycobacterium xenopi inoculation.

A patient was diagnosed with discitis and sacroiliitis due to Mycobacterium xenopi. He had a history of percutaneous nucleotomy performed 15 years earlier (in 1992) at the Clinique du Sport, Paris, France, during an outbreak of nosocomial M. xenopi infection at that institution. In 1997, magnetic resonance imaging performed as part of the routine follow-up program for patients who had surgery at the Clinique du Sport during the outbreak was not interpreted as indicating discitis; this assessment was confirmed by our review of the images. Bone and joint infections due to atypical mycobacteria are rare and can develop very slowly. To our knowledge, this is the first reported case of M. xenopi discitis with secondary extension to the sacroiliac joint in an immunocompetent patient.