Disease-modifying Anti-rheumatic Therapy Research Articles

Utilization of Biologic Disease-Modifying Antirheumatic Therapy in Patients With Rheumatoid Arthritis and Recently Diagnosed Breast Cancer.

Biologic disease-modifying antirheumatic drugs (bDMARDs) are immunosuppressants, and there have been concerns that they might impact tumor immunity in patients with cancer with rheumatoid arthritis (RA). The purpose of this study was to describe the utilization trends of bDMARD in patients with RA after breast cancer (BC) diagnosis. We performed a retrospective cohort study of adults with RA and BC (2008 onward) from Optum's de-identified Clinformatics® Data Mart Database (CDM); the Surveillance, Epidemiology, and End Results Program (SEER) Medicare; and the Texas Cancer Registry (TCR) Medicare databases. We evaluated bDMARD utilization trends during the first three years after BC. We conducted multivariable logistic regression to evaluate the association of utilizationwith patient characteristics. A total 1,412 patients were identified in CDM and 1,439 patients in SEER/TCR-Medicare. During the three months before BC diagnosis, 28.2% (CDM) and 26.9% (SEER/TCR-Medicare) patients had received bDMARDs. Within the first three years after diagnosis, 24.1% (CDM) and 26.4% (SEER/TCR-Medicare) were receiving bDMARDs. About 70% of the patients in the two cohorts received glucocorticoids with no significant time trend increases. The largest predictor of bDMARD utilization was prior use before BC (CDM: odds ratio [OR] 27.15, 95% confidence interval [CI] 19.29-38.19; SEER/TCR: OR 18.98, 95% CI 13.72-26.26). Regional and distant BC compared to in situ or localized were also associated with lower bDMARDs utilization in SEER/TCR-Medicare (OR 0.54, 95% CI 0.36-0.82; OR 0.31, 95% CI 0.13-0.77, respectively). The utilization of tumor necrosis factor inhibitors and other bDMARDs in patients with RA and recent BC has not increased since 2008. Glucocorticoids utilization remained high. The largest predictor of bDMARD utilization was prior use before BC.

Evaluation of Anti-Inflammatory and Anti-Arthritic Activities of AV11-03 in Female Rats

Rheumatiod arthritis is a systemic auto-immune disease characterized by chronic inflammation at multiple synovial joints, cartilage destruction and bone erosion. Currently available non-steroidal anti-inflammatory drugs, cortico-steroids and disease modifying anti-rheumatic therapies have severe side effects on prolonged use and thus throw a challenge for development of safe, effective alternatives. Of the many plant drugs claimed to be effective in the treatment of rheumatoid arthritis, in depth studies were carried out on the fruits of Terminalia chebula (Haradae) and the oleo-gum resin of Boswellia serrata (Sallaki). Glucosamine was shown to be chondrio-protective and effective in osteo-arthritis. Hence, we tested ‘AV-11 03’ which is a combination of the extracts of haradae, salliki an maize glucosamine on acute and chronic inflammatory models by studying a battery of physical, biochemical, histological and radiological parameters.

Antibody response to the COVID-19 ChAdOx1nCov-19 and BNT162b vaccines after temporary suspension of DMARD therapy in immune-mediated inflammatory disease: an extension study (RESCUE 2)

The persistence of immunogenicity in patients with immune-mediated inflammatory diseases (IMID) on disease-modifying antirheumatic therapy (DMARD) has been less well studied. This extension study evaluates the SARS-CoV2 antibody decay kinetics...

2022 American College of Rheumatology/American Association of Hip and Knee Surgeons Guideline for the Perioperative Management of Antirheumatic Medication in Patients With Rheumatic Diseases Undergoing Elective Total Hip or Total Knee Arthroplasty.

To develop updated guidelines for the perioperative management of disease-modifying medications for patients with rheumatic diseases, specifically those with inflammatory arthritis (IA) and those with systemic lupus erythematosus (SLE), undergoing elective total hip arthroplasty (THA) or elective total knee arthroplasty (TKA). We convened a panel of rheumatologists, orthopedic surgeons, and infectious disease specialists, updated the systematic literature review, and included currently available medications for the clinically relevant population, intervention, comparator, and outcomes (PICO) questions. We used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology to rate the quality of evidence and the strength of recommendations using a group consensus process. This guideline updates the 2017 recommendations for perioperative use of disease-modifying antirheumatic therapy, including traditional disease-modifying antirheumatic drugs, biologic agents, targeted synthetic small-molecule drugs, and glucocorticoids used for adults with rheumatic diseases, specifically for the treatment of patients with IA, including rheumatoid arthritis and spondyloarthritis, those with juvenile idiopathic arthritis, or those with SLE who are undergoing elective THA or TKA. It updates recommendations regarding when to continue, when to withhold, and when to restart these medications and the optimal perioperative dosing of glucocorticoids. This updated guideline includes recently introduced immunosuppressive medications to help decision-making by clinicians and patients regarding perioperative disease-modifying medication management for patients with IA and SLE at the time of elective THA or TKA.

2022 American College of Rheumatology/American Association of Hip and Knee Surgeons Guideline for the Perioperative Management of Antirheumatic Medication in Patients With Rheumatic Diseases Undergoing Elective Total Hip or Total Knee Arthroplasty.

To develop updated guidelines for the perioperative management of disease-modifying medications for patients with rheumatic diseases, specifically those with inflammatory arthritis (IA) and those with systemic lupus erythematosus (SLE), undergoing elective total hip arthroplasty (THA) or elective total knee arthroplasty (TKA). We convened a panel of rheumatologists, orthopedic surgeons, and infectious disease specialists, updated the systematic literature review, and included currently available medications for the clinically relevant population, intervention, comparator, and outcomes (PICO) questions. We used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology to rate the quality of evidence and the strength of recommendations using a group consensus process. This guideline updates the 2017 recommendations for perioperative use of disease-modifying antirheumatic therapy, including traditional disease-modifying antirheumatic drugs, biologic agents, targeted synthetic small-molecule drugs, and glucocorticoids used for adults with rheumatic diseases, specifically for the treatment of patients with IA, including rheumatoid arthritis and spondyloarthritis, those with juvenile idiopathic arthritis, or those with SLE who are undergoing elective THA or TKA. It updates recommendations regarding when to continue, when to withhold, and when to restart these medications and the optimal perioperative dosing of glucocorticoids. This updated guideline includes recently introduced immunosuppressive medications to help decision-making by clinicians and patients regarding perioperative disease-modifying medication management for patients with IA and SLE at the time of elective THA or TKA.

2022 American College of Rheumatology/American Association of Hip and Knee Surgeons Guideline for the Perioperative Management of Antirheumatic Medication in Patients With Rheumatic Diseases Undergoing Elective Total Hip or Total Knee Arthroplasty

To develop updated American College of Rheumatology/American Association of Hip and Knee Surgeons guidelines for the perioperative management of disease-modifying medications for patients with rheumatic diseases, specifically those with inflammatory arthritis (IA) and those with systemic lupus erythematosus (SLE), undergoing elective total hip arthroplasty (THA) or elective total knee arthroplasty (TKA). We convened a panel of rheumatologists, orthopedic surgeons, and infectious disease specialists, updated the systematic literature review, and included currently available medications for the clinically relevant population, intervention, comparator, and outcomes (PICO) questions. We used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology to rate the quality of evidence and the strength of recommendations using a group consensus process. This guideline updates the 2017 recommendations for perioperative use of disease-modifying antirheumatic therapy, including traditional disease-modifying antirheumatic drugs, biologic agents, targeted synthetic small-molecule drugs, and glucocorticoids used for adults with rheumatic diseases, specifically for the treatment of patients with IA, including rheumatoid arthritis and spondyloarthritis, those with juvenile idiopathic arthritis, or those with SLE who are undergoing elective THA or TKA. It updates recommendations regarding when to continue, when to withhold, and when to restart these medications and the optimal perioperative dosing of glucocorticoids. This updated guideline includes recently introduced immunosuppressive medications to help decision-making by clinicians and patients regarding perioperative disease-modifying medication management for patients with IA and SLE at the time of elective THA or TKA.

AB1074 FATAL BUT PREVENTABLE - SINGLE CENTRE SERIES OF 6 CASES OF PNEUMOCYSTIS JIROVECII PNEUMONIA (PJP) IN PATIENTS WITH AUTO-IMMUNE INFLAMMATORY RHEUMATIC DISEASE (AIIRD) IN ONE YEAR.

BackgroundPneumocystis jirovecii pneumonia (PJP) is an uncommon but frequently fatal fungal infection, which can affect patients with rheumatic diseases treated with immunosuppressants or high doses of steroids. There are no clear guidelines on when to prescribe primary prophylaxis and available agreements differ depending on the disease or immunosuppressant.ObjectivesTo raise awareness about this preventable infection and to highlight the urgent need to create a tailored probability scoring, before starting any immunosuppression so that the risk benefit of prophylaxis can be objectively assessed.MethodsThis is a retrospective case series of six patients who developed definite or probable PJP known to the Rheumatology Department at Oxford University Hospitals NHS FT since the beginning of 2021. These patients were identified through the microbiology and infectious disease teams, and notes were reviewed to collate data regarding the clinical characteristics. Of these, five were being treated for large vessels vasculitis (LVV) whilst the other one had seropositive rheumatoid arthritis (RA). The diagnosis of PJP was made on clinical picture, laboratory results, bronchoscopy and CT findings.ResultsIn this series, the median age was 78 years (range 55-93) with equal gender distribution. In three LVV patients, the diagnosis was confirmed on ultrasound, one had a positive PET-CT whilst the other case had a high probability clinical diagnosis. Comorbidities included chronic kidney disease and hypertension in three patients, diabetes, or previous underlying malignancy in other two. Smoking history was present in four patients, while five patients had lymphopenia with counts <1x10^9/L. Four of the six cases were on combined therapy with disease modifying anti-rheumatic therapy drugs (DMARDs) and prednisolone, only one was exclusively on prednisolone and the patient with RA was on Methotrexate and Humira.The chronology of the infection was variable, still most of the patients developed PJP infection during the first three months of starting either a biologic or corticosteroids. The median steroids dose by the time of PJP infection was 30 mg and unfortunately three of the patients died. None of the patients who developed PJP had been given antibiotic prophylaxis prior to infection.Some proposed scoring systems for serious infection risk in patients with AIIRD exist, however they focused on RA or biologics use rather than patients with vasculitis or connective tissue disorders who might be on high dose corticosteroids. Additionally, PJP prophylaxis is not recommended in any of the current guidelines for LVV management (BSR, EULAR, ACR). Cochrane review suggests reduction of risk by 85% in patients given prophylaxis.ConclusionPneumocystis Jirovecii pneumonia (PJP) prophylaxis is not current practice for patients with large vessel vasculitis. Consideration needs to be given to PJP prophylaxis for patients on high dose steroids for a prolonged period, particularly in the presence of other risk factors. More data will be needed to help establish guidelines on PJP primary prophylaxis.

Vaccine Efficacy after Rituximab Exposure: First Interim Analysis of Virtue Project on Behalf of West Midlands Research Consortium, UK

▪Background: Anti-CD20 B cell depleting agents are amongst the most commonly used immunotherapeutics employed in the treatment of haematological malignancy and autoimmune diseases. By inducing peripheral B cell aplasia, anti-CD20 depleting agents are hypothesised to significantly impair serological responses to neoantigens, including the SARS-CoV-2 spike glycoprotein within SARS-CoV-2 vaccines. Seropositivity following SARS-CoV-2 is the strongest, measurable correlate of protection from severe COVID-19. Understanding the kinetics of B cell reconstitution and vaccine responsiveness following exposure to B cell depleting agents is essential to maximise vaccine efficacy in patients vulnerable to severe COVID-19.Methods: 80 patients with underlying haematological malignancy and 38 patients with underlying rheumatological disease previously treated with anti-CD20 B cell depleting agents were studied following their second dose of a SARS-CoV-2 vaccine (median time to sampling: 46.5d, IQR: 33.8-63.3). Lymphocyte subset (CD4, CD8, CD19, CD56/16) enumeration was performed using 6 colour flow cytometry (BD Trucount). Total anti-SARS-CoV-2 spike glycoprotein antibodies were measured by enzyme-linked immunosorbent assay (The Binding Site, Human Anti-IgG/A/M SARS-CoV-2-ELISA). The relationship between immune reconstitution following B cell depletion and vaccine responsiveness was explored.Results: In the haematology cohort (median age 70y, IQR 60.3-76.0, 62.5% male), overall seropositivity following vaccination was 60.0%. Individuals on active chemotherapy had significantly lower seroprevalence than those vaccinated following the completion of chemotherapy (22.7% vs 74.1%, p<0.0001). In the rheumatology cohort (median age 65y, IQR 58.3-70.8, 39.9% male), overall seropositivity was 69.4%. In both cohorts, vaccine non-responders had significantly smaller populations of peripheral CD19+ B cells (haematology: 0.20 vs 0.02 x10 9/L, p=0.004, rheumatology: 0.07 vs 0.01 x10 9/L, p=0.03). The magnitude of the antibody response following vaccination did not differ between recipients of Tozinameran and Vaxzeveria in either cohort. Vaccine responsiveness was lower in the first 6 months following B cell depletion therapy; 42.9% in the haematology cohort and 33.3% in the rheumatology cohort, increasing to 100% and 75% respectively in individuals receiving their second dose 6-12 months following B cell depletion (Figure 1).B cell reconstitution in the 7-12 month window following B cell depletion was faster in haematology compared to rheumatology patients (77.8% v 22.2% achieving normal B cell count, p=0.005) and associated with improved vaccine responsiveness. However, persistent immunodeficiency occurred in some haematology patients following completion of treatment: 25% of patients who had completed therapy at least 36 months previously failed to respond to vaccination. In this cohort of vaccine non-responders, 83.3% of individuals had B cell numbers within the normal range. These patients had all previously been treated for follicular lymphoma suggesting a specific mechanism for long-range secondary immunodeficiency in these patients.Conclusions: Serological responsiveness to SARS-CoV-2 vaccines is poor during active chemotherapy for haematological malignancy and in the first 6 months following B cell depletion, regardless of underlying disease. Vaccine responsiveness significantly improves in the 7-12 month window following B cell depletion. Compared to haematology patients, B cell reconstitution is slower in rheumatology patients and associated with reduced vaccine responsiveness, possibly due to the use of additional concurrent disease-modifying anti-rheumatic therapies. Furthermore, long-term secondary immunodeficiency occurs in a minority of haematology patients. To maximise the efficacy from SARS-CoV-2 booster vaccination and optimal utilisation of available vaccine doses, immunisations should be delivered at least 6 months following the administration of anti-CD20 depleting drugs.Figure 1: Kinetics of return of vaccine responsiveness following B cell depletion in haematology and rheumatology patients. [Display omitted] DisclosuresPaneesha: Roche: Honoraria; Janssen: Honoraria; Gilead: Honoraria; Bristol Myers Squibb: Honoraria; AbbVie: Honoraria; Celgene: Honoraria. Drayson: Abingdon Health: Current holder of individual stocks in a privately-held company.

Overall survival in patients with rheumatoid arthritis and solid malignancies receiving biologic disease-modifying antirheumatic therapy.

The effects of biologic disease-modifying antirheumatic drugs (bDMARDs) in patients with rheumatoid arthritis (RA) and cancer are largely unknown. We examined overall survival (OS) in patients with RA and solid malignancies receiving bDMARDs. We performed a retrospective cohort study of patients with RA and solid malignancies seen at MD Anderson Cancer Center between 2002 and 2014. Cox proportional hazard regression models, stratified by tumor type and stage, were fit evaluating use of bDMARDs as a time fixed and time varying covariate. We identified 431 RA patients with solid malignancies: 111 (26%) received bDMARDs after their cancer diagnosis. Median OS from cancer diagnosis was 16.1years. Of the patients receiving bDMARDs, most had localized disease, and only 14 (13%) had advanced cancer. In the stratified Cox models no statistically significant differences were observed between patients who received tumor necrosis factor inhibitors (TNFi) or patients who received nonTNFi, compared with those who did not receive bDMARDs (hazard ratio (HR), 0.67; 95% confidence interval (CI), 0.31, 1.44; HR, 1.10; 95% CI, 0.26, 4.60 respectively). In breast cancer patients, those receiving TNFi or nonTNFi had a numerically higher but statistically nonsignificant HR compared with those who did not receive bDMARD: HR, 1.40 (95% CI, 0.42, 4.73), and HR, 1.37 (95% CI, 0.22, 8.42) respectively. No significant differences in OS were observed between patients who received bDMARDs and those who did not. Additional data is needed to evaluate other cancer outcomes such as recurrence and progression, and patients with advanced cancer. Key Points •We found no statistically significant differences in OS between patients with RA and concomitant solid malignancies who received bDMARDs and those who did not. •Most patients who received bDMARDs had been diagnosed with early stage cancer •As few patients with advanced cancer received bDMARDs safety for this group cannot be established •No significant differences were observed between TNFi and nonTNFi, but the sample size was small.

Effectiveness and safety of secukinumab in axial spondyloarthritis and psoriatic arthritis: A retrospective analysis of its real-world usage from India

Background: Although secukinumab has become available in India since mid-2016, there is no published data on its usage in axial spondyloarthritis (axial SpA) and psoriatic arthritis (PsA). In this study, we analyzed the real-world usage of this drug to assess the effectiveness and safety in axial SpA and PsA. Methods: All patients with active axial SpA or PsA who had received secukinumab as a biological disease-modifying antirheumatic therapy either as a primary or as a secondary biological therapy covering the period between August 2017 and February 2020 from five Indian centers were included in the study. Whereas Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) 50 and Ankylosing Spondylitis Disease Activity Score (ASDAS) C-reactive protein (CRP) improvement were used to assess the treatment response in axial SpA, DAS 28ESR was used for PsA. The data were retrospectively analyzed. Results: Out of 45 patients included in the study, 27 had axial SpA and 18 had PsA. Disease duration (median [interquartile range]) was 60 (96) months in axial SpA and 54 (108) in PsA. In axial SpA, out of 21 patients who had completed at least 6 months of therapy, 19 demonstrated a BASDAI 50 response and 20 reported good response as per ASDAS CRP (15, low disease activity and 5, inactive disease). In PsA, 14 patients had completed at least 6 months of therapy and 8 of them went in remission and another 4 achieved low disease activity. Adverse events were few (2, upper respiratory tract infection; 1 pneumonia; 3, uveitis; and leukocytoclastic vasculitis in 1) with no tuberculosis reported. Conclusion: In its real-life usage to treat both active axial SpA and PsA, secukinumab was found to be effective and safe.

A prediction rule for lack of achievement of inactive disease with methotrexate as the sole disease-modifying antirheumatic therapy in juvenile idiopathic arthritis

BackgroundTo investigate the frequency of achievement of inactive disease (ID) in children with juvenile idiopathic arthritis (JIA) treated with methotrexate (MTX) as the sole disease-modifyng antirheumatic (DMARD) therapy and to develop a prediction model for lack of attainment of ID.MethodsThe clinical charts of consecutive patients started with MTX as the sole DMARD between 2000 and 2013 were reviewed. Patient follow-up was censored at first episode of ID or, in case ID was not reached, at last follow-up visit or when a biologic DMARD was prescribed. The characteristic at MTX start of patients who achieved or did not achieve ID were compared with univariate and multivariable analyses. Regression coefficients (β) of variables that entered the best-fitting logistic regression model were converted and summed to obtain a “prediction score” for lack of achievement of ID.ResultsA total of 375 patients were included in the study. During MTX administration, 8.8% were given systemic corticosteroids and 44.1% intra-articular corticosteroids. After MTX start, 229 (61%) patients achieved ID after a median of 1.7 years, whereas 146 patients (39%) did not reach ID after a median of 1.2 years. On multivariable analysis, independent correlations with lack of achievement of ID were identified for the disease categories of systemic arthritis, enthesitis-related arthritis (ERA) and polyarthritis and C-reactive protein (CRP) > 1.4 mg/dl. The prediction score ranged from 0 to 3 and its cutoff that discriminated best between patients who achieved or did not achieve ID was > 0.5. The categories of systemic arthritis or ERA, both of which had a score greater than 0.5, were sufficient alone to predict a lower likelihood to reach ID. Polyarthritis and increased CRP, whose score was 0.5, assumed a predictive value only when present in association.ConclusionA conventional treatment regimen based on MTX as the sole DMARD led to achievement of ID in a sizeable proportion of children with JIA. Our findings help to outline the characteristics of patients who may deserve a synthetic DMARD other than MTX or the introduction of a biologic DMARD from disease outset.

Multimodal [18 F]FDG PET/CT Is a Direct Readout for Inflammatory Bone Repair: A Longitudinal Study in TNFα Transgenic Mice.

ABSTRACTIn rheumatoid arthritis (RA), chronic joint inflammation leading to bone and cartilage damage is the major cause of functional impairment. Whereas reduction of synovitis and blockade of joint damage can be successfully achieved by disease modifying antirheumatic therapies, bone repair upon therapeutic interventions has only been rarely reported. The aim of this study was to use fluorodeoxyglucose ([18F]FDG) and [18F]fluoride µPET/CT imaging to monitor systemic inflammatory and destructive bone remodeling processes as well as potential bone repair in an established mouse model of chronic inflammatory, erosive polyarthritis. Therefore, human tumor necrosis factor transgenic (hTNFtg) mice were treated with infliximab, an anti‐TNF antibody, for 4 weeks. Before and after treatment period, mice received either [18F]FDG, for detecting inflammatory processes, or [18F]fluoride, for monitoring bone remodeling processes, for PET scans followed by CT scans. Standardized uptake values (SUVmean) were analyzed in various joints and histopathological signs of arthritis, joint damage, and repair were assessed. Longitudinal PET/CT scans revealed a significant decrease in [18F]FDG SUVs in affected joints demonstrating complete remission of inflammatory processes due to TNF blockade. In contrast, [18F]fluoride SUVs could not discriminate between different severities of bone damage in hTNFtg mice. Repeated in vivo CT images proved a structural reversal of preexisting bone erosions after anti‐TNF therapy. Accordingly, histological analysis showed complete resolution of synovial inflammation and healing of bone at sites of former bone erosion. We conclude that in vivo multimodal [18F]FDG µPET/CT imaging allows to quantify and monitor inflammation‐mediated bone damage and reveals not only reversal of synovitis but also bone repair upon TNF blockade in experimental arthritis. © 2019 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals, Inc.

Cytosolic group IVA phospholipase A2 inhibitors, AVX001 and AVX002, ameliorate collagen-induced arthritis

BackgroundCytosolic phospholipase A2 group IVA (cPLA2α)-deficient mice are resistant to collagen-induced arthritis, suggesting that cPLA2α is an important therapeutic target. Here, the anti-inflammatory effects of the AVX001 and AVX002 cPLA2α inhibitors were investigated.MethodsIn vitro enzyme activity was assessed by a modified Dole assay. Effects on inhibiting IL-1β-induced release of arachidonic acid (AA) and prostaglandin E2 (PGE2) were measured using SW982 synoviocyte cells. In vivo effects were studied in prophylactic and therapetic murine collagen-induced arthritis models and compared to methotrexate (MTX) and Enbrel, commonly used anti-rheumatic drugs. The in vivo response to treatment was evaluated in terms of the arthritis index (AI), histopathology scores and by plasma levels of PGE2 following 14 and 21 days of treatment.ResultsBoth cPLA2α inhibitors are potent inhibitors of cPLA2α in vitro. In synoviocytes, AVX001 and AVX002 reduce, but do not block, release of AA or PGE2 synthesis. In both CIA models, the AI and progression of arthritis were significantly lower in the mice treated with AVX001, AVX002, Enbrel and MTX than in non- treated mice. Several histopathology parameters of joint damage were found to be significantly reduced by AVX001 and AVX002 in both prophylactic and therapeutic study modes; namely articular cavity and peripheral tissue inflammatory cell infiltration; capillary and synovial hyperplasia; articular cartilage surface damage; and periostal and endochondral ossification. In comparison, MTX did not significantly improve any histopathology parameters and Enbrel only improved ossification. Finally, as a biomarker of inflammation and as an indication that AVX001 and AVX002 blocked the cPLA2α target, we determined that plasma levels of PGE2 were significantly reduced in response to the AVX inhibitors and MTX, but not Enbrel.ConclusionsAVX001 and AVX002 display potent anti-inflammatory activity and disease-modifying properties in cellular and in vivo models. The in vivo effects of AVX001 and AVX002 were comparable to, or superior, to those of MTX and Enbrel. Taken together, this study suggests that cPLA2α inhibitors AVX001 and AVX002 are promising small molecule disease-modifying anti-rheumatic therapies.

Management of hepatitis B and C infections in rheumatologic disease.

Hepatitis B and C viruses present dual considerations in rheumatic disease as both etiologic factors and important comorbidities that must be assessed and addressed. This review summarizes the link between hepatitis B and arthritis and polyarteritis nodosa as well as hepatitis C and arthritis, Sicca syndrome and cryoglobulinemic vasculitis. Recent data pertaining to the antiviral management in these conditions, especially regarding the use of the direct-acting antivirals in hepatitis C, are also presented. Additionally, guidance on testing and treatment of hepatitis B and C as comorbidities in the context of systemic inflammatory rheumatic conditions and the use of disease-modifying antirheumatic therapy are discussed.

Rheumatoid arthritis and risk of cardiovascular disease.

In developing countries, rheumatoid arthritis (RA) remains a seriously under-prioritised disease, particularly among the underprivileged, often resulting in presentation of patients late in the course of their disease, further complicated by limited therapeutic options and inconsistent follow up. The consequences are often severe with irreversible disability, increased frequency of co-morbidities, especially cardiovascular disease (CVD), and higher mortality rates, relative to developed countries. Despite addressing traditional cardiovascular risk factors, the impact of subclinical or 'residual' inflammation from uncontrolled RA needs to be considered. This narrative review explores the prevalence and pathogenesis of CVD in RA, including the impact of tobacco use. It discusses pitfalls in the risk assessment of CVD in patients with RA, and the effect of disease-modifying anti-rheumatic therapy on cardiovascular co-morbidity.

Psoriatic arthritis: novel targets add to a therapeutic renaissance

Psoriasis is the most common chronic autoinflammatory skin disease, affecting 2–3% of the world's population, of whom 10–30% have psoriatic arthritis. As a result of better elucidation of crucial pathogenic inflammatory pathways and the advent of biologic disease-modifying anti-rheumatic therapies, the treatment of psoriatic arthritis has undergone a renaissance.

Is current smoking status and its relationship to anti-cyclic citrullinated peptide antibodies a predictor of worse response to biological therapies in rheumatoid arthritis patients?

Objective: To assess the association between smoking, anti-cyclic citrullinated peptide (anti-CCP) antibody status, and clinical efficacy of biological therapies in rheumatoid arthritis (RA) patients.Method: This retrospective clinical practice setting study included 1349 RA patients from the METEOR database (aged >18 years). We collected data on sociodemographics, smoking status (smoker, <10, 10–19, and >20 cigarettes/day; ex-smoker; non-smoker), baseline disease activity parameters and anti-CCP, previous disease-modifying anti-rheumatic drugs (DMARDs), biological therapy, combined therapy (steroids and DMARDs), and follow-up disease activity. Clinical efficacy was assessed by European League Against Rheumatism (EULAR) good/moderate response rates for all aggregated biological therapies, based on both smoking and anti-CCP status.Results: The non-smoking RA patients were more often female at biological therapy initiation than the ex-smokers and smokers (91.1% vs 60.4% and 67.9%, respectively, p < 0.001), and ex-smokers were older than non-smokers and smokers (mean ± sd 56.5 ± 11.1, 53.5 ± 13.3 and 51.3 ± 11.0 years old, respectively; p < 0.001). In total, 845 (62.6%) were non-smokers, 214 (15.9%) ex-smokers, and 290 (21.5%) smokers [daily cigarettes smoked: 148 (11%) <11; 61 (4.5%) 11–20; and 81 (6%) >20]. Anti CCP-antibody status was similar in both groups. Non-smokers showed higher baseline DAS28 than ex-smokers and smokers (5.0 ± 1.5 vs 4.7 ± 1.4 and 4.7 ± 1.4, respectively; p < 0.001) and used more baseline steroids and DMARDs. A higher EULAR response rate was observed in non-smokers than in ex-smokers and smokers (73% vs 65% and 64.1%, respectively; p = 0.004). Drug survival was higher in non-smokers compared to ex-smokers and smokers [57.7 months (46.4–53.8), 38.6 (30.3–46.8), and 50.1 (41.8–58.4); p < 0.001, respectively].Conclusion: In daily clinical practice, non-smokers respond better than smokers to biological therapy, but this does not result in better drug survival.

Risk of malignancy in patients with rheumatic disorders

Abstract Patients with autoimmune rheumatic diseases including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), Sjogren’s syndrome (SS), and inflammatory myositis are at increased risk of developing malignancies. Treatment of these conditions, including disease-modifying anti-rheumatic drugs (DMARDs) and biologic therapies, are also associated with increased risk of malignancies.Cancer adds to the disease burden in these patients, affecting their quality of life and life expectancy. The decision in choosing immunosuppressive agents in these rheumatic diseases should take into account the disease severity, expectation for disease control, comorbidities, as well asthe side effects including risks of cancer. This article does not include the risk of malignancy in patients with the idiopathic inflammatory myopathies, which are well-recognized paraneoplastic conditions.

The marked and rapid therapeutic effect of tofacitinib in combination with subcutaneous methotrexate in a rheumatoid arthritis patient with poor prognostic factors who is resistant to standard disease-modifying antirheumatic drugs and biologicals: A clinical case

Today, it is generally accepted that it is necessary to achieve clinical remission in rheumatoid arthritis (RA) or as minimum a low disease activity. The paper describes a clinical case of a female patient diagnosed with RA who was observed to have inefficiency of standard disease-modifying antirheumatic therapy with methotrexate 25 mg/week, secondary inefficiency of tumor necrosis factor-α inhibitors (adalimumab), and inefficiency/poor tolerance of the interlukin-6 receptor antagonist tocilizumab. This determined the need to use fofacitinib (TOFA), a drug with another mechanism of action. TOFA is the first agent from a new group of immunomodulatory and anti-inflammatory drugs, intracellular kinase inhibitors. Disease remission could be achieved during therapy with TOFA, which enables one to consider this synthetic drug as a therapy option that potentially competes with therapy with biologicals.

Advances in the management of rheumatoid arthritis

Modern early rheumatoid arthritis strategies are usually based upon a number of important overarching principles: 1. early diagnosis facilitates early commencement of disease modifying anti-rheumatic therapy; 2. early commencement of treatment reduces the long-term risk of erosive damage and functional decline; 3. composite disease activity measures should be used to quantify global rheumatoid arthritis disease activity; and 4. therapy should be intensified until a predefined disease activity target has been achieved. A substantial minority of rheumatoid arthritis patients (approximately 40%) will experience an adequate response to methotrexate monotherapy; however, the remainder may require disease modifying anti-rheumatic combination therapy, and/or biologic therapy, to achieve disease activity targets. Importantly, short term trials of methotrexate monotherapy do not appear to disadvantage outcomes provided treatment continues to be intensified if disease activity targets are not achieved.