Rheumatology Current Awareness Newsletter

February 2016

Outreach Your Outreach Librarian can help facilitate evidence-based practise for

all Rheumatology staff, as well as assisting with academic study and research. We can help with literature searching, obtaining journal

articles and books, and setting up individual current awareness alerts.

Literature Searching We provide a literature searching service for any library member. For those embarking on their own research it is advisable to book some

time with one of the librarians for a 1 to 1 session where we can guide you through the process of creating a well-focused literature research and introduce you to the health databases access via NHS Evidence.

Critical Appraisal Training We also offer one-to-one or small group training in literature

searching, accessing electronic journals, and critical appraisal/Statistics. These are essential courses that teach how to

interpret clinical papers.

For more information, email: katie.barnard@uhbristol.nhs.uk

Books Books can be searched for using SWIMS our online catalogue at

www.swims.nhs.uk. Books and journals that are not available on site or electronically may be requested from other locations. Please email

requests to: library@uhbristol.nhs.uk

Contents

1: Tables of Contents from February’s

Rheumatology journals

2: New NICE Guidance

3: Latest relevant Systematic Reviews from

the Cochrane Library

4: New activity in Uptodate

5: NHS Behind the Headlines

6: Quick Exercise

7: Current Awareness database articles

Tables of Contents from Rheumatology journals

The links below will take you to the full Tables of Contents.

If you require full articles please email: library@uhbristol.nhs.uk

Rheumatology February 2016, Volume 55, Issue 2

Annals of Rheumatic Disease February 2016, Volume 75, Issue 2

Arthritis & Rheumatology February 2016, Volume 68, Issue 2

Journal of Rheumatology February 2016, Volume 43, Issue 2

Osteoporosis International January 2016, Volume 27, Issue 1

New NICE Guidance

TA375 Adalimumab, etanercept, infliximab, certolizumab pegol, golimumab, tocilizumab and abatacept for rheumatoid arthritis not previously treated with DMARDs or after conventional DMARDs only have failed

Latest relevant Systematic Reviews from the

Cochrane Library

Discharge planning from hospital

New activity in Uptodate

www.uptodate.com

You will need your NHS Athens username/password (register through http://openathens.nice.org.uk/)

Secukinumab for ankylosing spondylitis (January 2016)

Secukinumab, an anti-interleukin (IL)-17A monoclonal antibody, has been approved for use in the

United States and other countries for ankylosing spondylitis (AS). It was beneficial for patients with

active AS in two phase 3 multicenter trials involving a total of nearly 600 patients with active disease

despite optimal nonsteroidal anti-inflammatory drug therapy, some of whom had also responded

inadequately to disease-modifying antirheumatic drugs, including tumor necrosis factor (TNF)

inhibitors [10]. Patients who received the higher dose of secukinumab were significantly more likely,

compared with those receiving placebo, to achieve an ASAS20 response at week 16 (approximately

60 versus 29 percent). Responses were sustained at week 52. Infections, including candidiasis, were

more common in patients receiving secukinumab. Secukinumab may provide a treatment option for

patients with AS who have an inadequate response to TNF inhibitor therapy. (See "Assessment and

treatment of ankylosing spondylitis in adults", section on 'Secukinumab'.)

Secukinumab, an anti-IL17A antibody, for psoriatic arthritis (August 2015, Modified January

2016)

Secukinumab, an anti-interleukin (IL)-17A antibody, is available for the treatment of psoriasis and

psoriatic arthritis in the United States and other countries. It has been evaluated for psoriatic arthritis

(PsA) using various routes of administration and dosing regimens. In a multicenter randomized trial

of almost 400 patients with active PsA, subcutaneously injected secukinumab was superior to placebo

in achieving significant improvement in joint and skin disease, and in physical function and quality of

life at week 24, with sustained benefit at one year [11]. Another trial of over 600 patients

demonstrated that secukinumab, loaded intravenously and then given subcutaneously, resulted in

similar clinical outcomes and also reduced radiographic progression of PsA [12]. (See "Treatment of

psoriatic arthritis".)

NHS Behind the Headlines

Arthritis drug could also help combat ovarian cancer

Monday Jan 11 2016

"A rheumatoid arthritis drug can kill off ovarian cancer cells in women with the BRCA1

mutation," the Mail Online reports. The drug, auranofin, was found to be effective against

ovarian cancer cells associated with the BRCA1 mutation…

Quick Exercise

Creating a search strategy Scenario: A 64 year old obese male who has tried many ways to lose weight presents with a newspaper article about ‘fat-blazer’ (chitosan). He asks for your advice.

1. What would your PICO format be?

Population/problem

Intervention/indicator

Comparator

Outcome

2. What would your research question be?

Taken from the Centre for Evidence Based Medicine

Find out more about constructing an effective search strategy in one of our Literature searching training sessions.

For more details, email library@uhbristol.nhs.uk.

Upcoming Lunchtime Drop-in Sessions

March (1pm)

Thurs 3rd Literature Searching Fri 11th Understanding articles Mon 14th Statistics Tues 22nd Information resources Weds 30th Literature Searching

February (12pm)

Fri 5th Literature Searching

Mon 8th Understanding articles Tues16th Statistics Wed24th Information resources

The Library and Information Service provides free specialist information skills training for

all UHBristol staff and students.

To book a place, email: library@uhbristol.nhs.uk

If you’re unable to attend we also provide one-to-one or small group sessions. Contact

library@uhbristol.nhs.uk or katie.barnard@uhbristol.nhs.uk to arrange a session.

Current Awareness database articles

If you require full articles please email: library@uhbristol.nhs.uk

Title: Rheumatoid arthritis and the risk of dementia: A systematic review and meta-analysis. Citation: Neurology India, Jan 2016, vol. 64, no. 1, p. 56-61, 0028-3886 (2016 Jan-Feb) Author(s): Ungprasert, Patompong, Wijarnpreecha, Karn, Thongprayoon, Charat Abstract: The association between chronic inflammation and dementia has been identified in several epidemiologic studies. However, the data on rheumatoid arthritis (RA), one of the most common chronic inflammatory disorders, remains unclear. We conducted a systematic review and meta-analysis of cohort, case-control, and cross-sectional studies that compared the risk of dementia in patients with RA versus non-RA controls. Data from each study were combined using random-effect, generic inverse variance method of DerSimonian and Laird to calculate the pooled risk ratio (RR) and 95% confidence interval (CI). Three cohort studies and two cross-sectional studies were identified and included in the meta-analysis. We found a significantly increased risk of dementia among patients with RA, with the pooled risk ratio of 1.61 (95% CI, 1.10-2.37). The statistical heterogeneity was high, with an I2 of 91%. Our study demonstrated a statistically significant increase in the risk of dementia among patients with RA. Full Text: Available from ProQuest in Neurology India

Title: Effect of Marine-Derived n-3 Polyunsaturated Fatty Acids on Major Eicosanoids: A Systematic Review and Meta-Analysis from 18 Randomized Controlled Trials. Citation: PloS one, Jan 2016, vol. 11, no. 1, p. e0147351. (2016) Author(s): Jiang, Jiajing, Li, Kelei, Wang, Fenglei, Yang, Bo, Fu, Yuanqing, Zheng, Jusheng, Li, Duo Abstract: Marine-derived n-3 polyunsaturated fatty acids (PUFA) may have a beneficial effect on inflammation via lowering pro-inflammatory eicosanoid concentrations. We aimed to assess the effect of marine-derived n-3 PUFA on prostaglandin E2 (PGE2), thromboxane B2 (TXB2), and leukotriene B4 (LTB4) through systematic review and meta-analysis of randomized controlled trials. A structured search strategy on PubMed, Web of Science and Cochrane up to November 2015 was undertaken in this meta-analysis. Standard mean difference was used to calculate the effect size of marine-derived n-3 PUFA on PGE2, TXB2 and LTB4 in a random-effect model. A total of 18 RCTs with 826 subjects were included in this systematic review and meta-analysis. Supplementation of marine-derived n-3 PUFA significantly decreased concentrations of TXB2 in serum/plasma in subjects with high risk of cardiovascular diseases (SMD:-1.26; 95% CI: -1.65, -0.86) and LTB4 in neutrophils in unhealthy subjects (subjects with non-autoimmune chronic diseases or auto-immune diseases) (SMD:-0.59: 95% CI: -1.02, -0.16). Subgroup analyses showed a significant reduction of LTB4 in subjects with rheumatoid arthritis (SMD: -0.83; 95% CI: -1.37, -0.29), but not in non-autoimmune chronic disease patients (SMD: -0.33; 95% CI: -0.97, 0.31). No significant publication bias was shown in the meta-analysis. Marine-derived n-3 PUFA had a beneficial effect on reducing the concentration of TXB2 in blood of subjects with high risk of CVD as well as LTB4 in neutrophils in unhealthy

subjects, and that subjects with RA showed lower LTB4 content with supplementation of marine-derived n-3 PUFA. Full Text: Available from ProQuest in PLoS One

Title: Surgery for Jaccoud Arthropathy: A Systematic Review. Citation: Journal of clinical rheumatology : practical reports on rheumatic & musculoskeletal diseases, Jan 2016, vol. 22, no. 1, p. 35-38 (January 2016) Author(s): Santos, Willer D, Baleeiro, Carla, Santiago, Mittermayer Barreto Abstract: Jaccoud arthropathy (JA) is characterized by the presence of joint deformities similar to those seen in rheumatoid arthritis but generally with a "reversible" pattern. The etiopathogenic mechanisms are not known, and its therapeutical approach has been regarded as disappointing. The aim of the present study was to perform a systematic review of the literature on the scientific evidence of the surgical procedures for JA. The MEDLINE, LILACS, and Scielo databases were searched using the following keywords: "systemic lupus erythematosus," "rheumatic fever," "Jaccoud arthropathy," "deforming arthropathy," "surgery," and their corresponding terms in Portuguese and Spanish. The search period was between 1966 and 2014. Only 7 articles fulfilled the inclusion criteria, and a total of 58 patients underwent surgical procedures for JA. Such studies were limited to small case series, there was no uniform definition of the outcome, and the follow-up time varied largely. There is no consensus on the best approach for the surgical procedures in patients with JA, who are the best candidates to undergo this, and when to indicate the procedure.

Title: Risk of ischemic stroke in patients with systemic sclerosis: A systematic review and meta-analysis. Citation: Modern rheumatology / the Japan Rheumatism Association, Jan 2016, vol. 26, no. 1, p. 128-131 (January 2016) Author(s): Ungprasert, Patompong, Sanguankeo, Anawin, Upala, Sikarin Abstract: Several chronic inflammatory disorders, such as rheumatoid arthritis and idiopathic inflammatory myositis, have been shown to increase risk of ischemic stroke but the data on systemic sclerosis (SSc) remains unclear. We conducted a systematic review and meta-analysis of observational studies that reported odds ratio, relative risk, hazard ratio, or standardized incidence ratio comparing risk of ischemic stroke in patients with SSc versus non-SSc participants. Pooled risk ratio and 95% confidence intervals (CIs) were calculated using a random-effect, generic inverse variance method of DerSimonian and Laird. Four retrospective cohort studies were identified and included in our data analysis. We found a statistically significant elevated ischemic stroke risk in patients with SSc with a pooled risk ratio of 1.68 (95% CI, 1.26-2.24). The statistical heterogeneity was moderate with an I(2) of 69%. Our study demonstrated a statistically significant increased ischemic stroke risk among patients with SSc.

Title: Prevalence of Peri-implantitis in Medically Compromised Patients and Smokers: A Systematic Review.

Citation: The International journal of oral & maxillofacial implants, Jan 2016, vol. 31, no. 1, p. 111-118 (2016 Jan-Feb) Author(s): Turri, Alberto, Rossetti, Paulo Henrique Orlato, Canullo, Luigi, Grusovin, Maria Gabriella, Dahlin, Christer Abstract: To verify whether the diversity of systemic medical conditions and smoking act as biologic associated factors for peri-implantitis. The PICO question was: "In patients with osseointegrated dental implants, does the presence of smoking habits or a compromised medical status influence the occurrence of peri-implantitis compared with the presence of good general health?" Smoking and systemic conditions such as type 2 diabetes mellitus, cardiovascular diseases, rheumatoid arthritis, lung diseases, obesity, cancer, deep depression, and osteoporosis were screened. Selection criteria included at least 10 patients per condition, 1 year of follow-up after implant loading, and strict cutoff levels (probing pocket depth [PPD], bleeding on probing [BOP] and/or pus, marginal bone loss) to define peri-implantitis. From the 1,136 records initially retrieved, 57 were selected after title and abstract analyses. However, only six papers were considered for qualitative evaluation. No randomized controlled clinical trial was found. Smoking was associated with peri-implantitis in only one out of four studies. Poorly controlled type 2 diabetes accentuated only PPD and radiographic marginal bone level prevalence rates in peri-implant patients (one study). Cardiovascular disease was considered a risk (one out of two studies). The chance of peri-implant patients harboring the Epstein-Barr virus was threefold in one report. No associations were found for rheumatoid arthritis. Data from existing studies point to smoking and diabetes as biologic associated factors for peri-implantitis. However, the body of evidence is still immature, and the specific contribution of general health problems to peri-implantitis requires additional robust epidemiologic and clinical investigations.

Title: Effect of Milnacipran on Pain in Patients with Rheumatoid Arthritis with Widespread Pain: A Randomized Blinded Crossover Trial. Citation: The Journal of rheumatology, Jan 2016, vol. 43, no. 1, p. 38-45, 0315-162X (January 2016) Author(s): Lee, Yvonne C, Massarotti, Elena, Edwards, Robert R, Lu, Bing, Liu, ChihChin, Lo, Yuanyu, Wohlfahrt, Alyssa, Kim, Nancy D, Clauw, Daniel J, Solomon, Daniel H Abstract: Clinical trials have shown that serotonin norepinephrine reuptake inhibitors, such as milnacipran, decrease pain in noninflammatory pain conditions such as fibromyalgia and osteoarthritis. We examined the effect of milnacipran on self-reported pain intensity and experimental pain sensitivity among patients with rheumatoid arthritis (RA) with widespread pain and stable RA disease activity. In this double-blind, crossover study, patients with RA with widespread pain, receiving a stable treatment regimen, were randomized (by a random number generator) to receive milnacipran 50 mg twice daily or placebo for 6 weeks, followed by a 3-week washout and crossed over to the other arm for the remaining 6 weeks. The primary outcome was change in average pain intensity, assessed by the Brief Pain Inventory short form. The sample size was calculated to detect a 30% improvement in pain with power = 0.80 and α = 0.05. Of the 43 randomized subjects, 41 received the study drug, and 32 completed the 15-week study per protocol. On a 0-10 scale, average pain intensity decreased by 0.39 (95% CI -1.27 to 0.49, p = 0.37) more points during 6 weeks of milnacipran treatment compared with placebo. In the subgroup of subjects with swollen joint count ≤ 1, average pain intensity decreased by 1.14 more points during 6 weeks of milnacipran compared with placebo (95% CI -2.26 to -0.01, p = 0.04). Common adverse events

included nausea (26.8%) and loss of appetite (9.7%). Compared with placebo, milnacipran did not improve overall, self-reported pain intensity among subjects with widespread pain receiving stable RA medications. ClinicalTrials.gov NCT01207453.

Title: Alterations in immune function with biologic therapies for autoimmune disease. Citation: The Journal of allergy and clinical immunology, Jan 2016, vol. 137, no. 1, p. 19-27 (January 2016) Author(s): Her, Minyoung, Kavanaugh, Arthur Abstract: Autoimmune disorders, including rheumatoid arthritis, inflammatory bowel disease, psoriasis, and others, are characterized by dysregulation of various aspects of normal immunity and inflammation. Biologic agents targeting key components of the dysregulated immune response have dramatically improved patient outcomes and transformed treatment paradigms for a number of systemic inflammatory autoimmune diseases. Despite their excellent efficacy, because they do affect normal immune responsiveness, biologic agents can potentially be associated with a variety of adverse effects. Important potential adverse effects related to the use of biologic agents include immunosuppression, which might result in outcomes such as infection, and autoimmunity, that could result in paradoxical inflammation or even autoimmune disease. In this article the current clinical evidence and immunologic mechanisms of the adverse effects related to biologic agents are discussed. Published by Elsevier Inc.

Title: A Comparison of Biological Activity of B Lymphocyte Stimulator (BLyS) Antagonist Peptibodies and the Elucidation of Possible BLyS Binding Sites. Citation: Protein and peptide letters, Jan 2016, vol. 23, no. 1, p. 17-23 (2016) Author(s): Hao, Xiafei, Zhu, Yanfeng, Zheng, Chang, Fu, Xuegang, Feng, Jiannan, Shen, Beifen, Wei, Jing Abstract: B lymphocyte stimulator (BLyS) overexpression is associated with autoimmune diseases such as rheumatoid arthritis and lupus. BLyS antagonists are new effective therapeutic strategies that have been studied extensively. BLyS-binding peptides, BC originated from computer-aided drug design (CADD), 814 selected from the phage display library, as well as the 3-copy of BC (3-BC), were fused with human IgG1 Fc to constitute peptide-Fc fusion proteins, referred as peptibodies. BP-Fc, a peptibody possessing the identical sequence as BC-Fc but a His tag, was also constructed. The biological activities of these peptibodies were assessed by Enzyme-Linked Immuno Sorbent Assay (ELISA). Furthermore, the potential interacting orientations of BP and 814 with BLyS were studied. At 100 μg/ml, BC-Fc, BP-Fc, 814-Fc and 3-BC-Fc could distinctly inhibit 64 %, 50 %, 73 % and 56 % of the interaction of B cell maturation antigen (BCMA) with BLyS respectively. BP-Fc demonstrated 15 % higher binding ratio with BLyS than BC-Fc at 100 μg/ml. However, 814-Fc displayed at least 39 % higher BLyS-binding activity than BP-Fc at different concentrations. The binding capacity of 3-BC-Fc was slightly superior to BC-Fc. In addition, 814 and BP shared the identical domain on the surface of BLyS which involves in binding with BCMA, but owned the detached orientations. The discovery of possible locations of the BLyS-targeted peptides lays the foundation for the development of novel antagonists. Both BP-Fc and 3-BC-Fc fusion proteins could bind to BLyS in a dose-dependent manner and inhibit BLyS biological activity significantly, which might act as candidate agents for autoimmune disease therapy.

Title: Agreements and Discrepancies between FDA Reports and Journal Papers on Biologic Agents Approved for Rheumatoid Arthritis: A Meta-Research Project. Citation: PloS one, Jan 2016, vol. 11, no. 1, p. e0147556. (2016) Author(s): Amarilyo, Gil, Furst, Daniel E, Woo, Jennifer M P, Li, Wen, Bliddal, Henning, Christensen, Robin, Tarp, Simon Abstract: Sponsors that seek to commercialize new drugs apply to the Food and Drug Administration (FDA) which independently analyzes the raw data and reports the results on its website. This study sought to determine if there are differences between the FDA assessments and journal reports on biologic agents developed for the treatment of rheumatoid arthritis. Available data on FDA-approved drugs were extracted from the website, and a systematic literature search was conducted to identify matching studies in peer-reviewed medical journals. Outcome measures were the American College of Rheumatology response criteria ACR20 (efficacy) and withdrawal due to adverse events (safety). As effect size odds ratios were estimated for each active trial arm vs. control arm (i.e. for both sources: FDA and journal report), followed by calculation of the ratios of the FDA and journal report odds ratios. A ratio of odds ratios not equal to 1 was categorized as a discrepancy. FDA reports were available for 8 of 9 FDA-approved biologic agents for rheumatoid arthritis; all identified trials (34) except one were published in peer-reviewed journals. Overall, discrepancies were noted for 20 of the 33 evaluated trials. Differences in the apparent benefit reporting were found in 39% (24/61) pairwise comparisons and in 11 cases these were statistically significant; the FDA report showed greater benefit than the journal publication in 15 comparisons and lesser benefit in 9. Differences in the reported harms were found in 51% (28/55) pairwise comparisons and were statistically significant in 5. The "signal" in FDA reports showed a less harmful effect than the journal publication in 17 comparisons whereas a more harmful effect in 11. The differences were attributed to differences in analytic approach, patient inclusion, rounding effect, and counting discrepancies. However, no differences were categorized as critical. There was no empirical evidence to suggest biased estimates between the two sources. Increased and detailed transparency in publications would improve the understanding and credibility of published results. Further, the FDA report was found to be a useful source when data are missing in the published report (i.e. reporting bias). Full Text: Available from ProQuest in PLoS One

Title: Does disease activity add to functional disability in estimation of utility for rheumatoid arthritis patients on biologic treatment? Citation: Rheumatology (Oxford, England), Jan 2016, vol. 55, no. 1, p. 94-102 (January 2016) Author(s): Nair, Sandhya C, Welsing, Paco M J, Marijnissen, Anne Karien C A, Sijtsma, Paulina, Bijlsma, Johannes W J, van Laar, Jacob M, Lafeber, Floris P J G, de Wit, G Ardine Abstract: Treatment in general is mostly directly aimed at disease activity, and measures such as the DAS28 might therefore present important additional information. Our aim was to develop and validate a model that uses a combination of disease activity (DAS28) and HAQs to estimate EuroQoL 5-dimension scale (EQ5D) utilities. Longitudinal data from a cohort study in RA patients from the Utrecht Rheumatoid Arthritis Cohort study Group (Stichting Reumaonderzoek Utrecht) who started treatment with a biologic drug were used for mapping and validation. All 702 observations, including

DAS28, HAQ and EQ5D assessed at the same time points, were used. The observations were randomly divided into a subset for development of the model (n = 428 observations) and a subset for validation (n = 274). A stepwise multivariable regression analysis was used to test the association of DAS28 (components) and HAQ (domains) with EQ5D. Model performance was assessed using the explained variance (R(2)) and root mean square errors. Observed and predicted utility scores were compared to check for under- or overestimation of the scores. Finally, the performance of the model was compared with published mapping models. Lower DAS28 score and HAQ items dressing and grooming, arising, eating, walking and activities were associated with higher EQ5D scores. The final model had an explained variance of 0.35 and a lower root mean square error as compared with other models tested. The agreement between predicted and observed scores was fair. HAQ components estimate EQ5D better than total HAQ. Adding DAS28 to HAQ components does not result in better utility estimations. © The Author 2015.

Title: Treatment persistence among patients with rheumatoid disease (RA, AS, PsA) treated with subcutaneous biologics in Germany. Citation: Rheumatology international, Jan 2016, vol. 36, no. 1, p. 143-153 (January 2016) Author(s): Lyu, Ramon, Govoni, Marinella, Ding, Qian, Black, Christopher M, Kachroo, Sumesh, Fan, Tao, Ogbonnaya, Augstina, Donga, Prina, Hill, Jerrold, Makin, Charles Abstract: Patients with rheumatoid arthritis (RA), ankylosing spondylitis (AS), and psoriatic arthritis (PsA) are frequently treated with subcutaneous biologic therapies when disease progresses or when response to synthetic disease-modifying antirheumatic drugs (DMARDs) is inadequate. This study analyzed treatment persistence and treatment patterns for RA, AS, and PsA patients in Germany initiating subcutaneous biologic therapies with and without prior DMARDs use. A retrospective cohort study was conducted using the Electronic Medical Record database of IMS Disease Analyzer, Germany. Patients who were ≥18 years old; had at least one ICD-10 diagnosis code of RA, AS, or PsA during the study period; and had exposure to a subcutaneous biologic agent between January 1, 2009 and June 30, 2012 were selected. Patients were required to have continuous observation ≥12 months prior to and after index medication date. Persistence was defined as consecutive days from treatment initiation until treatment discontinuation (≥60-day lapse in medication coverage). Patients were stratified by pre-index use of DMARDs. Kaplan-Meier analysis was conducted to assess time to discontinuation, and logistic regression was conducted to identify characteristics associated with persistence. A total of 576 RA, 108 AS, and 197 PsA patients without biologic experience during the pre-index period were selected. The percentages of RA, AS, and PsA patients persistent ≥12 months were 51.9, 48.1, and 57.9 %, respectively. Median persistent time over 12 months was 365.0 days for RA (mean 245.9 days), 281.0 for AS (mean 228.5), and 365.0 for PsA (mean 264.1). In the RA cohort, a significantly higher proportion of those with pre-index DMARD use were persistent compared to those without pre-index DMARD (56.1 vs. 33.3 %, p = 0.0001). No significant differences were observed for the AS and PsA cohorts. Multivariate analyses confirmed that DMARD-experienced patients were 2.45 times more likely to be persistent with subcutaneous biologic therapy in the RA cohort. Switching between subcutaneous biologics occurred in <10 % of patients in all three cohorts. In the subpopulations with at least two prescriptions for the index subcutaneous biologic and who remained persistent on the index subcutaneous biologic, dose escalation of ≥50 % occurred in 50, 60, and 49 % in the RA, AS, and PsA cohorts, respectively. Among RA, AS, and PsA patients newly initiating subcutaneous biologic agents in Germany, persistence at 12 months is relatively low (48-58 %). For the RA cohort, patients with pre-index DMARD use are more persistent than patients without. The majority of patients do not switch between subcutaneous biologics. A notable proportion of patients who remained persistent on their index subcutaneous biologic had a dose

escalation. There are opportunities to improve outcomes of patient with rheumatoid disease through improved medication persistence.

Title: Fatigue in Primary Sjögren's Syndrome: Clinical, Laboratory, Psychometric, and Biologic Associations. Citation: Arthritis care & research, Jan 2016, vol. 68, no. 1, p. 123-131 (January 2016) Author(s): Karageorgas, Theofanis, Fragioudaki, Sofia, Nezos, Adrianos, Karaiskos, Dimitrios, Moutsopoulos, Haralampos M, Mavragani, Clio P Abstract: To identify independent contributors of fatigue in primary Sjögren's syndrome (SS) patients, taking into account clinical, laboratory, and psychological features, and to explore the potential role of interferon (IFN)-induced gene indoleamine 2,3-dioxygenase (IDO-1), anti-21-hydroxylase (anti-21[OH]) antibodies, and soluble BAFF. Detailed clinical and laboratory characteristics were recorded for 106 primary SS patients. The Functional Assessment of Chronic Illness Therapy-Fatigue, Zung Depression Scale, State-Trait Anxiety Inventory, Eysenck Personality Questionnaire Scale, and Athens Insomnia Scale were adopted to assess fatigue, depression, anxiety, and sleep disturbances, respectively. Peripheral whole blood expression levels of IDO-1, as well as type I and II IFN-induced genes were calculated using quantitative reverse transcriptase-polymerase chain reaction. Serum anti-21(OH) antibodies and soluble BAFF levels were determined by a radioimmunoassay and an enzyme-linked immunosorbent assay, respectively. Univariate and multivariate models were performed to identify determinants of fatigue. Fatigue was detected in 32 of 106 (30.2%) primary SS patients. In univariate analysis, fatigue was associated with arthralgias/myalgias, fibromyalgia hydroxychloroquine therapy, both state and trait anxiety scores, depression, and neuroticism, as well as impaired sleep patterns. Multivariate analysis revealed neuroticism (odds ratio [OR] 6.9, [95% confidence interval (95% CI) 1.7-28.0]), depression (OR 3.0 [95% CI 0.8-11.0]), and fibromyalgia (OR 5.5 [95% CI 1.1-27.7]) as independent fatigue contributors. Soluble BAFF levels, anti-21(OH) autoantibodies, and IDO-1 messenger RNA expression did not significantly differ between fatigued and nonfatigued primary SS patients. Depression, neuroticism, and fibromyalgia play a major role in primary SS-associated fatigue and should be addressed in clinical practice, with active collaboration between rheumatologists and mental health professionals. Further studies are warranted in order to explore underlying pathophysiologic pathways that might explain fatigue in the setting of primary SS. © 2016, American College of Rheumatology.

Title: Comparative Risk of Hospitalized Infection Associated With Biologic Agents in Rheumatoid Arthritis Patients Enrolled in Medicare. Citation: Arthritis & rheumatology (Hoboken, N.J.), Jan 2016, vol. 68, no. 1, p. 56-66 (January 2016) Author(s): Yun, Huifeng, Xie, Fenglong, Delzell, Elizabeth, Levitan, Emily B, Chen, Lang, Lewis, James D, Saag, Kenneth G, Beukelman, Timothy, Winthrop, Kevin L, Baddley, John W, Curtis, Jeffrey R Abstract: The risks of hospitalized infection associated with biologic agents used to treat rheumatoid arthritis (RA) are unclear. The aim of this study was to determine whether the associated risk of hospitalized infections differed between specific biologic agents used to treat RA. In a retrospective cohort study using Medicare data from 2006-2011 for all enrolled patients with RA, new episodes of treatment with etanercept, adalimumab, certolizumab, golimumab, infliximab, abatacept, rituximab, and tocilizumab were identified. Patients were required to have received another biologic agent

previously and to have been continuously enrolled in Medicare medical and pharmacy plans during the baseline period and throughout followup. Followup started on the date of initiation of treatment with the new biologic agent (after previous treatment with a different biologic agent) and ended on the date of the earliest hospitalized infection, at 12 months, after an exposure gap of >30 days, or at the time of death or loss of Medicare coverage. Cox regression analysis was used to calculate the adjusted hazard ratio (HR) for hospitalized infection, adjusting for an infection risk score and other confounders. Of 31,801 new biologic treatment episodes in patients who had previously received another biologic agent, 12.0% were with etanercept, 15.2% with adalimumab, 5.9% with certolizumab, 4.4% with golimumab, 12.4% with infliximab, 28.9% with abatacept, 14.8% with rituximab, and 6.3% with tocilizumab. During followup, we identified 2,530 hospitalized infections; incidence rates ranged from 13.1 per 100 person-years (abatacept) to 18.7 per 100 person-years (rituximab). After adjustment, etanercept (HR 1.24, 95% confidence interval [95% CI] 1.07-1.45), infliximab (HR 1.39, 95% CI 1.21-1.60), and rituximab (HR 1.36, 95% CI 1.21-1.53) had significantly higher HRs for hospitalized infection compared with abatacept. In RA patients with prior exposure to a biologic agent, exposure to etanercept, infliximab, or rituximab was associated with a greater 1-year risk of hospitalized infection compared with the risk associated with exposure to abatacept. © 2016, American College of Rheumatology.

Title: Effectiveness of Nonpharmacologic Interventions for Decreasing Fatigue in Adults With Systemic Lupus Erythematosus: A Systematic Review. Citation: Arthritis care & research, Jan 2016, vol. 68, no. 1, p. 141-148 (January 2016) Author(s): Del Pino-Sedeño, Tasmania, Trujillo-Martín, María M, Ruiz-Irastorza, Guillermo, Cuellar-Pompa, Leticia, de Pascual-Medina, Ana M, Serrano-Aguilar, Pedro, Spanish Systemic Lupus Erythematosus CPG Development Group Abstract: Survival of patients with systemic lupus erythematosus (SLE) has significantly improved over the past decades. As SLE patients live longer they inevitably experience a range of clinical manifestations and somatic symptoms. Quality of life may also be impacted through a range of subjective indicators. Among these parameters, fatigue is the most prevalent complaint. Nonpharmacologic strategies seem regularly utilized for fatigue management in SLE; however, their real effects are not known. A systematic review was conducted to analyze the effectiveness of nonpharmacologic interventions to reduce fatigue in SLE patients. Medline/PreMedline, Embase, PsycINFO, SCI-EXPANDED, Social Sciences Citation Index, and the Cochrane Library were searched (June 2014). Studies were included and assessed for quality if they fulfilled prespecified criteria. A total of 12 studies were finally included (n = 549): 7 randomized trials, 1 nonrandomized trial, and 4 prospective observational studies. They assessed 5 main intervention categories: exercise, behavioral and psychological approaches, diets, acupuncture, and phototherapy. All interventions produced reductions in fatigue, as measured using at least 1 instrument. Aerobic exercise was found to be effective and suitable for reducing fatigue, but results were not always consistent across instruments used. The diversity of psychological interventions limits the significance of the results; however, data point to a positive impact on fatigue. There are still few data on the effect of acupuncture, diets, and ultraviolet A radiation. Studies are few and heterogeneous; however, nonpharmacologic interventions applied to SLE patients can be effective in reducing fatigue. © 2016, American College of Rheumatology.

Title: Relapse rates in patients with rheumatoid arthritis in stable remission tapering or stopping antirheumatic therapy: interim results from the prospective randomised controlled RETRO study.

Citation: Annals of the rheumatic diseases, Jan 2016, vol. 75, no. 1, p. 45-51 (January 2016) Author(s): Haschka, Judith, Englbrecht, Matthias, Hueber, Axel J, Manger, Bernhard, Kleyer, Arnd, Reiser, Michaela, Finzel, Stephanie, Tony, Hans-Peter, Kleinert, Stefan, Feuchtenberger, Martin, Fleck, Martin, Manger, Karin, Ochs, Wolfgang, Schmitt-Haendle, Matthias, Wendler, Joerg, Schuch, Florian, Ronneberger, Monika, Lorenz, Hanns-Martin, Nuesslein, Hubert, Alten, Rieke, Demary, Winfried, Henes, Joerg, Schett, Georg, Rech, Juergen Abstract: To prospectively analyse the risk for disease relapses in patients with rheumatoid arthritis (RA) in sustained remission, either continuing, tapering or stopping disease-modifying antirheumatic drugs (DMARDs) in a prospective randomised controlled trial. Reduction of Therapy in patients with Rheumatoid arthritis in Ongoing remission is a multicentre, randomised controlled, parallel-group phase 3 trial evaluating the effects of tapering and stopping all conventional and/or biological DMARDs in patients with RA in stable remission. Patients (disease activity score 28 (DAS28)<2.6 for least 6 months) were randomised into three arms, either continuing DMARDs (arm 1), tapering DMARDs by 50% (arm 2) or stopping DMARDs after 6 months tapering (arm 3). The primary endpoint was sustained remission during 12 months. In this interim analysis, the first 101 patients who completed the study were analysed. At baseline, all patients fulfilled DAS28 remission and 70% also American College of Rheumatology- European League Against Rheumatism Boolean remission. 82.2% of the patients received methotrexate, 40.6% biological DMARDs and 9.9% other DMARDs. Overall, 67 patients (66.3%) remained in remission for 12 months, whereas 34 patients (33.7%) relapsed. The incidence of relapses was related to study arms (p=0.007; arm 1: 15.8%; arm 2: 38.9%; arm 3: 51.9%). Multivariate logistic regression identified anticitrullinated protein antibodies (ACPA) positivity (p=0.038) and treatment reduction (in comparison to continuation) as predictors for relapse (arm 2: p=0.012; arm 3: p=0.003). This randomised controlled study testing three different treatment strategies in patients with RA in sustained remission demonstrated that more than half of the patients maintain in remission after tapering or stopping conventional and biological DMARD treatment. Relapses occurred particularly in the first 6 months after treatment reduction and were associated with the presence of ACPA. 2009-015740-42. Full Text: Available from Highwire Press in Annals of the Rheumatic Diseases

Title: Biological activity of a small molecule indole analog, 1-[(1H-indol-3-yl)methylene]-2-phenylhydrazine (HMPH), in chronic inflammation. Citation: Chemico-biological interactions, Jan 2016, vol. 244, p. 71-83 (January 25, 2016) Author(s): Misra, Chandra Sekhar, Gejjalagere Honnappa, Chethan, Jitta, Srinivas Reddy, Gourishetti, Karthik, Daram, Prasanthi, Singh, Mahendra Pal, Hosur Shrungeswara, Akhila, Nayak, Yogendra, Unnikrishnan, Mazhuvancherry Kesavan Abstract: A synthetic small molecule, 1-[(1H-indol-3-yl)methylene]-2-phenylhydrazine (HMPH) was conveniently synthesised by a one-step reaction, purified and characterised by chromatographic and spectroscopic methods. HMPH scavenged free radicals and inhibited lipopolysaccharide (LPS)-induced ROS generation and NO release in RAW-264.7 cells without signs of any detectable cytotoxicity. HMPH inhibited lipid peroxidation (LPO) with IC50 of 135 ± 9 as against 58 ± 8 μM for α-tocopherol. Further, HMPH (>50 μM) significantly reduced the LPS-induced TNF-α release in mouse peritoneal macrophages and in human peripheral blood mononuclear cells (PBMCs). HMPH did not show any visible signs of toxicity in rats up to 400 mg/kg/intraperitoneal and 2000 mg/kg/oral.

HMPH at 25 and 50 mg/kg attenuated neutrophil infiltration in air-pouch lavage and bronchoalveolar lavage (BAL) in rat models. HMPH also reduced myeloperoxidase (MPO), nitrite and TNF-α in air-pouch lavage in addition to MPO in plasma. HMPH reduced acute paw-inflammation in carrageenan-induced paw-edema. HMPH consistently decreased both ipsilateral and contralateral paw inflammation, minimised the clinical scores of arthritis, prevented body weight (B.wt.) loss, attenuated serum C-reactive protein (C-RP) and rheumatoid factors (RF) in rat model of adjuvant-induced arthritis. Histopathology and radio-graphical reports show that HMPH reduced bone erosion in both ipsilateral and contralateral paw joints. Failure to inhibit COX suggests that effectiveness of HMPH in both acute and chronic inflammation is mediated by a multimodal mechanism involving modulation of immunity, attenuating TNF-α, protecting bone attrition and reducing oxidative stress. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Title: Effects of Person-Centered Physical Therapy on Fatigue-Related Variables in Persons With Rheumatoid Arthritis: A Randomized Controlled Trial. Citation: Archives of physical medicine and rehabilitation, Jan 2016, vol. 97, no. 1, p. 26-36 (January 2016) Author(s): Feldthusen, Caroline, Dean, Elizabeth, Forsblad-d'Elia, Helena, Mannerkorpi, Kaisa Abstract: To examine effects of person-centered physical therapy on fatigue and related variables in persons with rheumatoid arthritis (RA). Randomized controlled trial. Hospital outpatient rheumatology clinic. Persons with RA aged 20 to 65 years (N=70): intervention group (n=36) and reference group (n=34). The 12-week intervention, with 6-month follow-up, focused on partnership between participant and physical therapist and tailored health-enhancing physical activity and balancing life activities. The reference group continued with regular activities; both groups received usual health care. Primary outcome was general fatigue (visual analog scale). Secondary outcomes included multidimensional fatigue (Bristol Rheumatoid Arthritis Fatigue Multi-Dimensional Questionnaire) and fatigue-related variables (ie, disease, health, function). At posttest, general fatigue improved more in the intervention group than the reference group (P=.042). Improvement in median general fatigue reached minimal clinically important differences between and within groups at posttest and follow-up. Improvement was also observed for anxiety (P=.0099), and trends toward improvements were observed for most multidimensional aspects of fatigue (P=.023-.048), leg strength/endurance (P=.024), and physical activity (P=.023). Compared with the reference group at follow-up, the intervention group improvement was observed for leg strength/endurance (P=.001), and the trends toward improvements persisted for physical (P=.041) and living-related (P=.031) aspects of fatigue, physical activity (P=.019), anxiety (P=.015), self-rated health (P=.010), and self-efficacy (P=.046). Person-centered physical therapy focused on health-enhancing physical activity and balancing life activities showed significant benefits on fatigue in persons with RA.

Title: Step-down strategy of spacing TNF-blocker injections for established rheumatoid arthritis in remission: results of the multicentre non-inferiority randomised open-label controlled trial (STRASS: Spacing of TNF-blocker injections in Rheumatoid ArthritiS Study). Citation: Annals of the rheumatic diseases, Jan 2016, vol. 75, no. 1, p. 59-67 (January 2016) Author(s): Fautrel, Bruno, Pham, Thao, Alfaiate, Toni, Gandjbakhch, Frédérique, Foltz, Violaine, Morel, Jacques, Dernis, Emmanuelle, Gaudin, Philippe, Brocq, Olivier, Solau-Gervais, Elisabeth, Berthelot, Jean-Marie, Balblanc, Jean-Charles, Mariette, Xavier, Tubach, Florence

Abstract: Tumour necrosis factor (TNF)-blocker tapering has been proposed for patients with rheumatoid arthritis (RA) in remission. The trial aims to compare the effect of progressive spacing of TNF-blocker injections (S-arm) to their maintenance (M-arm) for established patients with RA in remission. The study was an 18-month equivalence trial which included patients receiving etanercept or adalimumab at stable dose for ≥1 year, patients in remission on 28-joint Disease Activity Score (DAS28) for ≥6 months and patients with stable joint damage. Patients were randomised into two arms: maintenance or injections spacing by 50% every 3 months up to complete stop. Spacing was reversed to the previous interval in case of relapse, and eventually reattempted after remission was reachieved. The primary outcome was the standardised difference of DAS28 slopes, based on a linear mixed-effects model (equivalence interval set at ±30%). 64 and 73 patients were included in the S-arm and M-arm, respectively, which was less than planned. In the S-arm, TNF blockers were stopped for 39.1%, only tapered for 35.9% and maintained full dose for 20.3%. The equivalence was not demonstrated with a standardised difference of 19% (95% CI -5% to 46%). Relapse was more common in the S-arm (76.6% vs 46.5%, p=0.0004). However, there was no difference in structural damage progression. Tapering was not equivalent to maintenance strategy, resulting in more relapses without impacting structural damage progression. Further studies are needed to identify patients who could benefit from such a strategy associated with substantial cost savings. ClinicalTrials.gov: NCT00780793; EudraCT identifier: 2007-004483-41. Full Text: Available from Highwire Press in Annals of the Rheumatic Diseases

Title: Neuropsychiatric manifestations of Sydenham's chorea: a systematic review. Citation: Developmental medicine and child neurology, Jan 2016, vol. 58, no. 1, p. 16-28 (January 2016) Author(s): Punukollu, Mallika, Mushet, Nadine, Linney, Marisa, Hennessy, Colm, Morton, Michael Abstract: Sydenham's chorea is a post-streptococcal, autoimmune, neuropsychiatric movement disorder. Sydenham's chorea is a major criterion for diagnosis of acute rheumatic fever with the implication of potential long-term sequelae including cardiac complications. It is well established that there is psychiatric comorbidity in Sydenham's chorea, but there are variations in the literature regarding the nature and prevalence of psychiatric diagnoses associated with Sydenham's chorea. The aim of this review was to systematically evaluate the evidence for psychiatric symptoms presenting with Sydenham's chorea. Knowledge of comorbid psychiatric symptomatology will support early diagnosis and treatment, leading to improved long-term outcomes for children with Sydenham's chorea. The study used a systematic search strategy, using MEDLINE, MEDLINE in Process, EMBASE, and The Cochrane Library. Abstracts were screened to identify relevant papers which were then assessed further. Eligible papers were summarized. A total of 1429 abstracts of relevant studies were found, and 49 papers reporting neuropsychiatric symptoms in Sydenham's chorea were summarized. Obsessive-compulsive disorder was the most commonly studied, and hence reported, neuropsychiatric symptom in children with Sydenham's chorea. The studies analysed used a variety of tools to identify affected children and used different methods for analysing results. Attention-deficit-hyperactivity disorder, affective disorders, tic disorders, executive function disturbances, and psychotic features were also reported as comorbidities. There is good evidence of neuropsychiatric comorbidities in Sydenham's chorea. In countries with a high prevalence of rheumatic fever, the early recognition of salient cognitive and psychiatric symptoms may aid in the management of Sydenham's chorea. © 2015 Mac Keith Press.

Title: Development of a sensitive enzyme-linked immunosorbent assay for the measurement of biologically active etanercept in patients with ankylosing spondylitis. Citation: Journal of chromatography. B, Analytical technologies in the biomedical and life sciences, Jan 2016, vol. 1008, p. 219-224 (January 1, 2016) Author(s): Wang, Lei, Wang, Xiaoxia, Li, Ying, Cheng, Zeneng Abstract: Etanercept is the first tumor necrosis factor inhibitor to be approved for rheumatic disease treatment. Its in vivo concentration is usually detected with commercial enzyme-linked immunosorbent assay (ELISA) kits; specifically, previous researchers have mostly used double-antibody sandwich ELISA technology. Double-antibody sandwich ELISA is employed to detect the total etanercept rather than biologically active etanercept, which is more relevant in terms of therapeutic drug monitoring. In this work, a sensitive ELISA that employed its antigen TNF-α to capture biologically active etanercept for concentration detection was established and validated for etanercept pharmacokinetic (PK) study in patients with ankylosing spondylitis (AS). The proposed assay was demonstrated to be precise and accurate over the linear range of 12.5-400pg/mL. The intra- and inter-assay relative standard deviation ranged from 3.9 to 12.2% and 6.2 to 11.1%, respectively, and recovery varied between 90.1 and 99.7%, confirming the assay's reliability. The effectiveness and accuracy of the assay was also validated according to quality samples containing etanercept with different TNF-α concentrations, and with plasma samples from patients with AS. To complete the study, both the proposed assay and double-antibody sandwich ELISA were applied to the PK study of etanercept in patients and compared. The multiple-dose results of both analytical methods were consistent, while the drug exposure of the first dose as-detected by the proposed assay was lower than that detected by double-antibody sandwich ELISA. In conclusion, the proposed ELISA was shown to provide more accurate concentration data for therapeutic drug monitoring in comparison to commercial ELISA kits. Copyright © 2015 Elsevier B.V. All rights reserved.

Title: Efficacy and safety of combination therapy for preventing bone damage in rheumatoid arthritis. Citation: Clinical rheumatology, Jan 2016, vol. 35, no. 1, p. 19-23 (January 2016) Author(s): Iannone, Florenzo, Lopalco, Giuseppe, Cantarini, Luca, Galeazzi, Mauro, Lapadula, Giovanni Abstract: The main outcomes of the therapies for rheumatoid arthritis (RA) must be preventing, or at least lessening, the development of structural damage. Biological disease-modifying anti-rheumatic drugs (bDMARDs), targeting tumour necrosis factor-α (TNF-α) or other key steps (IL-1, IL-6, T cells, B cells) in the pathogenesis of RA, have given clues to be effective and safe as treatments for RA, being capable of improving disease activity, ameliorating functional ability and halting joint damage. A large body of evidence, stemming from randomized clinical trials, observational studies, and registries, has shown that the beneficial effects of the bDMARDs become optimal when combined with synthetic (s)-DMARDs, mainly methotrexate (MTX). Despite combination therapy is advocated by the international guidelines for the management of RA, data from the daily standard of care indicate that almost one third of RA patients are treated with bDMARDs as monotherapy. Many reasons may be taken into account to explain this gap from official recommendations, among which the fact that in real-life settings, the assessment of clinical outcomes is exclusively based on clinical indices, disregarding the evolution of bone damage. Furthermore, some bDMARDs have been

launched in the market with the official approval to be used as monotherapy. But even for the latter, there is no conclusive proof that monotherapy regimen is comparable to co-therapy with MTX in preventing articular damage. In conclusion, the most recent published data show that combination therapy with bDMARDs and MTX represents the best therapeutic option for the treatment of RA since it can stop or at least slow the progression of disabling structural damage.

Title: Malignancy risk of anti-tumor necrosis factor alpha blockers: an overview of systematic reviews and meta-analyses. Citation: Clinical rheumatology, Jan 2016, vol. 35, no. 1, p. 1-18 (January 2016) Author(s): Chen, Yuehong, Sun, Jianhong, Yang, Yuan, Huang, Yupeng, Liu, Gang Abstract: The objective of the study is to systematically review the malignancy risk of anti-tumor necrosis factor alpha (anti-TNFα) agents. Databases of PubMed Medline, OVID EMBASE, and Cochrane Library were searched to identify published systematic reviews and meta-analyses of randomized control trials, observational studies, and case series that evaluated malignancy risk of anti-TNFα blockers. Search time duration was restricted from January 1st, 2000 to July 16th, 2015. Overview Quality Assessment Questionnaires were used to assess the quality of included reviews. Two methodology trained reviewers separately and repeatedly screened searched studies according to study selection criteria, collected data, and assessed quality. Totally, 42 reviews proved eligible with only one Cochrane review. Anti-TNFα antagonists were extensively used to treat various diseases; nevertheless, malignancy risks were most commonly described in patients with rheumatoid arthritis (RA) and inflammatory bowel disease (IBD). In RA patients, no increased risks of breast cancer, lymphoma, and non-melanoma skin cancer were found, but if the use of anti-TNFα agents was associated with elevated risk of overall malignancy was still uncertainty. In IBD patients, the use of anti-TNFα inhibitors was not connected with enhanced risk of overall cancer. No increased cancer risk was found in other disease conditions. Twenty-nine reviews were rated as good quality, 12 as moderate, and one as poor. There are no sufficient evidences to draw the conclusion that anti-TNFα blockers have relationship with increased malignancy risk.

Title: Etanercept treatment-related c-ANCA-associated large vessel vasculitis. Citation: Clinical rheumatology, Jan 2016, vol. 35, no. 1, p. 271-273 (January 2016) Author(s): Ginsberg, Shira, Rosner, Itzhak, Slobodin, Gleb, Boulman, Nina, Rozenbaum, Michael, Kaly, Lisa, Beyar, Ofrat Katz, Rimar, Doron Abstract: Anti-tumor necrosis factor (TNF) agents have become central players in the management of autoimmune and rheumatic disease. With the wide use of anti-TNF agents today, we have become aware of rare autoimmune complications as systemic lupus erythematosus and psoriasis, yet rarely has large vessels vasculitis been described. We herein describe a case of cytoplasmic anti-neutrophil cytoplasmic antibody (c-ANCA) (with myeloperoxidase (MPO) antibodies)-associated large vessel vasculitis (aortitis) that developed during anti-TNF treatment for ankylosing spondylitis. Awareness of this rare, but serious, adverse event of these commonly used agents in rheumatic diseases is of importance.

Title: A systematic review of interventions to improve knowledge and self-management skills concerning contraception, pregnancy and breastfeeding in people with rheumatoid arthritis. Citation: Clinical rheumatology, Jan 2016, vol. 35, no. 1, p. 33-41 (January 2016) Author(s): Ackerman, Ilana N, Ngian, Gene-Siew, Van Doornum, Sharon, Briggs, Andrew M Abstract: This systematic review aimed to determine the effectiveness of interventions for improving knowledge and/or self-management skills concerning contraception, pregnancy and breastfeeding in people with rheumatoid arthritis (RA). We searched four databases (MEDLINE, CINAHL, Cochrane Trials, PsycINFO) using a comprehensive search strategy. Studies were eligible if they were prospective, published in English from 2004 to 2015, included participants with RA and tested an intervention designed to improve knowledge and/or self-management skills relating to family planning, pregnancy or breastfeeding. As no studies met the latter criterion, the search strategy was expanded to include all prospective studies evaluating RA educational and/or self-management interventions. Data on study characteristics, participant characteristics and programme content were extracted to summarise the evidence base for interventions to support people with RA during their reproductive years. Expanded literature searches identified 2290 papers, of which 68 were eligible. Of these, nine papers (13 %) specifically excluded pregnant women/breastfeeding mothers or recruited only older people. Only one study (1 %) explicitly evaluated pregnancy-focused education via a motherhood decision aid, while eight studies (12 %) incorporated relevant (albeit minor) components within broader RA educational or self-management interventions. Of these, three studies provided methotrexate education in relation to conception/pregnancy/breastfeeding; three incorporated discussions on RA and relationships, impact of RA on the family or sexual advice; one provided information regarding contraception and fertility; and one issued a warning regarding use of biologic therapy in pregnancy/breastfeeding. In conclusion, information regarding family planning, pregnancy or breastfeeding represents a negligible part of published RA educational interventions, with scope to develop targeted resources.

Title: Minimal Clinically Important Difference as Applied in Rheumatology: An OMERACT Rasch Working Group Systematic Review and Critique. Citation: The Journal of rheumatology, Jan 2016, vol. 43, no. 1, p. 194-202, 0315-162X (January 2016) Author(s): Doganay Erdogan, Beyza, Leung, Ying Ying, Pohl, Christoph, Tennant, Alan, Conaghan, Philip G Abstract: We aimed to evaluate how minimal (clinically) important differences (MCID/MID) were calculated in rheumatology in the past 2 decades and demonstrate how the calculation is compromised by the lack of interval scaling. We conducted a systematic literature review on articles reporting MCID calculation in osteoarthritis (OA) and rheumatoid arthritis (RA) from January 1, 1989, to May 9, 2014. We evaluated the methods of MCID calculation and recorded the ranges of MCID for common patient-reported outcome measures (PROM). Taking data from the Health Assessment Questionnaire (HAQ), we showed the effects of performing mathematical calculations on ordinal data. A total of 330 abstracts were reviewed and 123 articles chosen for full text review. Thirty-six (19 OA, 16 RA and 1 OA-RA) articles were included in the final evaluation. The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) was the most frequently reported PROM with relevant calculations in OA, and the HAQ in RA. Sixteen articles used anchor-based methods alone for calculation of MCID, and 1 article used distribution-based methods alone. Nineteen articles used

both anchor and distribution-based methods. Only 1 article calculated MCID using an interval scale. Wide ranges in MCID for the WOMAC in OA and HAQ in RA were noted. Ordinal-based derivations of MCID are shown to understate true change at the margins, and overstate change in the mid-range of a scale. The anchor-based method is commonly used in the calculation of MCID. However, the lack of interval scaling is shown to compromise validity of MCID calculation.

Title: CanVasc Recommendations for the Management of Antineutrophil Cytoplasm Antibody-associated Vasculitides. Citation: The Journal of rheumatology, Jan 2016, vol. 43, no. 1, p. 97-120, 0315-162X (January 2016) Author(s): McGeoch, Lucy, Twilt, Marinka, Famorca, Leilani, Bakowsky, Volodko, Barra, Lillian, Benseler, Susan M, Cabral, David A, Carette, Simon, Cox, Gerald P, Dhindsa, Navjot, Dipchand, Christine S, Fifi-Mah, Aurore, Goulet, Michelle, Khalidi, Nader, Khraishi, Majed M, Liang, Patrick, Milman, Nataliya, Pineau, Christian A, Reich, Heather N, Samadi, Nooshin, Shojania, Kam, Taylor-Gjevre, Regina, Towheed, Tanveer E, Trudeau, Judith, Walsh, Michael, Yacyshyn, Elaine, Pagnoux, Christian, Canadian Vasculitis Research Network Abstract: The Canadian Vasculitis research network (CanVasc) is composed of physicians from different medical specialties and researchers with expertise in vasculitis. One of its aims is to develop recommendations for the diagnosis and management of antineutrophil cytoplasm antibody (ANCA)-associated vasculitides (AAV) in Canada. Diagnostic and therapeutic questions were developed based on the results of a national needs assessment survey. A systematic review of existing non-Canadian recommendations and guidelines for the diagnosis and management of AAV and studies of AAV published after the 2009 European League Against Rheumatism/European Vasculitis Society recommendations (publication date: January 2009) until November 2014 was performed in the Medline database, Cochrane library, and main vasculitis conference proceedings. Quality of supporting evidence for each therapeutic recommendation was graded. The full working group as well as additional reviewers, including patients, reviewed the developed therapeutic recommendations and nontherapeutic statements using a modified 2-step Delphi technique and through discussion to reach consensus. Nineteen recommendations and 17 statements addressing general AAV diagnosis and management were developed, as well as appendices for practical use, for rheumatologists, nephrologists, respirologists, general internists, and all other healthcare professionals more occasionally involved in the management of patients with AAV in community and academic practice settings. These recommendations were developed based on a synthesis of existing international guidelines, other published supporting evidence, and expert consensus considering the Canadian healthcare context, with the intention of promoting best practices and improving healthcare delivery for patients with AAV.

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