Baden-Baden, Germany
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Chines A.A.,Pfizer | Palacios S.,Palacios Institute of Womens Health | Lips P.,VU University Amsterdam | Levine A.B.,Pfizer | And 3 more authors.
Osteoporosis International | Year: 2011

Summary: Findings from this 5-year phase 3 study of postmenopausal women with osteoporosis showed that bazedoxifene was associated with an overall favorable safety and tolerability profile, with no evidence of endometrial or breast stimulation. Overall, the results at 5 years were consistent with those seen at 3 years. Introduction: We report safety and tolerability findings from a 5-year randomized, double-blind, phase 3 study of bazedoxifene in postmenopausal women with osteoporosis. Methods: In the core study, healthy postmenopausal women with osteoporosis (N=7,492; mean age, 66.4 years) were randomized to daily doses of bazedoxifene 20 or 40 mg, raloxifene 60 mg, or placebo for 3 years. During the 2-year study extension, the raloxifene 60-mg treatment arm was discontinued after the 3-year database was finalized, and subjects receiving bazedoxifene 40 mg were transitioned in a blinded manner to bazedoxifene 20 mg (bazedoxifene 40-/20-mg group) after 4 years. Safety and tolerability data are reported for subjects in the bazedoxifene 20- and 40-/20-mg and placebo groups; efficacy findings are reported elsewhere. Results: A total of 3,146 subjects in the bazedoxifene 20- and 40-mg and placebo groups were enrolled in the extension study (years 4 and 5). Overall, the 5-year incidence of adverse events (AEs), serious AEs, and discontinuations due to AEs were similar among groups. The incidence of hot flushes and leg cramps was higher with bazedoxifene compared with placebo. Venous thromboembolic events, primarily deep vein thrombosis, were more frequently reported in the bazedoxifene groups compared with the placebo group. Reports of cardiac disorders and cerebrovascular events were few and evenly distributed among groups. Bazedoxifene showed a neutral effect on the breast and endometrium. Conclusion: Bazedoxifene was associated with an overall favorable safety and tolerability profile in postmenopausal women with osteoporosis over 5 years of therapy, consistent with findings at 3 years. © 2010 International Osteoporosis Foundation and National Osteoporosis Foundation.


Chopra A.,Center for Rheumatic Diseases
Indian Journal of Rheumatology | Year: 2015

The maiden WHO ILAR COPCORD (community oriented program for control of rheumatic diseases) Bhigwan (1996-2014) demonstrated that musculoskeletal (MSK) pain was the commonest self-reported ailment in the community, soft tissue rheumatism, ill-defined MSK symptoms and osteoarthritis (OA) were the predominant disorders and about 10% cases suffered from inflammatory arthritis. The burden of rheumatoid arthritis (RA) was high with point prevalence of 0.7%. Bone and joint decade (BJD) India conducted several standardized and uniform surveys (2004-2010) all over India and collected data from over 55,000 persons at 12 sites. The pooled age sex adjusted (India census population 2001) prevalence reported by the recent surveys was - RA (0.34), OA knees (3.34), undifferentiated inflammatory arthritis (0.22), Spondyloarthritis (0.23), ankylosing spondylitis (0.03), psoriatic arthritis (0.01) soft tissue rheumatism (1.39), gout (0.05) lupus (0.01); prevalence percent in parenthesis. Several forms of collagen vascular disorders and vasculitis are described in hospital based case series. Musculoskeletal infections including tuberculosis remain an important clinical burden. The 2006 India Chikungunya epidemic has put an additional burden of chronic MSK pain and arthritis. The recently launched national health programs pertaining to non-communicable diseases, rural and women health does not even mention rheumatic diseases thus there is urgent need to study the burden of rheumatic diseases and its impact on society. © 2015 Indian Rheumatology Association. All rights reserved.


Chopra A.,Center for Rheumatic Diseases | Anuradha V.,Center for Rheumatic Diseases | Ghorpade R.,Center for Rheumatic Diseases | Saluja M.,Center for Rheumatic Diseases
Epidemiology and Infection | Year: 2012

Chikungunya virus (CHIKV) data from population studies are sparse. During the 2006 epidemic, 509 clinical cases (43% attack rate) were identified in a village survey (West India); laboratory investigations demonstrated normal blood cell counts, elevated acute-phase reactants [erythrocyte sedimentation rate, C-reactive protein and interleukin-6 (IL-6)] and excluded malaria and dengue. Acute CHIKV was characterized by high fever, severe peripheral polyarthralgias, axial myalgias and intense fatigue in over 90% of cases; skin rash (34%) and headache (19%) were uncommon. There were 49% and 62% of survey cases seropositive for IgM (rapid assay) and IgG (immunofluorescence) anti-CHIKV antibodies, respectively. Sixty-five percent of cases recovered within 4 weeks. None of the cases died. Of the population, 41% and 16% suffered from persistent rheumatic pains, predominantly non-specific, at 1 and 2 years, respectively. Chronic inflammatory arthritis was uncommon (03% at 1 year) although serum IL-6 often remained elevated in chronic cases. A larger population study is required to describe post-CHIKV rheumatism and its prognosis. © Copyright Cambridge University Press 2011.


Kunjir V.,Center for Rheumatic Diseases | Venugopalan A.,Center for Rheumatic Diseases | Chopra A.,Center for Rheumatic Diseases
Journal of Rheumatology | Year: 2010

Objective. To assess the current International League of Associations for Rheumatology (ILAR) classification criteria (Edmonton, 2001) for juvenile idiopathic arthritis (JIA) in Indian patients. Methods. Out of 441 children, 330 with chronic joint pains were diagnosed with juvenile onset chronic inflammatory arthritis and followed in an observational cohort. Our study was carried out from 1994 to 2006 in a community rheumatology clinic. Emphasis was placed on obtaining data required by the ILAR system. Of the original group, 235 children were eventually classified as having JIA; 108 were examined during the first year of illness. Results. We assigned 224 children (95%) to discrete JIAcategories: enthesitis-related arthritis (ERA; 36%), oligoarthritis (OLA-persistent; 17%), polyarthritis rheumatoid factor (RF)-negative (17%), polyarthritis RF-positive (12%), systemic arthritis (8%), OLA-extended (4%), and psoriatic arthritis (1%). The remaining 11 children (5%) were classified with undifferentiated arthritis (mostly an overlap due to seropositive RF and/or HLA-B27). The prevalence of ERA(89% HLA- B27-positive) and seropositive RF was unexpectedly high. Although agreement (κ > 0.79) with the American College of Rheumatology criteria and the European Spondylarthropathy Study Group criteria was good to excellent, the ILAR system was found to be more comprehensive and clinically homogeneous. However, some problems appear unique in our scenario. Conclusion. A wide-spectrum phenotype of JIA is demonstrated by an Indian cohort. Although useful, RF and HLA-B27 in this population proved problematic to the ILAR classification. The Journal of Rheumatology Copyright © 2010. All rights reserved.


Venugopalan A.,Center for Rheumatic Diseases | Ghorpade R.P.,Center for Rheumatic Diseases | Chopra A.,Center for Rheumatic Diseases
PLoS ONE | Year: 2014

Introduction: Acute chikungunya (CHIKV) is predominantly an acute onset of excruciatingly painful, self-limiting musculoskeletal (MSK) arbovirus illness and this was further reported by us during the 2006 Indian epidemic [Chopra et al. Epidemiol Infect 2012]. Selected serum cytokines profile in subjects within one month of onset of illness is being presented. Methods: Out of 509 clinical CHIKV cases (43% population) identified during a rural population survey, 225 subjects consented blood investigations. 132 examined within 30 days of febrile onset are the study cohort. Anti-CHIKV IgM and IgG antibodies tested by immunochromatography and indirect immunofluorescence respectively. Interferons (IFN)-α, -β and -γ, Interferon Gamma-Induced Protein-10 (CXCL-10/IP-10), Tumor Necrosis Factor-α (TNF-α), Interleukin-1β (IL-1β ), Interleukin-6 (IL-6), Interleukin-13 (IL-13), Monocyte Chemoattractant Protein-1 (MCP-1), Interleukin-4 (IL-4) and Interleukin-10 (IL-10) performed by ELISA. Samples collected from neighboring community a year prior to the epidemic used as healthy controls. Results: Seropositivity for anti-CHIKV IgM and IgG was 65% and 52% respectively. IFN-α, IFN- β, IFN-γ, CXCL10/IP-10 and IL-1β showed intense response in early acute phase. Cytokines (particularly TNF-α, MCP-1, IL-4, IL-6 and IL-10) was maximum in extended symptomatic phase and remained elevated in recovered subjects. Higher (p〈0.05) IFN and IL-4 seen in patients seropositive for anti-CHIKV IgG. Elderly cases (≥65 years) showed elevated cytokines (except IFN) and anti-CHIKV antibodies near similar to younger subjects. Significant correlations (p〈0.05) found between cytokines and clinical features (fatigue, low back ache, myalgia) and anti-CHIKV antibodies. Conclusion: An intense cytokine milieu was evident in the early and immediate persistent symptomatic phase and in recovered subjects. Early persistent IgM and lower IgG to anti-CHKV and intense Th2 cytokine phenotype seem to be associated with delay in resolution of MSK symptoms. Intriguingly, maximum TNF-α, IL-6 and IL-13 with low anti-CHIKV IgM response found in subjects recovered from CHIKV within one month of illness. © 2014 Venugopalan et al.


Chopra A.,Center for Rheumatic Diseases | Saluja M.,Center for Rheumatic Diseases | Venugopalan A.,Center for Rheumatic Diseases
Arthritis and Rheumatology | Year: 2014

Objective. To evaluate whether chloroquine (CQ) is more effective than meloxicam for treating early musculoskeletal pain and arthritis following acute chikungunya (CHIK) virus infection. Methods. During the 2006 CHIK epidemic, 509 rural community cases of acute CHIK virus infection were identified in the district of Sholapur in India. Seventy consenting adult patients (seropositive for IgM/ IgG anti-CHIK antibody) with early persistent musculoskeletal pain and arthritis were randomized into a 24-week, 2-arm, parallel efficacy trial of CQ (250 mg/ day) and meloxicam (7.5 mg/day). Assessors completed a rheumatology evaluation in a blinded manner and collected blood samples in the patients' homes, as per protocol. Laboratory parameters included serum cytokine assay (interleukin-6 [IL-6], interferon-γ [IFNγ], tumor necrosis factor α, CXCL10/IFNγ-inducible protein 10, and IL-13). Twenty-two patients who failed to meet the eligibility criteria (low pain cohort) were also followed up with similar evaluations. An intent-to-treat analysis was completed. At baseline, the 2 groups (38 patients randomized to receive CQ and 32 patients randomized to receive meloxicam) were well matched. Results. There were no significant efficacy differences between the meloxicam group and the CQ group (mean changes in the visual analog scale score for pain -3.9 and -4.2, respectively). Patients improved significantly. Cytokine levels remained several-fold increased, were disproportionate to the clinical response, and were not different from those in the low pain cohort. Seven patients withdrew. Adverse events were mild and infrequent. Conclusion. This exploratory community intervention trial failed to identify an advantage of CQ over meloxicam to treat early musculoskeletal pain and arthritis following acute CHIK virus infection, but therapeutic efficacy of CQ was not ruled out. The inflammatory cytokine response was intense and was not consistent with clinical status. © 2014, American College of Rheumatology.


Chopra A.,Center for Rheumatic Diseases | Saluja M.,Center for Rheumatic Diseases
Indian Journal of Rheumatology | Year: 2012

Background: Stanford HAQ (S-HAQ) and several versions are used worldwide to measure physical function. Based on traditions and life style, a maiden Indian version (CRD Pune) was developed and used extensively (1996-2011). We report clinimetric properties and long term use. Methods: The Indian version was finalized in a step wise consensus building process between doctors, community and patients. It remained similar to S-HAQ in basic structure (categories) and score/disability index. Current data was selected from controlled drug trials in active RA, referral community patients (clinic and camps) and WHO ILAR COPCORD (community oriented program for control of rheumatic diseases) Bhigwan. Standard statistics were used; significant p < 0.05. Results: Test-retest and correlation statistics confirmed face and content (Cronbach's index >0.8) and construct validity and reliability at several time points. There was fair to good (0.2-0.6) correlation between Indian HAQ and pain visual analog scale, joint counts for pain/tenderness and swelling, sedimentation rate and radiological score (joint damage). The efficacy variables explained up to 70% variation in HAQ (dependent) regression models. The Indian HAQ scored significantly higher than the S-HAQ but the difference was not clinically relevant. The Indian HAQ was sensitive to change (effect size 0.7) over 24 week treatment with hydroxychloroquin. Generic use in COPCORD survey showed moderately severe HAQ disability in all patient groups including 'ill-defined aches' and soft tissue rheumatism. HAQ improved patient satisfaction. Conclusion: The Indian HAQ (CRD Pune) was a valid and useful patient outcome measure and improved compliance (long term follow up). © 2012, Indian Rheumatology Association. All rights reserved.


Swart A.,Center for Rheumatic Diseases | Burlingame R.W.,INOVA Diagnostics Inc. | Gurtler I.,Center for Rheumatic Diseases | Mahler M.,INOVA Diagnostics Inc.
Clinica Chimica Acta | Year: 2012

Introduction: We compared 2 anti-citrullinated protein antibody (ACPA) assays using a routine patient cohort. Methods: Two-hundred ninety-five sera were collected from patients for whom ACPA was ordered and tested for ACPA by QUANTA Lite® CCP 3 (INOVA Diagnostics, Inc., San Diego) and EliA® CCP (CCP, Phadia, Germany). Rheumatoid factor (RF) was determined using Quantex RF(II) (Biokit, Spain). Results: Acceptable qualitative (96.6%, kappa. =. 0.93) and quantitative agreements (Spearman rho. =. 0.77; p<. 0.0001) were observed between the two ACPA assays. Nine samples were CCP3. +/CCP2. - and one sample was CCP2. +/CCP3. -. Of the 9 CCP3. +/CCP2. - patients, 6 (66.7%) had RA, one patient had ankylosing spondylitis, one osteoarthritis and one psoriatic arthritis. The CCP3. -/CCP2. + patient had juvenile RA. At the manufacturer's cut-offs, the sensitivities and specificities were 77.3%/98.1% (CCP2), 81.6%/96.8% (CCP3) and 65.2%/89.6% (RF), respectively. At 98.7% specificity level, the sensitivities in the total cohort were 59.6% (CCP2) and 69.5% (CCP3) while the sensitivities in the RF-negative group were 49.0% (CCP2) and 57.1% (CCP3).In the RF-negative group, sensitivities for patients with a disease duration of ≤. 5. years were 38.7% (CCP2) and 51.6% (CCP3). Conclusion: Discrimination between RA and non-RA patients was better using CCP3, most pronounced in RF-negative RA. © 2012 Elsevier B.V.


Xanthouli P.,Center for Rheumatic Diseases | Sailer S.,Center for Rheumatic Diseases | Fiehn C.,Center for Rheumatic Diseases
Open Rheumatology Journal | Year: 2012

Objectives: The use of TNF-alpha antagonists may be associated with an increased rate of infections in risk populations of patients with RA. Our hypothesis was that in patients with a high risk of infection Rituximab (RTX) could be a safer alternative. Methods: We analyzed the outcome of RA patients who received RTX instead of TNF-alpha antagonist because of a history of serious infections or frequent infectious events. All patients in a given time period were included in the retrospective analysis. Results: 32 patients were identified according to the above criteria and followedup for a mean period of 16 ± 8 months (range 6 - 36) during treatment with RTX. Only one patient was lost to follow-up. Sixteen patients were anti-TNF-naïve and in the remaining patients the TNF-alpha antagonist was stopped due to infectious complications before starting RTX. RTX was combined with a disease modifying drug in 22 (69%) of the cases. Altogether 4 severe infections occurred (9.5/100 patient years), mainly within the first year of treatment with RTX. Two patients suffered from pneumonia, 1 from a postoperative wound infection, 1 from an ear abscess and bacterial bronchitis. None of our patients with a previous history of bacterial infections of soft tissue, bacterial arthritis or osteomyelitis (n=9) developed recurrent infection. No relapse of a previously diagnosed tuberculosis (n=9) was seen. Conclusions: In this particular high risk population of RA patients, treatment with RTX seems to be an alternative to TNF-alpha-antagonist and has a relatively low rate of recurrent infection. © Xanthouli et al.


Codreanu C.,Center for Rheumatic Diseases | Enache L.,Center for Rheumatic Diseases
Medical Ultrasonography | Year: 2015

Ultrasonography (US) is widely used in the diagnosis of rheumatic conditions, and its value for the classification criteria of rheumatic diseases has been recently suggested. According to the EULAR/ACR provisional criteria for polymyalgia rheumatica, adding US to the clinical and serological features will significantly improve the sensitivity of proposed criteria. The ability of high resolution US to detect crystalline deposits of monosodium urate in joints and soft tissues is well recognized. For the first time, the new 2014 ACR/EULAR set of proposed criteria for gout includes advanced imaging techniques for the detection of disease: US and dual-energy computed tomography. Due to low costs and affordability, use of US evaluation for patients with suspected gout will increase both specificity and sensibility of classification criteria. The recent inclusion of US in the classification criteria of various rheumatic diseases, such as PMR and gout, implies that this imaging technique is not only useful as a valued diagnostic tool for individual cases, but also on a larger scale, it will improve doctors' ability to classify diseases. Its use is thus changing our understanding of rheumatic diseases allowing further advances in research and clinical practice.

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