Latest Research Therapeutic effect of methotrexate encapsulated in cationic liposomes (EndoMTX) in comparison to free methotrexate in an antigen-induced arthritis study in vivo. Gottschalk O et al, Scand J Rheumatol. 2015 Jun 26:1-8 The authors in this study used an antigen-induced arthritis (AiA) model and investigated leukocyte- and platelet-endothelial cell interaction in arthritic female C57/Bl6 mice and in healthy controls. The arthritic animals were divided into four different groups receiving either trehalose, free MTX, EndoMTX placebo, or EndoMTX. Animals treated with EndoMTX showed a significant and superior reduction in leukocyte- and platelet-endothelial cell interaction. Free MTX or empty liposomes also showed a reduction in these parameters but not to a significant level. This study demonstrates the advantage of using MTX encapsulated in cationic liposomes in contrast to free and generic MTX, with a higher efficacy in anti-inflammatory and anti-angiogenic abilities... Clinical utility of random anti-TNF drug level testing and measurement of anti-drug antibodies on long-term treatment response in rheumatoid arthritis. Jani M et al, Arthritis Rheumatol. 2015 Jun 24 In this study, 331 patients were selected from an observational prospective cohort (n=160 adalimumab; n=171 etanercept). ADAb levels were measured using radioimmunoassay and drug levels measured using ELISA in 835 serial serum samples 3/6/12 months post-therapy initiation. ADAbs were detected in 24.8% (31/125) patients on adalimumab and no patients on etanercept completing the 12-month follow up. At 3 months, ADAb formation and low adalimumab levels were significant predictors of 12 month no EULAR response... Pharmacogenomics of Methotrexate Membrane Transport Pathway: Can Clinical Response to Methotrexate in Rheumatoid Arthritis Be Predicted? Lima A et al, Int J Mol Sci. 2015 Jun 16;16(6):13760-80. This study aims to evaluate the influence of single nucleotide polymorphisms (SNPs) on genes encoding for MTX membrane transport proteins in order to predict the clinical response to MTX.Clinicopathological data from 233 RA patients treated with MTX were collected, clinical response defined, and patients genotyped for 23 SNPs. Genotype and haplotype analyses were performed using multivariate methods and a genetic risk index (GRI) for non-response was created. The study results revealed that SLC22A11 and ABCC1 may be important to identify those patients who will not benefit from MTX treatment, highlighting the relevance in translating these results to clinical practice... Detection of Rheumatoid Arthritis-Interstitial Lung Disease Is Enhanced by Serum Biomarkers. Doyle TJ et al, Am J Respir Crit Care Med. 2015 Jun 15;191(12):1403-12. In this study, a total of 113 Brigham and Women's Hospital Rheumatoid Arthritis Sequential Study (BRASS) subjects with clinically indicated chest computed tomography scans (41% with a spectrum of clinically evident and subclinical RA-ILD) and 76 American College of Rheumatology (ACR) subjects with research or clinical scans (51% with a spectrum of RA-ILD) were selected. A combination of age, sex, smoking, rheumatoid factor, and anticyclic citrullinated peptide antibodies was strongly associated with RA-ILD (areas under the curve, 0.88 for BRASS and 0.89 for ACR). Importantly, a combinatorial signature including matrix metalloproteinase 7, pulmonary and activation-regulated chemokine, and surfactant protein D significantly increased the areas under the curve to 0.97 (P = 0.002, BRASS) and 1.00 (P = 0.016, ACR). Similar trends were seen with both clinically evident and subclinical RA-ILD... Multidrug resistance 1 (MDR1) 3435C>T gene polymorphism influences the clinical phenotype and methotrexate-induced adverse events in South Indian Tamil rheumatoid arthritis. Muralidharan N et al, Eur J Clin Pharmacol. 2015 Jun 14. The multidrug resistance 1 (MDR1) gene encodes for permeable glycoprotein (P-gp) which is an integral membrane protein for the transport of chemotherapeutic agents, immunosuppressive drugs etc. MDR1 3435C>T results in a wobble mutation in exon 26 but is associated with altered P-gp expression and reduced P-gp function. The present study was performed to determine the role of MDR1 3435C>T gene polymorphism with clinical phenotype, treatment response, and MTX adverse events in 336 RA and 329 healthy controls of South Indian Tamil ethnicity... The first double-blind, randomised, parallel-group certolizumab pegol study in methotrexate-naive early rheumatoid arthritis patients with poor prognostic factors, C-OPERA, shows inhibition of radiographic progression. Atsumi T et al, Ann Rheum Dis. 2015 Jul 2. pii: annrheumdis-2015-207511 Compared with similar studies of anti-TNF agents in MTX-naive early RA patients, the C-OPERA trial is characterised by two unique features. First, this is the first randomised controlled trial (RCT) to employ the 2010 ACR/EULAR classification criteria as the main inclusion criteria. Thus, patients enrolled in C-OPERA had very early stages of disease, strictly defined as the time from initiation of persistent arthritic symptoms identified by medical interview (RA duration ≤12 months). Second, only patients with high anti-CCP antibody titres, which is highly specific for RA, compensating for a relatively low specificity of classification criteria. Overall, clinical remission rates were relatively high in patients receiving MTX monotherapy (SDAI: 33.8%; Boolean: 28.0%; DAS28 (ESR): 36.9%) at week 52, compared with similar RCTs of biologics, but were higher in the group receiving CZP (SDAI: 57.9%; Boolean: 45.3%; DAS28 (ESR): 57.2%)... Cost-effectiveness of infliximab versus conventional combination treatment in methotrexate-refractory early rheumatoid arthritis: 2-year results of the register-enriched randomised controlled SWEFOT trial. Eriksson JK et al, Ann Rheum Dis. 2015 Jun;74(6):1094-101. In this randomized controlled trial of early, methotrexate-refractory RA, the addition of infliximab, as compared to sulfasalazine and hydroxychloroquine, resulted in higher drug and healthcare costs, while no differences were detected in productivity losses or quality-adjusted life-year (QALY) over 21 months. Irrespective of the study perspective, compared with the conventional alternative, the infliximab strategy was not found to be cost-effective at the willingness-to-pay levels generally considered acceptable (US$50 000–100 000 or £20 000–30 000 per QALY)... Late-onset neutropenia after treatment with rituximab for rheumatoid arthritis and other autoimmune diseases: data from the AutoImmunity and Rituximab registry. Salmon JH, et al. RMD Open 2015; 1:e000034. doi: 10.1136/rmdopen-2014-000034 The occurrence of late-onset neutropenia after RTX therapy was infrequent in a large prospective registry, and the related complications were moderately severe. However, the rate of late-onset neutropenia after RTX in patients with RA and other AIDs has not been clearly determined. The first important result of this study is the low rate of late-onset neutropenia after RTX in RA (1.3% of patients, 0.6/100 patient-years) and other autoimmune diseases (AIDs: 2.3%,1.5/100 patient-years) in a large multicentre registry of unselected patients. The rate observed in this study is much lower than that in the few previous reports concerning AIDs... Apremilast in Patients With Active Rheumatoid Arthritis: A Phase II, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study. Genovese MC et al, Arthritis Rheumatol. 2015 Jul; 67(7):1703-10. doi: 10.1002/art.39120. The authors in this study compared the efficacy/safety of apremilast, an oral phosphodiesterase 4 inhibitor, with placebo in patients with active rheumatoid arthritis (RA) who had an inadequate response to methotrexate (MTX). The patients were randomized 1:1:1 to receive placebo, apremilast 20 mg twice a day, or apremilast 30 mg twice a day. This study did not demonstrate a statistically significant reduction in the signs and symptoms of RA for either apremilast dose as compared with placebo when added to stable doses of MTX in patients with active RA, as measured by the ACR20 response rate (the primary efficacy end point) at week 16. The study was terminated early due to lack of clinical efficacy, and data were analyzed for the 52- week period of the study. At week 52, no trends were noted for the secondary end points by the treatment group... Pantethine Prevents Murine Systemic Sclerosis Through the Inhibition of Microparticle Shedding. Kavian N et al, Arthritis Rheumatol. 2015 Jul;67(7):1881-90. doi: 10.1002/art.39121. Endothelial cell (EC) damage in systemic sclerosis (SSc) is reflected by the shedding of microparticles (MPs). The aim of this study was to show that inhibiting MP release by using pantethine or by inactivating ATP-binding cassette transporter A1 (ABCA1) ameliorates murine SSc. The authors report that pantethine can protect ECs and fibroblasts from oxidative and nitrosative stresses through the inhibition of MP shedding and through proper antioxidant and antifibrotic properties, thus preventing the development of SSc in 2 experimental models. Because the shedding of MPs is both the consequence of EC activation and the cause of EC and fibroblast activation, the authors investigated the effects of pantethine on these 2 steps, first in vitro and then in vivo... A Clinically Based Protein Discovery Strategy to Identify Potential Biomarkers of Response to Anti-TNF-α Treatment of Psoriatic Arthritis. Collins ES et al, Proteomics Clin Appl. 2015 Jun 24. doi: 10.1002/prca.201500051 Identifying soluble biomarkers of response to therapy is an important need for complex, heterogeneous disorders such as psoriatic arthritis. This study demonstrates that candidate biomarkers may be developed by conducting proteomic analysis of synovial biopsies. The identified markers (albumin, haptoglobin, apolipoprotein AI and serum amyloid P) will need further verification and validation... Non-steroidal anti-inflammatory drug-sparing effect of tumor necrosis alpha inhibitors in early axial spondyloarthritis: Results from the DESIR cohort. Molto A et al, Arthritis Rheumatol. 2015 Jun 24. doi: 10.1002/art.39208. TNFi have made a tremendous impact in improving the signs and symptoms of AxSpA. Given the significant adverse effects associated with NSAID therapy, a NSAID sparing effect may be desirable but has not been evaluated in pivotal SpA clinical trials. This study demonstrated that TNFi indeed have a NSAID sparing effect. However, the adverse impact of NSAIDs in AxSpA and the need for NSAID sparing effect warrants further evaluation... A Randomized, Double-blind, Placebo-controlled, 16-Week Study of Subcutaneous Golimumab in Patients with Active Non-radiographic Axial Spondyloarthritis. Sieper J et al, Arthritis Rheumatol. 2015 Jul 2. doi: 10.1002/art.39257. Golimumab is a TNFi with known efficacy in AS. The current study demonstrates the efficacy of golimumab in active non-radiographic AxSpA. Thus, all available TNFi have now shown to be effective for both AS and nr-AxSpA... Secukinumab, a human anti-interleukin-17A monoclonal antibody, in patients withpsoriatic arthritis (FUTURE 2): a randomised, double-blind, placebo-controlled, phase 3 trial. McInnes IB, Lancet. 2015 Jun 26. pii: S0140-6736(15)61134-5. Around 30% of patients with PsA fail to respond to TNFi therapy. Moreover, secondary failure rates remain high. Newer treatment options for those who fail TNFi therapy or in whom TNFi therapy is contraindicated are an important perceived need amongst clinicians and patients. Secukinumab, an anti IL-17A antibody, has shown promise in the treatment of peripheral arthritis of PsA. The drug has also been shown to be efficacious in the management of AS and psoriasis. Thus, the drug seems to have efficacy in all domains of PsA and is an important addition to the PsA drug armamentarium... Distribution of Peripheral Lymphocyte Populations in Primary Sjögren's Syndrome Patients. Sudzius G et al, J Immunol Res. 2015;2015:854706. Most patients with Sjogren’s syndrome are antibody positive and hence the B cell population in the antibody positive subset would be expected to be high. In this study, the investigators have looked at the other lymphocyte subsets in these patients and curiously found low level so of CD3(+) T cells, Th17 population, CD8(+) T cell absolute counts and NKT and NK cell population while the Treg cell population was unaffected. The absolute CD4(+)T was also different than in controls. Whether these parameters are different in different stages of the disease and are affected by treatment and whether genetic polymorphisms are responsible for these will need to be studied... ACPA-positive primary Sjögren’s syndrome: true primary or rheumatoid arthritis-associated Sjögren’s syndrome? Payet J, et al. RMD Open 2015; 1:e000066. doi:10.1136/rmdopen-2015-000066 This study is one of the largest series of ACPA-positive patients with pSS with a well-defined phenotype and a prospective follow-up, focusing on their outcome and on identification of risk factors of evolution to RA. The study results showed that almost half of these patients developed RA, most of them with typical erosive X-ray changes and had the diagnosis reconsidered as RA with associated SS after a median follow-up of 8 years. The only parameter associated with evolution to RA was the elevation of acute phase reactants... Autoantibody profiling can predict primary Sjögren's syndrome years before diagnosis and identify those with early onset and severe disease course. Theander E et al, Arthritis Rheumatol. 2015 Jun 24. doi: 10.1002/art.39214. Autoantibody production is a dominant feature of pSS, but very little is known about the time point at which such production begins. The authors in this study addressed this issue. ANA, RF, and antibodies against Ro60/SSA and Ro52/SSA could be detected in samples collected as early as 19–20 years (median 4.3–5.1) before diagnosis, whereas the corresponding figure for antibodies against La/SSB was 16 years (median 3.5). Interestingly in 95% of the patients who expressed prediagnostic autoantibodies and in all those who expressed autoantibodies before the first symptoms , these antibodies were present in the earliest available serum sample. Thus, clearly the antibodies were present earlier than our calculations can prove, i.e., even earlier than 2 decades before diagnosis. .. Clinical Characteristics and Outcome of Primary Sjogren's Syndrome: A Large Asian Indian Cohort. Sandhya P et al, Open Rheumatol J. 2015 Jun 26;9:36-45. Patients with Primary Sjogren’s syndrome from the subcontinent may be different from the Western population. This retrospective analysis by investigators from CMC Vellore found two groups of patients – one with high systemic complications and high antibody titers needing aggressive immunosuppressive therapy and another one with mild symptoms, mainly sicca and chronic pain, and not infrequently seronegative. There were lesser cases of cryoglobulinemia, Raynaud’s phenomenon, hypergammaglobulinemia and this cohort had younger patients. Interestingly only about 8% of patients actually complained of sicca themselves. An epidemiologic study to pick up more and more patients from the general population is the need of the hour as most patients with sicca may never be reaching tertiary care centers... A B-cell activating factor receptor (BAFF-R) His159Tyr mutation in Sjögren's Syndrome related lymphoproliferation. Papageorgiou A et al, Arthritis Rheumatol. 2015 Jun 19.doi: 10.1002. Patients with Sjogren’s syndrome are prone to develop lymphomas, especially B cell ones and MALT lymphomas. While we know the phenotype of patients likely to develop lymphomas (high globulins, low complements, recurrent parotitis etc), not much is known about the genotype of these patients. The investigators here have looked at the His159Tyr mutation of the BAFF – R (receptor) and found it to be more frequent in patients than controls and also more in Sjogrens patients than lupus and RA. Younger patients with MALT lymphomas carried the mutation even more frequently. Whether these mutations or others also would define response to rituximab or other B depleting therapies will need to be studied... Three percent diquafosol ophthalmic solution as an additional therapy to existing artificial tears with steroids for dry-eye patients with Sjögren's syndrome. Yokoi N et al, Eye (Lond).2015 Jul 10.doi: 10.1038/eye.2015.125. Dry eye is a significant problem. Many patients with Sjogrens’s syndrome suffer from this condition. Topical treatment, while available is far from satisfactory. Systemic therapies are not uniformly recommended for just dry eye symptoms and their results too are dubious. The investigators in this small study have used 3% diquafosol in these patients and found it to be effective both in terms of subjective symptoms (redness, fatigue, foreign body sensation) and objective analysis (tear meniscus radius, tear film break up time and corneal epithelial staining) for upto 12 months. More and more studies in different populations around the globe are needed to validate the use of this drug for the treatment for dry eye...