Therapeutic Advances in Musculoskeletal Disease

Therapeutic Advances in Musculoskeletal Disease

The role of epigenetics and immunological imbalance in the etiopathogenesis of psoriasis and psoriatic arthritis

06-11-2019 – Lukas Frischknecht,Matteo Vecellio,Carlo Selmi

A cross-sectional investigation into the association between Porphyromonas gingivalis and autoantibodies to citrullinated proteins in a German population

05-11-2019 – Kolade Oluwagbemigun,Tülay Yucel-Lindberg,Thomas Dietrich,Gregory Tour,Natalia Sherina,Monika Hansson,Manuela Bergmann,Karin Lundberg,Heiner Boeing

Mortality risk prediction in lupus patients complicated with invasive infection in the emergency department: LUPHAS score

05-11-2019 – Wanlong Wu,Jun Ma,Yuhong Zhou,Chao Tang,Feng Zhao,Fangfang Sun,Wenwen Xu,Jie Chen,Shuang Ye,Yi Chen

Balancing benefits and risks in the era of biologics

24-10-2019 – Giovanni Adami,Kenneth G. Saag,Roland D. Chapurlat,Nuria Guañabens,Glenn Haugeberg,Willem F. Lems,Radmila Matijevic,Nicola Peel,Denis Poddubnyy,Piet Geusens

Zoledronic acid plus methylprednisolone versus zoledronic acid or placebo in symptomatic knee osteoarthritis: a randomized controlled trial

23-10-2019 – Guoqi Cai,Laura L Laslett,Dawn Aitken,Flavia Cicuttini,Lyn March,Catherine Hill,Tania Winzenberg,Graeme Jones

Cardiovascular risk factors in psoriatic disease: psoriasis versus psoriatic arthritis

16-10-2019 – Nuria Barbarroja,Iván Arias-de la Rosa,Clementina López-Medina,María del Rosario Camacho-Sánchez,Ignacio Gómez-García,Antonio José Vélez-García,Alejandro Escudero-Contreras,Chary López-Pedrera,María Dolores López-Montilla,Eduardo Collantes-Estévez

Journal Article

A randomized, phase IIa study to assess the systemic exposure of triamcinolone acetonide following injection of extended-release triamcinolone acetonide or traditional triamcinolone acetonide into both knees of patients with bilateral knee osteoarthritis

16-10-2019 – Alan Kivitz,Louis Kwong,Tammi Shlotzhauer,Joelle Lufkin,Amy Cinar,Scott Kelley

Journal Article

Intra-articular corticosteroids are commonly used for pain relief in patients with knee osteoarthritis. Simultaneous intra-articular corticosteroid (CS) knee injections may be beneficial for the ~80-90% of patients who present with, or develop, bilateral knee osteoarthritis, but concurrent injections may increase systemic CS exposure and data on safety/tolerability are lacking. Triamcinolone acetonide extended release (TA-ER) has shown decreased systemic triamcinolone acetonide exposure compared with traditional triamcinolone acetonide crystalline suspension (TAcs) after a single knee injection in patients with knee osteoarthritis. This phase IIa study was designed to assess the safety and systemic triamcinolone acetonide exposure following injections of TA-ER or TAcs into each knee of patients with bilateral knee osteoarthritis. Patients (⩾40 years) meeting American College of Rheumatology criteria for knee osteoarthritis in both knees received concurrent single intra-articular injections of TA-ER 32 mg or TAcs 40 mg into each knee (total: 64 mg and 80 mg, respectively) and were followed for 6 weeks. Safety was evaluated based on treatment-emergent adverse events (TEAEs). Blood samples for pharmacokinetic analysis were collected pre-injection, and at the following postinjection time points: 1, 2, 3, 4, 5, 6, 8, 10, 12, and 24 h, and days 8, 15, 29, and 43. Baseline characteristics were balanced between patients randomly assigned to TA-ER ( In patients with bilateral knee osteoarthritis, intra-articular injection of TA-ER into both knees was well tolerated. Consistent with pharmacokinetic profiles observed after a single knee injection, plasma triamcinolone acetonide concentrations were lower after bilateral TA-ER injections compared with the higher and more variable concentrations observed after bilateral TAcs injections. NCT03378076.

Indicator opportunistic infections after biological treatment in rheumatoid arthritis, 10 years follow-up in a real-world setting

08-10-2019 – Leticia Leon,Marina Peñuelas,Francisco Javier Candel,Dalifer Freites,Luis Rodriguez-Rodriguez,Benjamin Fernandez-Gutierrez,Juan Angel Jover,Lydia Abasolo

Journal Article

This research describes the incidence and factors associated with opportunistic infections in rheumatoid arthritis (RA) patients treated with biological disease-modifying antirheumatic drugs (b
DMARDs). A retrospective longitudinal study was carried out from 2007 to 2018. We included RA patients treated with a tumor necrosis factor (TNF)-targeted b
DMARD or non-TNF-targeted b
DMARD from the start of b
DMARDs. An independent variable was the development of an indicator of opportunistic infection after biological (IOIb) treatment. Secondary variables included sociodemographic, clinical, and treatments. We used survival techniques to estimate the incidence of IOIb, per 1000 patient-years (95% CI). We performed a Cox multivariate regression analysis model to compare the risk of IOIb. Results were expressed as a hazard ratio (HR). A total of 441 RA patients were included, that started 761 different courses of b
DMARDs. A total of 81% were women with a mean age at first b
DMARD of 57.3 ± 14 years. A total of 71.3% of the courses were TNF-targeted b
DMARDs and 28.7% were non-TNF-targeted b
DMARDs. There were 37 IOIb (25 viral, 6 fungal, 5 bacterial, 1 parasitic). Nine of these required hospitalization and one died. The global incidence of IOIb was 23.2 (16.8-32). TNF-targeted b
DMARDs had 25 IOIb, incidence 20.5 (13.9-30.4), and non-TNF-targeted b
DMARDs had 12 IOIb, incidence 31.7 (18-55.9). In the multivariate analysis, glucocorticosteroids (HR 2.17, The incidence of IOIb due to b
DMARDs was 23 cases per 1000 patient-years. Close monitoring should be taken in the RA patients treated with b
DMARDs and glucocorticosteroids, mainly in elderly patients and those with a low total lymphocyte count at the beginning of b
DMARD treatment.

Update on the safety and efficacy of teriparatide in the treatment of osteoporosis

05-10-2019 – Salvatore Minisola,Cristiana Cipriani,Giada Della Grotta,Luciano Colangelo,Marco Occhiuto,Piergianni Biondi,Chiara Sonato,Evelina Vigna,Mirella Cilli,Jessica Pepe

Journal Article, Review

Following the completion of the Fracture Prevention Trial, teriparatide was approved by the United States Food and Drug Administration and the European Medicine Agency as the first therapeutic anabolic agent for the treatment of postmenopausal women with severe osteoporosis. It subsequently received additional approval for the treatment of osteoporosis in men, and for the treatment of osteoporosis associated with glucocorticoid therapy in men and women at risk of fracture. In this review, we summarize the most important data concerning PTH 1-34 therapy before 2016 in the treatment of osteoporosis, and report some outstanding results published in the last 2 years. New data on safety will also discussed, together with the state of art of nonclassical utilization. Finally, in view of the recent approval of biosimilars, possible future landscapes are discussed.

Autologous costal chondral transplantation and costa-derived chondrocyte implantation: emerging surgical techniques

23-09-2019 – Youshui Gao,Junjie Gao,Hengyuan Li,Dajiang Du,Dongxu Jin,Minghao Zheng,Changqing Zhang

Journal Article, Review

It is a great challenge to cure symptomatic lesions and considerable defects of hyaline cartilage due to its complex structure and poor self-repair capacity. If left untreated, unmatured degeneration will cause significant complications. Surgical intervention to repair cartilage may prevent progressive joint degeneration. A series of surgical techniques, including biological augmentation, microfracture and bone marrow stimulation, autologous chondrocyte implantation (ACI), and allogenic and autogenic chondral/osteochondral transplantation, have been used for various indications. However, the limited repairing capacity and the potential pitfalls of these techniques cannot be ignored. Increasing evidence has shown promising outcomes from ACI and cartilage transplantation. Nevertheless, the morbidity of autologous donor sites and limited resource of allogeneic bone have considerably restricted the wide application of these surgical techniques. Costal cartilage, which preserves permanent chondrocytes and the natural osteochondral junction, is an ideal candidate for the restoration of cartilage defects. Several

Biological therapies and their clinical impact in the treatment of systemic lupus erythematosus

20-09-2019 – Rosalie Magro

Journal Article, Review

The development of biological therapies has had an impact on the management of several medical conditions. Their use in systemic lupus erythematosus (SLE), however, remains very limited. This review has summarized the evidence on the clinical effect of biologicals in SLE. Biological drugs with a number of targets have been studied in several phase II and III randomized controlled trials (RCTs). Positive results have been obtained in phase III RCTs with belimumab and this led to its license for active SLE. The clinical experience with belimumab has confirmed the efficacy and safety of belimumab in SLE. Promising results have been noted in phase II trials for blisibimod, sifalimumab, anifrolumab, and ustekinumab. Despite the fact that the RCTs with rituximab did not achieve their primary endpoint, clinical experience with rituximab is extensive and shows favorable clinical response in refractory renal and non-renal SLE. It is hoped that further ongoing phase III RCTs on a number of biological agents in SLE will highlight the potential role of other biologicals in the management of this challenging and heterogeneous condition.

Glucocorticoid-induced osteoporosis: from clinical trials to clinical practice

20-09-2019 – Giovanni Adami,Elizabeth J Rahn,Kenneth G Saag

Journal Article, Review

Glucocorticoid-induced osteoporosis (GIOP) is the most common form of secondary osteoporosis. To date, six large randomized controlled clinical trials on the efficacy of pharmaceutical treatment in GIOP have been conducted. All of these studies have focused predominately on bone mineral density outcomes, and none of them have been statistically powered to address fracture endpoints. The purpose of this review is to highlight differences in the design and results within these large randomized GIOP clinical trials, and how these differences might affect clinical decisions. Differences between studies in trial design, populations studied, and variable efficacy impact the comparability and generalizability of these findings, and ultimately should affect practitioners’ behavior. We review the clinical trials that provide the best quality evidence on comparative efficacy and safety of GIOP treatments. We also propose suggestions on the design of future GIOP clinical trials with attention to improved generalizability, and, ideally, study designs that might achieve fracture outcomes.

The effectiveness of Kinesio Taping® for pain management in knee osteoarthritis: a randomized, double-blind, controlled clinical trial

29-08-2019 – Venta Donec,Raimondas Kubilius

Journal Article

Kinesio Taping® method is a nonpharmacological alternative for pain management in musculoskeletal disorders. However, the existing evidence is insufficient to assess its full effectiveness for pain management in knee osteoarthritis (KO). Our aim was to evaluate the effectiveness of the Kinesio Taping method in reducing knee pain for KO patients. In this randomized, double blind, controlled trial, we recruited 187 patients with grade I-III KO who were allocated to either the Kinesio Taping or control group. The study was carried out in outpatient facility. Either Kinesio Taping or nonspecific taping was applied on the affected knee area for 4 weeks. Pain evaluation was performed at baseline, after 1 month of taping and after 1 further month without taping. The data on usage of painkillers were collected; Numeric Pain Rating Scale; an algometer, and Knee injury and Osteoarthritis Outcome Scores (KOOS) pain subscale were used to assess pain. Tolerance and subjective opinions toward the effectiveness of taping were evaluated. The chosen level of significance was The majority (>70%) of both groups’ patients indicated that tapes reduced the knee pain. The reported use of painkillers decreased, in addition to self-reported increase in the KOOS subscale, thereby indicating pain alleviation. All self-reported improvement remained at the 1-month follow up ( Elastic taping can safely relieve knee pain and reduce the need for pharmacological management in KO. A specific Kinesio Taping technique is clinically more beneficial for knee-pain alleviation in comparison with nonspecific taping.[Clinical identifier: NCT03076177.].

When rheumatology and infectious disease come together

22-08-2019 – George E Fragoulis,Nikolaos V Sipsas


Therapeutic approaches to osteosarcopenia: insights for the clinician

07-08-2019 – Mizhgan Fatima,Sharon L. Brennan-Olsen,Gustavo Duque

Journal Article, Review

Osteopenia/osteoporosis and sarcopenia are both age-related conditions. Given the well-defined bone and muscle interaction, when osteopenia and sarcopenia occur simultaneously, this geriatric syndrome is defined as ‘osteosarcopenia’. Evidence exists about therapeutic interventions common to both bone and muscle, which could thereby be effective in treating osteosarcopenia. In addition, there are roles for common nonpharmacological strategies such as nutritional intervention and physical exercise prescription in the management of this condition. In this review we summarize the evidence on current and upcoming therapeutic approaches to osteosarcopenia.

Update on the management of hypophosphatasia

01-08-2019 – V. Choida,J. S. Bubbear

Journal Article, Review

Hypophosphatasia is a rare inherited disease caused by a loss of function mutations in the gene that codes for the tissue-nonspecific alkaline phosphatase enzyme. It is autosomally inherited and at least 388 different genetic defects have been identified. The clinical presentation is variable from a severe perinatal form, that is fatal if untreated, to adult-onset disease. This review covers the pathophysiology, diagnosis and current management option including the recently licensed enzyme replacement therapy asfotase alfa.

The role of microbiome in rheumatoid arthritis treatment

30-07-2019 – Rahul Bodkhe,Baskar Balakrishnan,Veena Taneja

Journal Article, Review

Rheumatoid arthritis (RA) is an autoimmune disorder with multifactorial etiology; both genetic and environmental factors are known to be involved in pathogenesis. Treatment with disease-modifying antirheumatic drugs (DMARDs) plays an essential role in controlling disease progression and symptoms. DMARDs have immunomodulatory properties and suppress immune response by interfering in various pro-inflammatory pathways. Recent evidence has shown that the gut microbiota directly and indirectly modulates the host immune system. RA has been associated with dysbiosis of the gut microbiota. Patients with RA treated with DMARDs show partial restoration of eubiotic gut microbiome. Hence, it is essential to understand the impact of DMARDs on the microbial composition and its consequent influences on the host immune system to identify novel therapies for RA. In this review, we discuss the importance of antirheumatic-drug-induced host microbiota modulations and possible probiotics that can generate eubiosis.

Update on novel pharmacological therapies for osteoarthritis

23-07-2019 – Asim Ghouri,Philip G. Conaghan

Journal Article, Review

Osteoarthritis (OA) is a chronic painful arthritis with increasing global prevalence. Current management involves non-pharmacological interventions and commonly used pharmacological treatments that generally have limited analgesic efficacy and multiple side effects. New treatments are therefore required to relieve patient symptoms and disease impact. A number of existing pharmacological therapies have been recently trialled in OA. These include extended-release triamcinolone and conventional disease-modifying anti-rheumatic drugs (DMARDs) used in the management of rheumatoid arthritis; generally, DMARDs have not shown a benefit in treating OA. Novel analgesic therapies are in development, including those targeting peripheral pain pathways. Disease-modifying osteoarthritis drugs (DMOADs) target key tissues in the OA pathophysiology process and aim to prevent structural progression; a number of putative DMOADs are in phase II development. There is preliminary evidence of structural improvement with some of these therapies but without concomitant symptom improvement, raising new considerations for future DMOAD trials.

Thrombocytosis as a prognostic factor in polymyalgia rheumatica: characteristics determined from cluster analysis

19-07-2019 – Keigo Hayashi,Keiji Ohashi,Haruki Watanabe,Ken-Ei Sada,Kenta Shidahara,Yosuke Asano,Sumie Hiramatsu Asano,Yuriko Yamamura,Yoshia Miyawaki,Michiko Morishita,Yoshinori Matsumoto,Tomoko Kawabata,Jun Wada

Journal Article

This study aimed to identify the clinical subgroups of polymyalgia rheumatica (PMR) using cluster analysis and compare the outcomes among the identified subgroups. We enrolled patients with PMR who were diagnosed at Okayama University Hospital, Japan between 2006 and 2017, met the 2012 European League Against Rheumatism/American College of Rheumatology provisional classification criteria for PMR, and were treated with glucocorticoids. Hierarchical cluster analysis using variables selected by principal component analysis was performed to identify the clusters. Subsequently, the outcomes among the identified clusters were compared in the study. The primary outcome was treatment response at 1 month after commencement of treatment. The secondary outcome was refractory clinical course, which was defined as the requirement of additional treatments or relapse during a 2-year observational period. A total of 61 consecutive patients with PMR were enrolled in the study. Their mean age was 71 years, and 67% were female. Hierarchical cluster analysis revealed three distinct subgroups: cluster 1 ( Thrombocytosis could predict the clinical course in patients with PMR.

Helpful, albeit hazardous! Esophageal stem-cell injection in systemic sclerosis

17-07-2019 – Franziska Durchschein,Florentine Moazedi-Fuerst,Sonja Kielhauser,Angelika Lackner,Maria Wiedner,Horst Koch,Ivo Justich,Andreas Eherer

Case Reports

Over 90% of patients with systemic sclerosis suffer from gastroesophageal reflux. Esophageal motility disturbances are associated with a reduced life quality and may force interstitial lung disease progression. We wanted to determine whether we can improve gastroesophageal reflux in these patients by esophageal stem-cell injection. We performed a pilot study including eights patients with systemic sclerosis and symptomatic gastroesophageal reflux. Sampling of adipose tissue was performed by an experienced plastic surgeon under local anesthesia. The collected fat was injected into the submucosa of the distal esophagus, each time 1 ml in all four quadrants starting 2, 4 and 6 cm proximal to the Z line (ending up to a total volume of 12 ml). Before the intervention, 3, 6 and finally 12 months after the procedure, patients answered the Gastroesophageal Reflux Disease Health-Related Quality of Life Questionnaire (GERD HRQL) and a high-resolution manometry was performed to quantify changes in motility function. All patients showed an improvement in the GERD HRQL score after the stem-cell injection and a lower dosage of proton-pump inhibitors. The manometric findings showed no change throughout the time. A serious adverse event occurred, as one patient developed multiple cerebellar embolic infarcts. Because of the favorable effect in all patients, a safe route for esophageal fat injection needs to be developed.

Does periodontitis represent a risk factor for rheumatoid arthritis? A systematic review and meta-analysis

10-07-2019 – Railson de Oliveira Ferreira,Raíra de Brito Silva,Marcela Baraúna Magno,Anna Paula Costa Ponte Sousa Carvalho Almeida,Nathália Carolina Fernandes Fagundes,Lucianne Cople Maia,Rafael Rodrigues Lima

Journal Article, Review

Periodontitis is an inflammatory disease of dental supporting tissues (gingiva, periodontal ligament, and bone) and it has been suggested as a possible etiology for rheumatoid arthritis (RA). In this systematic review, we aim to verify if periodontitis represents a risk factor for RA. Electronic databases were consulted until March 2018 considering eligibility criteria focusing on: (P, participants) adults; (E, exposure) with periodontitis; (C, comparison) without periodontitis; and (O, outcome) development of RA. Quality assessment of studies and risk-of-bias evaluation were also performed. To undertake a quantitative analysis, the number of persons with RA and a total number of participants for the case group (with periodontitis) and control group (without periodontitis) were used to calculate the odds ratio (OR) with a 95% confidence interval (CI). A total of 3888 articles were identified, and nine studies were considered eligible. Seven of 9 articles suggested an association among diseases by the common pro-inflammatory profiles. The pooled analysis of 3 articles showed a higher RA prevalence for persons with periodontitis (

Functional risk for fracture by safe functional motion testing: a short version of the safe functional motion test

24-06-2019 – Christopher P. Recknor,Daniel Van Dussen,Norma MacIntyre,Julie Recknor

Journal Article

‘Unsafe’ movement strategies used to perform everyday activities were quantified using scores for tasks included in the Short Form Safe Functional Motion test series (SSFM). Baseline scores were independently associated with incident fractures after adjusting for factors known to effect fracture risk. The purpose of the present study is to determine whether the SSFM, a series of tests of habitual motion, is associated with incident fragility fracture at any skeletal sites. An osteoporosis clinic database was queried for adults with baseline SSFM scores and corresponding data for prevalent fractures, femoral neck bone mineral density (fn
BMD), osteoporosis medication use, and incident fractures at 1-year and 3-year follow ups [ An Sfm-3 score was a significant independent predictor of any fracture at 1 year [adjusted odds ratio (95% CI) = 1.118 (1.025, 1.219) for each 10-point decrease in Sfm-3; Scores on the SSFM predict fracture risk such that for each 10-point drop in score the odds of fracture are increased by up to 18% independent of risk associated with age, bone mineral density, use of bone-sparing medications, and history of a fracture.

Real-world data on secukinumab use for psoriatic arthritis and ankylosing spondylitis

19-06-2019 – Ashley Elliott,Gary Wright

Journal Article

Is there a role for cherries in the management of gout?

17-05-2019 – Marcum W. Collins,Kenneth G. Saag,Jasvinder A. Singh

Journal Article, Review

Despite the availability of effective urate-lowering therapy (ULT) and anti-inflammatory drugs for the treatment of gout, there is considerable interest in novel treatment approaches. Patients with gout often have a multitude of comorbidities, leading to concern over drug-drug interactions and medication adverse events. The cherry is a small nutrient-rich fruit that has garnered a great deal of attention in recent years as a nonpharmacologic option for the treatment of a multitude of disease manifestations. Perhaps a quarter of patients with gout try cherries or cherry products to treat their gout, which have antioxidant and anti-inflammatory (IL-6, TNF-α, IL-1β, IL-8, COX-I and -II) properties, hypouricemic effects, and the ability to downregulate NFk
B-mediated osteoclastogenesis. Based on these properties, cherries may reduce both the acute and chronic inflammation associated with recurrent gout flares and its chronic destructive arthropathy. In this review, we explore the potential benefits of cherries and cherry products as a nonpharmacologic option for the treatment of gout.

Corticosteroid injections for knee osteoarthritis are supported by the literature: in the affirmative

27-04-2019 – Nicolas S. Piuzzi,Michael A. Mont

Journal Article

Recent developments in advanced imaging in gout

16-04-2019 – Joseph Davies,Philipp Riede,Kirsten van Langevelde,James Teh

Journal Article, Review

The plain radiographic features of gout are well known; however, the sensitivity of plain radiographs alone for the detection of signs of gout is poor in acute disease. Radiographic abnormalities do not manifest until late in the disease process, after significant joint and soft tissue damage has already occurred. The advent of dual-energy computed tomography (DECT) has enabled the non-invasive diagnosis and quantification of gout by accurately confirming the presence and extent of urate crystals in joints and soft tissues, without the need for painful and often unreliable soft tissue biopsy or joint aspiration. Specific ultrasound findings have been identified and may also be used to aid diagnosis. Both ultrasound and magnetic resonance imaging (MRI) may be used for the measurement of disease extent, monitoring of disease activity or treatment response, although MRI findings are nonspecific. In this article we summarize the imaging findings and diagnostic utility of plain radiographs, ultrasound, DECT, MRI and nuclear medicine studies in the assessment as well as the implications and utility these tools have for measuring disease burden and therapeutic response.

New-onset cutaneous sarcoidosis under tocilizumab treatment for giant cell arteritis: a quasi-paradoxical adverse drug reaction. Case report and literature review

12-04-2019 – Rosaria Del Giorno,Alfonso Iodice,Cristina Mangas,Luca Gabutti

Case Reports

New-onset sarcoidosis has been previously described in three case reports in patients affected by rheumatoid arthritis treated with tocilizumab (TCZ). The existence of a cause-effect mechanism between the biological treatment and the onset of the illness is still being debated. A 74-year-old woman was diagnosed with giant cell arteritis (GCA). The first-line treatment with glucocorticoids; and the second-line with methotrexate and low-dose glucocorticoids were stopped due to multiple pathological vertebral fractures and insufficient biological and clinical response. The cytotoxic agent, cyclophosphamide, was then introduced and in turn stopped, because of gastrointestinal side effects. Thereafter a treatment with TCZ was begun. The patient experienced good clinical response; however, 8 months later she developed painful hyper-pigmented reddish cutaneous micronodular lesions localized to the abdomen and thorax. A cutaneous biopsy was performed, and histological analysis showed noncaseating epithelioid granulomas in the hypodermis. The diagnosis of cutaneous sarcoidosis was made. Topical corticosteroids were administered and, as requested by the patient, TCZ was discontinued with slow but complete resolution of the skin lesions. After TCZ discontinuation however, the GCA flared and the patient’s symptoms and biological abnormalities reappeared. Thus, after a 6-month suspension, TCZ was re-administered. At 2 months later the skin lesions compatible with cutaneous sarcoidosis reappeared. Topical corticosteroids were once again prescribed and as suggested by the patient the TCZ posology was reduced. The patient’s symptoms disappeared, and the cutaneous lesions resolved. The time elapsed from TCZ treatment start and the onset of cutaneous sarcoidosis, as well as its recurrence after TCZ suspension and rechallenge supported the diagnosis of a drug-induced reaction. To the best of our knowledge, this case report represents the first instance of cutaneous sarcoidosis most likely induced by TCZ in patients affected by GCA. In addition, our case emphasizes that although TCZ in monotherapy confirms to be an effective treatment for GCA, further immunological disorders could be unmasked, and the discussed side effect of the drug could be dose-dependent.

Effectiveness and safety of certolizumab pegol in rheumatoid arthritis patients in Canadian practice: 2-year results from the observational FαsT-CAN study

05-03-2019 – Louis Bessette,Boulos Haraoui,Andrew Chow,Isabelle Fortin,Sanjay Dixit,Majed Khraishi,Derek Haaland,Sami Elmoufti,Fabienne Staelens,Irina Bogatyreva,Jerry Syrotuik,Saeed Shaikh

Journal Article

The aim of this study was to assess the real-world effectiveness and safety of certolizumab pegol (CZP) in rheumatoid arthritis (RA) patients, and the impact on patients’ productivity, pain, and fatigue, in Canadian practice. Fαs
T-CAN, a 2-year prospective, observational study, evaluated CZP use in Canadian adults with moderate to severe, active RA. The primary objective was to assess the proportion of patients achieving 28-joint Disease Activity Scores (DAS28) <2.6 at Week 104. Secondary and additional endpoints assessed the improvements in Patients' Assessment of Arthritis Pain (Pt
AAP), fatigue, Health Assessment Questionnaire-Disability Index (HAQ-DI), and the proportion of patients achieving minimal clinically important differences (MCID) in HAQ-DI. Validated arthritis-specific Work Productivity Surveys (WPS-RA) assessed the RA-associated impact on productivity. Incidence of CZP-related treatment-emergent adverse events (TEAEs) was reported for patients receiving ⩾1 dose of CZP (safety set). The full analysis set (baseline DAS28 ⩾ 2.6, ⩾1 dose of CZP and ⩾1 valid post-baseline DAS28 measurement) included 451 of the 546 patients recruited into the study; a total of 229/451 (50.8%) patients completed Week 104. At Week 104, 90/451 (20.0%) patients achieved DAS28 < 2.6. Rapid improvements in disease activity, pain, and fatigue were observed. At Week 104, 66.2% of patients achieved HAQ-DI MCID. Patients employed at Week 104, reported reduced absenteeism, and improved productivity. CZP-related TEAEs were consistent with the known CZP safety profile. CZP was an effective RA treatment in Canadian practice, and no new CZP-related safety signals were identified. The improvements in household and workplace productivity are the first observations in a real-world Canadian setting.

Serum chitotriosidase and neopterin levels in patients with ankylosing spondylitis

02-03-2019 – Ferdi Yavuz,Bilge Kesikburun,Özlem Öztürk,Ümüt Güzelküçük

Journal Article

The aim of this study was to assess the serum chitotriosidase (Ch
T) and neopterin levels in patients with ankylosing spondylitis (AS) and to evaluate whether serum Ch
T and neopterin levels are related to disease activity. A total of 86 patients with AS were included in the study. Patients were divided into two groups based on Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) scores: The active AS patients group included 40 patients who had a BASDAI score ⩾4. The inactive AS patients group included 46 patients who had a BASDAI score <4. We compared the serum level of erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), Ch
T and neopterin between the two groups. Active AS patients had significantly higher ESR, CRP, serum Ch
T and neopterin levels compared with the inactive AS patients group ( The present study emphasized that serum Ch
T levels can be useful in the determination of the disease activity of AS patients.

IL-12/IL-23p40 identified as a downstream target of apremilast in ex vivo models of arthritis

23-02-2019 – Tue W. Kragstrup,Mary Adams,Søren Lomholt,Morten A. Nielsen,Line D. Heftdal,Peter Schafer,Bent Deleuran

Journal Article

Apremilast (Otezla Synovial fluid was obtained from patients with active rheumatoid arthritis (RA), Ps
A or peripheral spondyloarthritis (Sp
A; In SFMCs cultured for 48 h, apremilast decreased the production of interleukin (IL)-12/IL-23p40 (the shared subunit of IL-12 and IL-23), colony-stimulating factor 1, CD6, and CD40 and increased the production of C-X-C motif chemokine 5 dose-dependently. Apremilast had a very different response signature compared with the tumor necrosis factor alpha inhibitor adalimumab with a substantially greater inhibition of IL-12/IL-23p40. In SFMCs cultured for 21 days, apremilast increased the secretion of IL-10. In FLS cultures, apremilast decreased matrix metalloproteinase-3 production. Apremilast decreased osteoclastogenesis but did not affect mineralization by human osteoblasts. This study reveals the downstream effects of apremilast in

Health effects of direct triaging to physiotherapists in primary care for patients with musculoskeletal disorders: a pragmatic randomized controlled trial

16-02-2019 – Lena Bornhöft,Maria EH Larsson,Lena Nordeman,Robert Eggertsen,Jörgen Thorn

Journal Article

Physiotherapists and general practitioners (GPs) both act as primary assessors for patients with musculoskeletal disorders in primary care. Previous studies have shown that initial triaging to physiotherapists at primary healthcare centres has advantages regarding efficiency in the work environment and utilization of healthcare. In this study, we aimed primarily to determine whether triaging to physiotherapists affects the progression of health aspects over time differently than traditional management with initial GP assessment. The secondary aim was to determine whether triaging to physiotherapists affects patients’ attitudes of responsibility for musculoskeletal disorders. This was a pragmatic trial where both recruitment and treatment strategies were determined by clinical, not study-related parameters, and was initiated at three primary care centres in Sweden. Working-age patients of both sexes seeking primary care for musculoskeletal disorders and nurse assessed as suitable for triaging to physiotherapists were randomized to initial consultations with either physiotherapists or GPs. They received self-assessment questionnaires before the initial consultation and were followed up at 2, 12, 26 and 52 weeks with the same questionnaires. Outcome measures were current and mean (3 months) pain intensities, functional disability, risk for developing chronic musculoskeletal pain, health-related quality of life and attitudes of responsibility for musculoskeletal conditions. Trends over time were analysed with a regression model for repeated measurements. The physiotherapist-triaged group showed significant improvement for health-related quality of life at 26 weeks and showed consistent but nonsignificant tendencies to greater reductions of current pain, mean pain in the latest 3 months, functional disability and risk for developing chronic pain compared with traditional management. The triage model did not consistently affect patients’ attitudes of responsibility for musculoskeletal disorders. Triaging to physiotherapists for primary assessment in primary care leads to at least as positive health effects as primary assessment by GPs and can be recommended as an alternative management pathway for patients with musculoskeletal disorders. NCT148611.

Current advances in the treatment of giant cell arteritis: the role of biologics

13-02-2019 – Candice Low,Richard Conway

Journal Article, Review

Giant cell arteritis (GCA) is the most common form of systemic vasculitis. It is a potentially severe disease with 25% of patients suffering vision loss or stroke. Our treatment paradigm is based on glucocorticoids. Glucocorticoids are required in high doses for prolonged periods and subsequently are associated with a significant amount of treatment-related morbidity. Alternative treatment options are urgently needed to minimize these glucocorticoid adverse events. Many other agents, such as methotrexate and tumour necrosis factor alpha inhibitors have been used in GCA, with limited or no evidence of benefit. Our emerging understanding of the pathogenic processes involved in GCA has led to an increased interest in the use of biologic agents to treat the disease. Two randomized controlled trials have recently reported dramatic effects of the use of the interleukin-6 targeted biologic tocilizumab in GCA, with significant increases in remission rates and decreases in glucocorticoid burden. While encouraging, longer-term and additional outcomes are awaited to clarify the exact positioning of tocilizumab in the treatment approach. Emerging data for other biologic agents, particularly abatacept and ustekinumab, are also encouraging but less well advanced. We are at the dawn of a new era in GCA treatment, but uncertainties and opportunities abound.