The Physical and Psychosocial Impact of Fatigue among Patients with Sjogren's Syndrome: A Systematic Review.

Background: Primary Sjögren's syndrome (pSS) is a complex autoimmune disorder characterized by organ-specific symptoms in the salivary and lacrimal glands, as well as systemic manifestations. Fatigue, a prominent aspect, significantly influences the overall quality of life for individuals with pSS. Methods: This review seeks to evaluate the impact of fatigue by exploring its consequences, potential causes, and effects on physical and psychological well-being, while also investigating its management strategies. Following the "Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)" guidelines, our systematic literature review involved a five-step algorithm. Initially identifying 78 articles in reputable international medical databases, we applied eligibility criteria and removed duplicates, resulting in 19 articles for qualitative synthesis. Results: This review delves into the predictive factors for heightened fatigue in pSS, encompassing rheumatoid factor levels, erythrocyte sedimentation rate, and immunoglobulin G levels. Sleep disturbances, specifically nighttime pain and nocturia, emerged as determinants of persistent daytime fatigue. Cognitive impairment in pSS involves deteriorations in global memory, executive functioning, and attentional resources. Furthermore, functional limitations in pSS impact patients' quality of life. Conclusions: The significance of fatigue in pSS, its consequences, and profound influence on the quality of life necessitate further research for a more comprehensive understanding of this complex issue.

Paraneoplastic Polyarthritis in a Patient with Synchronous Lung and Colorectal Malignancy.

Arthritis is an unusual manifestation of paraneoplastic syndrome, appearing in a variety of cancers, including pulmonary and colorectal. It can often pose a diagnostic challenge to physicians, since it may be difficult to distinguish from more commonly encountered rheumatic illnesses. Moreover, synchronous cancers are rare and unexpected in patients with symmetrical polyarthritis. Hypertrophic pulmonary osteoarthropathy is to be considered in patients with polyarthritis and lung neoplasia. The aim of this report is to highlight the case of a patient presenting with paraneoplastic polyarthritis, which led to identifying the presence of underlying synchronous lung and colorectal malignancies. Lymph node biopsy was performed raising suspicion of Caplan's syndrome but lung lobectomy confirmed adenocarcinoma. Rheumatologists should be reacquainted with rheumatic manifestations in malignant diseases.

A "Mix and Match" in Hemochromatosis-A Case Report and Literature Focus on the Liver.

Hemochromatosis is a genetic disorder characterized by increased iron storage in various organs with progressive multisystemic damage. Despite the reports dating back to 1865, the diagnosis of hemochromatosis poses a challenge to clinicians due to its non-specific symptoms and indolent course causing significant delay in disease recognition. The key organ that is affected by iron overload is the liver, suffering from fibrosis, cirrhosis or hepatocellular carcinoma, complications that can be prevented via early diagnosis and treatment. This review aims to draw attention to the pitfalls in diagnosing hemochromatosis. We present a case with multiorgan complaints, abnormal iron markers and a consistent genetic result. We then examine the relevant literature and discuss hemochromatosis subtypes and liver involvement, including transplant outcome and treatment options. In summary, hemochromatosis remains difficult to diagnose due to its symptom heterogeneity and rarity; thus, further education for practitioners of all disciplines is useful in facilitating its early recognition and management.

Refractory Takayasu's Arteritis with Severe Coronary Involvement-Case Report and Literature Review.

This report presents the case of a female patient diagnosed with Takayasu arteritis from childhood, with severe, refractory coronary involvement, leading to two acute coronary syndromes and multiple anginous episodes. Consequently, the patient suffered aorto-bicarotid bypass two times, multiple interventional procedures with stent implantation, balloon angioplasty, and up to ten repeated in-stent restenosis that required reinterventions, despite being on maximal immunosuppressive treatment. In recent years, various studies have been reported that aim to best characterize this particular type of vascular damage and to indicate optimal therapeutic options for treatment. The latter should be based on the activity of the underlying disease; however, no reliable markers are available in TA. The management of TA patients with coronary involvement continues to be a challenge and requires both drug and interventional techniques to avoid life-threatening events.

Eosinophilic Fasciitis: Current and Remaining Challenges.

Eosinophilic fasciitis (EF), defined as diffuse fasciitis with eosinophilia by Shulman in 1974, is a disease with unknown etiology and whose pathogenesis is still being researched. The diagnosis is based on the clinical aspects (skin induration with an "orange peel" appearance), the lab results (eosinophilia, increased inflammatory markers), the skin biopsy with the pathognomonic histopathological result, as well as the typical MRI changes. The treatment includes glucocorticoids and immunosuppressive drugs. Due to severe refractory cases, the treatment remains a challenge. EF is still a disease with potential for further research.

Preparing for Pregnancy in Women with Systemic Lupus Erythematosus-A Multidisciplinary Approach.

Pregnancy is one of the most challenging processes the human body is exposed to: the healthy mother can carry to term a genetically different new-born, while her immune system adapts to tolerate this new status and avoids rejection. In autoimmune disorders, motherhood is even more challenging, with additional medical counselling, mother care, and foetus development checks being necessary. While the aspects of supplementary mother care and pregnancy progress tracking are associated with well-established medical procedures and protocols, counselling, be it pre- or post-conception, is still underestimated and scarcely applied. Indeed, over the past decades, medical counselling for this particular population has changed significantly, but from a healthcare's provider point of view, more is required to ensure a smooth, controllable pregnancy evolution. One of the most frequent autoimmune diseases affecting young females during their fertile years is Systemic Lupus Erythematosus (SLE). Like other heterogenous diseases, it exposes the mother to severe, organ-threatening complications and unpredictable evolution. Both the disease and its treatment can significantly affect the mother's willingness to engage in a potentially risky pregnancy, as well as the likeliness to carry it to term without any impairments. A good collaboration between the patient's rheumatologist and obstetrician is therefore mandatory in order to: (a) allow the mother to make an informed decision on pursuing with the pregnancy; (b) ensure a perfect synchronization between pregnancy terms and treatment; and (c) avoid or minimize potential complications. The best approach to achieve these outcomes is pregnancy planning. Moreover, knowing one desired prerequisite for a successful pregnancy evolution in SLE mothers is a stable, inactive, quiescent disease for at least six months prior to conception, planning becomes more than a recommended procedure. One particular aspect that requires attention before conception is the treatment scheme applied before delivery as autoantibodies can influence significantly the course of pregnancy. In this view, future SLE mothers should ideally benefit from preconception counselling within their agreed care pathway. A multidisciplinary team including at least the rheumatologist and obstetrician should be employed throughout the pregnancy, to decide on the appropriate timing of conception and compatible medication with respect to disease activity, as well as to monitor organ involvement and foetus development progress.

Infections in patients with rheumatoid arthritis receiving tofacitinib versus tumour necrosis factor inhibitors: results from the open-label, randomised controlled ORAL Surveillance trial.

OBJECTIVES: To characterise infections in patients with rheumatoid arthritis (RA) in ORAL Surveillance. METHODS: In this open-label, randomised controlled trial, patients with RA aged≥50 years with ≥1 additional cardiovascular risk factor received tofacitinib 5 or 10 mg two times per day or a tumour necrosis factor inhibitor (TNFi). Incidence rates (IRs; patients with first events/100 patient-years) and hazard ratios (HRs) were calculated for infections, overall and by age (50-<65 years; ≥65 years). Probabilities of infections were obtained (Kaplan-Meier estimates). Cox modelling identified infection risk factors. RESULTS: IRs/HRs for all infections, serious infection events (SIEs) and non-serious infections (NSIs) were higher with tofacitinib (10>5 mg two times per day) versus TNFi. For SIEs, HR (95% CI) for tofacitinib 5 and 10 mg two times per day versus TNFi, respectively, were 1.17 (0.92 to 1.50) and 1.48 (1.17 to 1.87). Increased IRs/HRs for all infections and SIEs with tofacitinib 10 mg two times per day versus TNFi were more pronounced in patients aged≥65 vs 50-<65 years. SIE probability increased from month 18 and before month 6 with tofacitinib 5 and 10 mg two times per day versus TNFi, respectively. NSI probability increased before month 6 with both tofacitinib doses versus TNFi. Across treatments, the most predictive risk factors for SIEs were increasing age, baseline opioid use, history of chronic lung disease and time-dependent oral corticosteroid use, and, for NSIs, female sex, history of chronic lung disease/infections, past smoking and time-dependent Disease Activity Score in 28 joints, C-reactive protein. CONCLUSIONS: Infections were higher with tofacitinib versus TNFi. Findings may inform future treatment decisions. TRIAL REGISTRATION NUMBER: NCT02092467.

Paget's disease of bone and megaloblastic anemia in a 72-year-old patient: A case report and systematic literature review.

Paget's disease of bone (PDB) is characterized by abnormal osteoclastic bone resorption with disorganized bone neo-formation, primarily affecting elderly (>55 years) patients. Although the majority of patients are asymptomatic, some patients may experience bone pain due to local periosteal involvement or osteoarthritic lesions in the spine; in addition, limb deformities may lead to secondary gait problems or degenerative joint changes. Anemia has an overall prevalence of 12-17% in elderly adults (>65 years old), with macrocytic anemia being the less common type. Megaloblastic anemia is a macrocytic anemia characterized by the presence of large, immature, nucleated cells (megaloblasts) in the blood, with the most common cause being a deficiency of folate and/or vitamin B12. We herein report the rare case of a 72-year-old male patient exhibiting both these conditions, with the aim of discussing the possible association between the two and, most importantly, the clinical management of the patient in a real-life setting over a period of 10 years. The patient was diagnosed based on clinical symptoms (bone pain), radiological imaging and specific laboratory tests, and received discontinuous courses of bisphosphonates and cyanocobalamin supplementation therapy, based mainly on aggravated symptomatology. A systematic literature review was also performed and revealed not only the scarcity of reports on similar cases, but also the mechanisms that may underlie the possible association of PDB with macrocytic anemia due to vitamin B12 deficiency in elderly patients.

Translation and cultural adaptation of a romanian version of the communication assessment tool (CAT_Ro).

BACKGROUND: The communication between health providers and patients influences the quality of medical care. The Communication Skills Assessment (CAT) is a reliable, validated tool, which was developed to assess interpersonal communication skills between physicians and patients. The purpose of this study was to obtain a Romanian version of the CAT (CAT_Ro), using a controlled and systematic process to translate and cross-culturally adapt the original questionnaire, since there are no validated instruments to assess healthcare professionals' communication capability in Romania. METHODS: The study was conducted in two Departments of Internal Medicine and Rheumatology from Bucharest, Romania, using a rigorous scientific methodology for the translation process, according to literature recommendations, implicating conceptual evaluation, semantics, and cultural adaptation, which involved several steps. The updated version was pre-tested in a pilot study, which included 89 outpatients. RESULTS: The results showed a narrow range of variability in item interpretation, without differences in patients' responses according to variables such as age, gender, education, disease type, number of previous visits with the same doctor. CONCLUSION: CAT-Ro is the result of a comprehensive process study. It represents the first translation and cultural adaptation in Romanian of an instrument able to assess the health providers' communication skills, which was validated in a pilot study and is to be used in more extensive studies with patients from several specialties.

Characteristics of shared decision making in Romania from the patient perspective: A cross-sectional multicentric study.

BACKGROUND: Shared decision making (SDM) is very important from patients' perspective. This process has not yet been evaluated in Romania. The study aims to evaluate SDM from the patients' perspective and to evaluate patients' characteristics that associate with SDM. MATERIAL AND METHODS: A cross-sectional multicentric study comprising eight recruitment centres was performed. Inpatients and outpatients who referred to Hospital Units treating autoimmune diseases or atrial fibrillation were included. Another sample consisted of members of the Autoimmune Disease Patient Society, who completed an online anonymous questionnaire. All participants completed the Romanian translated version of the 9-item Shared Decision Making Questionnaire (SDM-Q-9), as these samples were used for the validation of this questionnaire, too. Patients had to refer to the visit in which the decision concerning the antithrombotic treatment was taken (atrial fibrillation patients), or the immunosuppressive treatment was last time changed (autoimmune disease patients). Ordinal regression having the total SDM score as dependent variable was used. RESULTS: A total of 665 questionnaires were filled in within the hospital setting (n = 324; 48.7%) and online (n = 341; 51.3%). The median score for SDM was 34 of 45, but it differed between hospital completion -39/45 and online completion (anonymous) -20/45 (P < .001). Patients with higher education were influenced most by the setting, giving the best marks in hospital and low marks online, while those with lower education gave lower marks in both settings. In ordinal regression with SDM score as dependent variable, hospital completion of the questionnaire (OR = 9.5, 95% confidence interval, 5.69-16), collagen disease diagnosis (OR = 2.4, 95% confidence interval, 1.39-4.14), and immunosuppressive treatment (OR = 2.16, 95% confidence interval, 1.43-3.26) were independent predictors. CONCLUSION: In our study, full anonymity was associated with significantly lower scores for the SDM process. The patients with higher education were most influenced by this condition, while those with the lowest education were the most critical.

Percutaneous closure of a large atrial septal defect in a child with severe dextroscoliosis: A case report.

In this study, we present the case of an 11-year-old child with cachexia, severe dextroscoliosis, pectus carinatum, secondary restrictive pulmonary disease, and an incidental finding of a large ostium secundum atrial septal defect (ASD) that was identified on preoperative assessment for surgical correction of the spinal deformity. Transthoracic and transesophageal echocardiography confirmed significant left-to-right shunting with a pulmonary blood flow to systemic blood flow ratio (Qp/Qs) of 3.18 through a 14 mm defect with good circumferential rims, larger than 5 mm. Despite significant left-to-right shunting, the defect was found prior to the development of pulmonary hypertension or right heart enlargement. The decision to close the atrial septal defect by percutaneous intervention was preferred over surgical closure, due to the restrictive pulmonary physiology and low body mass index (12.6 kg/m2). Percutaneous closure of the ASD was successfully performed under general anesthesia using an Occlutech Figulla Flex II ASD device, with no residual shunt. Surgical correction of the dextroscoliosis was subsequently performed with good results. A comprehensive clinical and echocardiographic evaluation is needed in patients with skeletal abnormalities in order to rule out associated congenital heart defects, which may impose therapeutic challenges.

A novel quantitative method for estimating bone mineral density using B-mode ultrasound and radiofrequency signals-a pilot study on patients with rheumatoid arthritis.

The objective of the present study was to evaluate whether an innovative quantitative ultrasound (QUS) technique, Radiofrequency Echographic Multi Spectromety, which combines B-mode ultrasound and radiofrequency signals, is reliable in typical Romanian patients compared to previous results obtained using dual-energy X-ray absorptiometry (DXA). The study prospectively included previously unscreened post-menopausal females with rheumatoid arthritis (RA) and age-matched healthy controls. Bone mineral density (BMD) measurements were performed with an EchoS machine (Echolight®), which combines B-mode ultrasound and radiofrequency signals. The study included 106 RA patients, with a median disease duration of 3.2 (0.5-22) years and 119 controls. RA patients had a significantly lower body weight, body mass index (BMI) and basal metabolic rate (BMR) than the controls, while the prevalence of obesity and body fat differed insignificantly. RA patients had a significantly lower spine and hip BMD, higher fracture risk and higher prevalence of osteoporosis. Compared to RA patients without osteoporosis, those with osteoporosis were significantly older and had a longer menopause duration, but they had a significantly lower BMI, body fat, BMR and prevalence of obesity. Among the controls and RA patients, the median spine and hip BMD became significantly higher as the BMI increased from underweight to obesity. In conclusion, osteoporosis is prevalent among RA patients, as a part of a complex transformation of body mass composition, involving BMI and fat mass. The novel QUS scanning technique was able to replicate the results of the established DXA measurement of BMD and is potentially suitable for screening wide populations for osteoporosis.

Romanian version of SDM-Q-9 validation in Internal Medicine and Cardiology setting: a multicentric cross-sectional study.

BACKGROUND: Shared decision making (SDM) is becoming more and more important for the patient-physician interaction. There has not been a study in Romania evaluating patients' point of view in the SDM process yet. Therefore, the present study aims to evaluate the psychometric parameters of the translated Romanian version of SDM-Q-9. MATERIAL AND METHODS: A multicentric cross-sectional study was performed comprising eight recruitment centers. The sample consisted of in- and outpatients who referred to Hospital Units for treatment for atrial fibrillation or collagen diseases. Furthermore, patients who were members of Autoimmune Disease Patient Society were able to participate via an online survey. All participants completed the Romanian translated SDM-Q-9. RESULTS: Altogether, 665 questionnaires were filled in within the hospital setting (n = 324; 48.7%) and online (n = 341; 51.3%). The Romanian version had good internal consistency (Cronbach α coefficient of 0.96.) Corrected item correlations were good ranging from 0.64 to 0.89 with low corrected item correlations for item 1 and item 7. PCA found a one-factorial solution (similar with previous reports) but the first item had the lowest loading. CONCLUSION: SDM-Q-9 is a useful tool for evaluation and improvement in health care that was validated in Romania and can be used in clinical setting in this country.

Cardiovascular effects of methotrexate in immune-mediated inflammatory diseases.

The cardiovascular effects of disease-modifying antirheumatic drugs and particularly of methotrexate (MTX) are complex and frequently incorrectly understood, which might lead to the unjustified discontinuation of this treatment. MTX, 'the gold standard' and first line treatment in rheumatoid arthritis, psoriatic arthritis, and other immune-mediated inflammatory diseases, has been proven to decrease inflammation, improve cardiovascular risk factors, and reduce mortality. This is supported by both the mechanism of action, as well as a body of clinical data evidence. MTX's cardiovascular effects, although incompletely understood, are explained by its antiproliferative, immunosuppressive, anti-inflammatory, and antiatherogenic effects. Several clinical trials have shown that MTX is associated with improved endothelial function, slower atherosclerosis progression, decreased risk of major cardiovascular adverse events, and benefits on survival. Given its systemic cardiovascular effects, MTX could be regarded as an important therapeutic agent not only to control disease activity in rheumatic diseases, but also to reduce cardiovascular risk and mortality.

Diagnostic challenges in a patient with calciphylaxia - a case report.

Calciphylaxis is a condition with unclear etiopathogeny with vascular calcifications and thrombotic occlusion that lead to necrotic lesions. It is usually described in patients with end-stage renal disease (ESRD), but also in other conditions. The mortality rate is high, due to sepsis and internal organ failure. We present the case of a patient with multiple comorbidities (ESRD, diabetes, hypertension, Mönckeberg's sclerosis) with problems of differential diagnostic due to the necrotic lesions that mislead initially to systemic lupus erythematosus (SLE) with necrotizing vasculitis.

Stevens-Johnsons syndrome or drug-induced lupus - a clinical dilemma: A case report and review of the literature.

Tumor necrosis factor inhibitors are the first biological agents used in the treatment of rheumatoid arthritis (RA) to have yielded satisfactory results in terms of clinical improvement and radiologic progression, but they are also associated with the possibility of occurrence of a number of autoimmune systemic events [drug-induced lupus (DIL), vasculitis, sarcoidosis] and localized adverse events [uveitis, psoriasis, interstitial lung disease, erythema multiforme including the major form Stevens-Johnson syndrome (SJS)]. During treatment with TNF inhibitors, many patients develop positivity for antinuclear, antihistone and anti-double stranded DNA antibodies, though only a minority of patients will develop clinical manifestations and approximately less than 1% will fulfill the classification criteria for systemic lupus erythematosus. Mucocutaneous manifestations are the most frequent manifestations of DIL following treatment with TNF inhibitors, and can be severe and occasionally difficult to differentiate from erythema multiforme/SJS. Stopping the causative drug (the TNF inhibitor) and general supportive measures are usually sufficient in mild forms, but in moderate to severe forms, systemic glucocorticoids and sometimes immunosuppressive drugs are required. The present report presents the case of a patient with rheumatoid arthritis who developed severe recurrent cutaneous reactions and positive autoantibodies during TNF inhibitor treatment, with difficulties in differential diagnosis and treatment. A review of the literature is also presented.

Quantitative Doppler in musculoskeletal ultrasonography - suboptimal performance of both experienced and in-training sonographers in selection of the highest Doppler signal image from cine-loops.

AIMS: Doppler ultrasonography assessment is mandatory nowadays for the complete description of rheumatic disease activity. Initially it was performed in semi quantitative way but recently the (fully) quantitative assessment is gaining more interest. In quantitative assessment, the ratio between total colorized and total pixels (CTR) is computed for the whole image or just for the region of interest (ROI). The frame with the highest amount of Doppler signal (also called worst case scenario image - WCSI) is usually the only one analyzed. The technique requires a very precise identification of WCSI from a certain number of consecutive frames, captured from the same position of the US probe, (and in most cases this is done manually). Our study examined the ability of both experienced and in-training sonographers to identify WCSI using a computerized analytical system as the gold standard. MATERIALS AND METHODS: The study analyzed 480 frame selections done in two distinct exercises. The WCSI and other 3 images with a 5%, 10% and respectively 20% lower level of CTR compared with WCSI were packed in one selection. All frames emerging from the same video clip were randomly presented to six experienced and six in training sonographers; the request was to select the frame with the highest CTR (WCSI) from each package (twenty packages in total). A similar exercise was performed with CTRs decreasing in steps of 2%. RESULTS: In the first exercise the WCSI was correctly identified in 79.1% cases and in 67% of cases in the 2nd exercise. The interobserver agreement between experienced and in-trainer evaluators for the 1st exercise was 0.78 and 0.4 in the 2nd exercise. CONCLUSION: Using computerized analysis as the gold standard, we demonstrated a large heterogeneity across sonographers regarding their ability to identify the best Doppler image even from a small group of frames.

Determinants of Patient-Physician Discordance in Global Assessment in Psoriatic Arthritis: A Multicenter European Study.

OBJECTIVE: Patient-physician discordance in global assessment of disease activity concerns one-third of patients, but what does it reflect? We aimed to assess patient-physician discordance in psoriatic arthritis (PsA) and patient-reported domains of health (physical and psychological) associated with discordance. METHODS: We analyzed the PsAID (Psoriatic Arthritis Impact of Disease), a cross-sectional, multicenter European study of patients with PsA according to expert opinion. Patient global assessment (PGA) and physician global assessment (PhGA) were rated on a 0-10 numeric rating scale. Discordance was defined as the difference (PGA-PhGA) and as the absolute difference |PGA-PhGA| ≥3 points. Determinants of PGA-PhGA were assessed by a stepwise multivariate linear regression among 12 physical and psychological aspects of impact: pain, skin problems, fatigue, ability to work/leisure, functional incapacity, feeling of discomfort, sleep disturbance, anxiety/fear, coping, embarrassment/shame, social participation, and depressive affects. RESULTS: In 460 patients (mean ± SD age 50.6 ± 12.9 years, 52.2% female, mean ± SD disease duration 9.5 ± 9.5 years, mean ± SD Disease Activity Index for Psoriatic Arthritis score 30.8 ± 32.4, and 40.4% undergoing treatment with biologic agents), the mean ± SD PGA was higher than the mean PhGA, with a mean absolute difference of 1.9 ± 1.8 points. Discordance defined by |PGA-PhGA| ≥3 of 10 concerned 134 patients (29.1%), and 115 patients (85.8% of the patients with discordance) had PGA>PhGA. Higher fatigue (ß = 0.14), lower self-perceived coping (ß = 0.23), and impaired social participation (ß = 0.16) were independently associated with a higher difference (PGA-PhGA). CONCLUSION: Discordance concerned 29.1% of these patient/physician dyads, mainly by PGA>PhGA. Factors associated with discordance were psychological rather than physical domains of health. Discordance was more frequent in patients in remission, indicating more work is needed on the patient perspective regarding disease activity.

Efficacy and safety of tanezumab added on to diclofenac sustained release in patients with knee or hip osteoarthritis: a double-blind, placebo-controlled, parallel-group, multicentre phase III randomised clinical trial.

OBJECTIVES: Tanezumab, a monoclonal antibody, inhibits nerve growth factor and reduces chronic pain. This randomised, double-blind, controlled multicentre study was conducted to evaluate the efficacy and safety of tanezumab added to oral diclofenac sustained release (DSR) in patients with hip or knee osteoarthritis (OA) pain. METHODS: Patients (N=604) with moderate to severe knee or hip OA tolerating stable DSR were randomised and treated with DSR 75 mg twice daily combined with intravenous tanezumab 10, 5 or 2.5 mg or placebo at weeks 0, 8 and 16. Co-primary efficacy endpoints (Western Ontario and McMaster Universities OA Index (WOMAC) Pain and Physical Function subscales and patient's global assessment of OA) were assessed at week 16. RESULTS: All co-primary endpoints were significantly improved for all tanezumab+DSR groups versus placebo+DSR (p≤0.039). The incidence of adverse events of abnormal peripheral sensation was lower than in previous tanezumab trials. No new safety signals emerged. Overall incidence of adverse events was higher with tanezumab+DSR (45.2%-49.7%) than with placebo+DSR (34.9%); serious adverse event rates were similar across treatments (5.3%-7.6%). Osteonecrosis was reported in six of 452 patients with tanezumab+DSR (1.3%), but an external adjudication committee did not confirm osteonecrosis in any patient. CONCLUSIONS: Addition of tanezumab to DSR resulted in significant improvements in pain, function and global assessments in patients with OA. Although no new safety signals were observed, the higher incidence of adverse events in the tanezumab+diclofenac group suggests that combination therapy is unfavourable. Further investigations of tanezumab monotherapy for OA pain treatment are required. CLINICAL TRIAL REGISTRATION NUMBER: NCT00864097.