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ID PMID Title PublicationDate abstract
26678914 The role of synthetic drugs in the biologic era: therapeutic strategies for treating juven 2016 INTRODUCTION: Juvenile idiopathic arthritis is the most frequent chronic rheumatic disease in childhood. Synthetic disease modifying drugs (DMARDs) have been used in its treatment since the 1980s and have led to substantial improvement of quality of life and disease outcome. Recent pharmacological research has focused on newer medications, especially biologic agents. AREAS COVERED: Synthetic DMARDS, especially methotrexate, rightfully remain the first-line treatment of most categories of juvenile arthritis, as attested by several international guidelines. A substantial body of evidence supports these medications, and recent research tries to clarify their optimal use in the clinical setting, both as monotherapy and in combination with biologics. In addition, new forms of synthetic DMARDs are in the research pipeline, or are already used for rheumatoid arthritis. EXPERT OPINION: Methotrexate remains the preferred first-line medication for polyarticular arthritis, with leflunomide as a viable alternative in case of intolerance or toxicity, despite lack of approval in Europe and the US. Sulfasalazine and hydroxychloroquine are used only rarely in clinical practice, considered in combination with methotrexate if biologics are not available. New synthetic DMARDS are in the research pipeline for JIA, in the form of small molecules.
27335685 Methotrexate-associated primary cutaneous CD30-positive cutaneous T-cell lymphoproliferati 2016 Methotrexate (MTX) is a commonly used anti-metabolite agent. Increased risk of lymphoproliferative disorders (LPD) in patients with rheumatoid arthritis (RA) has been documented with the prolonged use of immunosuppressive medications such as MTX. This is thought to be the result of immune dysregulation and/or chronic immune stimulation. Most cases of LPDs regress following withdrawal of the offending immunosuppressive agent. We present an interesting and rare case of CD30 and EBV positive CD8 primary cutaneous anaplastic large cell lymphoma (PC-ALCL) in a 66-year-old African American woman. Patient had been on MTX for rheumatoid arthritis (RA) which was stopped after the patient was evaluated at our institution. Patient had an incredible response to stopping immunosuppression with spontaneous regression of skin lesions and disappearance of clonal malignant cell population as evidenced on serial biopsy specimens. Primary cutaneous CD30+ LPDs constitute about 30% of the primary cutaneous T-cell lymphomas (CTLs) and includes entities such as lymphomatoid papulosis (LyP), primary cutaneous anaplastic large cell lymphoma (PC-ALCL) and other CD30+ borderline LPDs. Histopathological criteria in addition to CD30 positivity is important for identification of these conditions. Treatment options include "wait and see", phototherapy, radiotherapy, topical agents, systemic therapy and surgical resection. Prognosis is excellent and most cases resolve spontaneously on withdrawal of immunosuppression. Refractory cases may require aggressive local treatment or systemic therapy. Brentuximab Vedontin, an anti-CD30 antibody drug conjugate (ADC), may provide additional therapeutic option in refractory cases.
26379753 Systemic Review and Meta-Analysis of the Clinical Efficacy and Adverse Effects of Zhengqin 2015 Chinese medicines are gaining wider acceptance. They have been used for treating rheumatoid arthritis (RA) for thousands of years, and the need to investigate the interaction between Chinese medicines and western medicines is widely recognized. In this study, a large number of RCTs and CCTs were analyzed to systematically assess the effects and adverse events of Zhengqing Fengtongning (ZQFTN) for RA. Eleven studies that contained 956 participants (508 in the treatment group; 448 in the control group) were included. The results showed that although ZQFTN combined with methotrexate MTX could not decrease the swollen joint count and tender joint count of RA patients better than MTX alone, the combination therapy might relieve the duration of morning stiffness (SMD: -16.06; 95% CI: -28.77 to -3.34), reduce laboratory indexes (RF: SMD: -10.84; 95% CI: -19.39 to -2.29; ESR: SMD: -7.26; 95% CI: -11.54 to -2.99; CRP: SMD: -3.66; 95% CI: -5.94 to -1.38), and improve the overall effect (RR: 1.08; CI: 1.01 to 1.16) better than monotherapy. The combination therapy was significantly better in controlling adverse drug reactions (RR: 0.60; 95% CI: 0.46 to 0.79). Through this systematic review, we found that ZQFTN combined with MTX for the treatment of RA might have better clinical efficacy than MTX only and might be superior in terms of controlling adverse drug reactions.
26962613 2015 Aug Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by joint swelling, joint tenderness, and destruction of synovial joints, leading to severe disability and premature mortality. The prevalence of RA in Canada is about 1%. The pharmacological therapy of RA aims to achieve remission and, if remission is not possible, to minimize disease activity while controlling symptoms, halting damage, preventing disability, and improving quality of life. Non-biologic synthetic disease-modifying antirheumatic drugs (DMARDs) have been shown to alter the clinical course of RA and slow or halt radiographic progression when used early and aggressively in the treatment of RA. Methotrexate is the preferred DMARD with respect to efficacy and safety and is recommended as first-line DMARD treatment in patients with RA unless contraindicated or not tolerated. Based on Canadian Rheumatology Association guidelines, if patients do not attain the desired target within three to six months of non-biologic DMARD therapy, treatment with a biologic therapy should be initiated. Tocilizumab (TCZ) is a recombinant humanized anti-human interleukin (IL)-6 receptor monoclonal antibody. It blocks the pleiotropic cytokine IL-6, which is found at high levels in the joints affected by RA. In Canada, TCZ is available as 162 mg/0.9 mL solution in single-use pre-filled syringes for subcutaneous (SC) injection, and in single-use vials containing 80 mg/4 mL, 200 mg/10 mL, or 400 mg/20 mL for intravenous (IV) infusion. The IV formulation of TCZ was previously reviewed by the Canadian Drug Expert Committee for the treatment of RA and received a recommendation to be listed for adults with moderate to severely active RA who have failed to respond to an adequate trial of both DMARDs and a tumour necrosis factor (TNF) alpha inhibitor. The objective of this review was to evaluate the beneficial and harmful effects of the SC formulation of TCZ at recommended doses alone or in combination with methotrexate (MTX) or other DMARDs in adult patients with moderately to severely active RA with an inadequate response to one or more DMARDs and/or TNF alpha inhibitor therapies.
25964853 Reversible methotrexate-associated lymphoma of the liver in rheumatoid arthritis: a unique 2015 Primary hepatic lymphoma (PHL) is an extremely rare disease, frequently associated with viruses such as hepatitis B virus (HBV), hepatitis C virus (HCV), and human immune deficiency virus (HIV). On the other hand, an increased risk of lymphoproliferative disorders (LPD) has been demonstrated in patients treated with immunosuppressive drugs such as methotrexate (MTX) for rheumatoid arthritis (RA). The role of Epstein-Barr virus (EBV) has been discussed in the pathogenesis of the immunodeficiency-associated LPDs. We here describe a RA patient, who developed PHL during RA treatment. The patient was a 64 year-old Japanese male with a 2-year history of RA, who had been treated with MTX at weekly dose of 8-14 mg for 2 years and infliximab (IFX) for 7 months. He presented with a 2 month history of generalized malaise, right hypochondrium pain and fever. Contrast-enhanced computed tomography (CECT) of the abdomen showed multiple irregular and nodular liver masses with a maximum of 13 cm in diameter on the right liver. Biopsy specimens demonstrated CD20-positve diffuse large B-cell lymphoma (DLBCL), but EBV was not identified by EBV-encoded RNA in situ hybridization. Serology for HBV, HCV, human T-cell leukemia virus I (HTLV-I), and HIV was negative. His symptoms disappeared following discontinuation of RA treatment including MTX. A drastic regression of the tumor masses was further obtained without cytotoxic chemotherapy. In addition, although the patient had no past history of liver dysfunction before MTX therapy, persistent elevation of liver enzymes has been observed during MTX treatment. These findings show a causative role of MTX in the development of reversible PHL in the patient.
25653545 Economic evaluation of anti-TNF agents for patients with rheumatoid arthritis in Greece. 2015 OBJECTIVES: We aimed to estimate the total mean annual treatment cost of different therapy options for patients with moderate-to-severe rheumatoid arthritis (RA) in Greece. METHODS: A cost-minimization approach was adopted. An economic model was developed to estimate the direct costs of the three widely used treatments within a 1-year time horizon, from a health care payer perspective, either for new or for existing patients. Data on resource use, dose escalation, and frequency of therapy were based on a nationwide field survey of rheumatologists. Other analyses were also undertaken based on evidence from the literature. Total cost comprised the cost of drugs, administration, and hospital day care visits. Unit cost data were obtained from the price bulletin and the government gazettes issued by the Ministry of Health. Due to the short time horizon of the study, the cost was not discounted. RESULTS: The mean annual total cost per new (or per existing) responder patient on etanercept was estimated at €9,845 (€9,840), and the total cost on etanercept/methotrexate (MTX) was estimated at €9,857 (€9,852). Therapy with etanercept had lower annual cost relative to adalimumab and infliximab. On an annual basis, it was estimated that the difference between etanercept monotherapy and adalimumab monotherapy was €544 (€1,323). Similarly, the difference between etanercept/MTX and infliximab/MTX was €1,871 (€1,490) and €543 (€1,323), respectively, relative to adalimumab/MTX. Results remained constant under other scenario analyses undertaken. CONCLUSION: In the real-life practice setting in Greece, where dose intensity and frequency differences occur, etanercept alone or in combination with MTX, if prescribed as per label, represents the option with lower annual cost per patient when compared with adalimumab or infliximab in patients with RA. These results hold true as long as the assumptions and data used in the analysis remain stable and may alter if any of the underlying parameters, such as drug price, change.
26824819 [Use of biological therapy in patients with rheumatoid arthritis in the Republic of Kazakh 2015 AIM: To evaluate the clinical efficacy and safety of infliximab (IFM) in patients with rheumatoid arthritis (RA). SUBJECTS AND METHODS: Twelve inpatients (10 women and 2 men) aged 23 to 65 years with a valid diagnosis of RA, the duration of which was 3 years or more, were retrospectively analyzed. DAS28 for RA corresponded to grades II and III in 4 (33.3%) and 8 (66.7%) patients, respectively. Long before the investigation, all the patients used methotrexate in a weekly dose of 15 mg and nonsteroidal anti-inflammatory drugs; 6 patients received methipred in a daily dose of 4-8 mg. IFM was administered intravenously dropwise on the basis of 3 mg/kg weight in 250 ml of isotonic sodium hydrochloride solution during 2 hours at 0, 2, and 6 weeks after therapy initiation and then every 8 weeks. RESULTS: During combination therapy after the first IFM infusion, all the 12 patients were noted to have a positive clinical effect as a significant reduction in the number of tender joints and swollen joints, morning stiffness, erythrocyte sedimentation rate, C-reactive protein, regression of the clinical manifestations of the disease, and its laboratory activity. The therapy was tolerated well by all the patients. According to the EULAR criteria, a good therapeutic effect was observed in 10 (83%) patients and clinical remission was achieved in 2 (17%) patients. According to the ACR criteria, 50 and 70% improvement was seen in 1 (8%) and 9 (75%) patients, respectively. Two (17%) patients achieved remission. CONCLUSION: Combination therapy with IFM and MT for RA is highly effective, suppresses disease inflammatory activity and joint destruction; furthermore, there may be remission induction.
25981388 Prevention of stroke in rheumatoid arthritis. 2015 Jul Recognizing that systemic inflammation is a major contributor to the increased risk of cardiovascular disease (CVD), including stroke, in rheumatoid arthritis (RA) serves as the basis for prevention strategies for cerebrovascular disease in RA. In addition to traditional cardiovascular risk factors, recognize that RA may be an independent risk factor for cerebrovascular accident (CVA). The risk of CVD should be assessed in each patient with RA, utilizing modified risk score calculators. Careful monitoring and control of systemic inflammation should be undertaken in conjunction with assessing each patient's CVD risk, acknowledging the benefits and risks of specific RA-directed therapies. Emphasis should be given to early and aggressive control of inflammation in RA patients, particularly those with seropositivity, increased inflammatory markers, long disease duration (>10 years), and/or extra-articular manifestations. In RA patients requiring glucocorticoid therapy, attempts should be made to use or wean to the minimal effective dose (preferably less than 7.5 mg/day). It should be recognized that both disease-modifying antirheumatic drugs (DMARDs), particularly methotrexate, and tumor necrosis factor (TNF)-alpha inhibitors partially mitigate the risk of CVD. In patients with inadequate control of inflammation with DMARDs, consideration should be given to switch to anti-TNF agents earlier in the disease process. Modifiable risk factors should be addressed as per guidelines for the general population. Active RA may be considered as a risk equivalent to diabetes mellitus when applying these guidelines. With regard to lipid management and use of statin therapy, further studies are required given the apparent "lipid paradox" in RA. Use of aspirin for primary prevention in RA has not been well studied; however, when aspirin is used for secondary prevention, one should recognize that concomitant use of nonsteroidal anti-inflammatory drugs (NSAIDs) may decrease the antiplatelet effect. Given the cardiovascular risk associated with NSAIDs, the lowest possible dose for the shortest time should be used.
27980801 Genetic polymorphisms of enzyme proteins and transporters related to methotrexate response 2016 BACKGROUND: Methotrexate (MTX) is currently the anchor drug widely used worldwide in the treatment of rheumatoid arthritis (RA). However, the therapeutic response to MTX has been shown to vary widely among individuals, genders and ethnic groups. The reason for this has been not clarified but it is considered to be partially due to several mechanisms in the cellular pathway of MTX including single-nucleotide polymorphisms (SNPs). The purpose of this study was to investigate the allelic frequencies in different ethnic and/or population groups in the 10 polymorphisms of enzyme proteins and transporters related to the MTX response and pharmacokinetics including MTHFR, TYMS, RFC1, FPGS, GGH, ABCB1, ABCC2 and ABCG2 in unrelated healthy Japanese adults and patients with RA. METHODS: Ten polymorphisms, methylenetetrahydrofolate reductase (MTHFR) 1298, thymidylate synthase (TYMS) 3'-UTR, reduced folate carrier 1 (RFC1) 80 and-43, folypolyglutamyl synthase (FPGS) 1994, γ-glutamyl hydrolase (GGH) 452 and-401, the ABC transporters (ABCB1 3435, ABCC2 IVS23 + 56, ABCG2 914) of enzyme proteins and transporters related to MTX response and pharmacokinetics in 299 unrelated healthy Japanese adults and 159 Japanese patients with RA were investigated to clarify their contributions to individual variations in response and safety to MTX and establish personalized MTX therapy. SNPs were evaluated using real-time polymerase chain reaction (PCR). RESULTS: Comparison of allelic frequencies in our study with other ethnic/population groups of healthy adults and RA patients showed significant differences in 10 polymorphisms among healthy adults and 7 among RA patients. Allelic frequencies of MTHFR 1298 C, FPGS 1994A and ABCB1 3435 T were lower in Japanese than in Caucasian populations and those of ABCC2 IVS23 + 56 C and ABCG2 914A were higher in Japanese than in Caucasian/European populations in both healthy adults and RA patients. Allelic frequencies of MTHFR 1298 C, GGH-401 T, ABCB1 3435 T, and ABCG2 914A were higher in healthy Japanese adults than in an African population, and those of RFC1 80A, RFC1-43C and ABCC2 IVS23 + 56 C in healthy Japanese adults were lower than in Africans. However, no significant differences were seen in the distribution of allelic frequencies between healthy Japanese adults and RA patients. CONCLUSION: The variations in allelic frequencies in different ethnic and/or population groups in healthy adults and RA patients may contribute to individual variations in MTX response and toxicity.
26939782 Difficult-To-Treat Juvenile Idiopathic Arthritis: Current and Future Options. 2016 Apr Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic disease in childhood and is usually treated with non-steroidal anti-inflammatory drugs or disease-modifying anti-rheumatic drugs (DMARDs) such as methotrexate or sulfasalazine. However, not all patients respond to these treatments, and toxicities may limit long-term use or diminish compliance. With advances in pharmacotherapy and the development of new therapeutic agents, there have been improvements in treatment of both systemic and non-systemic JIA, particularly with biologic agents such as anti-tumor necrosis factor (TNF)-α, anti-interleukin (IL)-1, and anti-IL6. Anti-cell therapies, such as co-stimulator blockers or anti-CD20, small molecules, and biosimilars represent new areas of interest, and, while many are not yet currently commercially available for use in children, preliminary studies appear to be promising. In the present article, the authors review therapeutic strategies for the different JIA subtypes, mainly according to guidelines and recommendations. Newer and possible future treatments for arthritis, already approved in adults but currently under study in children, are also discussed. Drugs currently in development plans for rheumatoid arthritis, which hopefully will also be useful for JIA patients in the future, are also mentioned in this paper.
26524897 [Roles of Musculoskeletal Ultrasonography in the Management of Rheumatic Diseases]. 2015 May Inflammation of soft tissues and the subsequent structural damage are the characteristic features of many rheumatic conditions. However, the conventional measures to evaluate these features are not accurate, potentially causing under- and over-diagnosis or treatment. Musculoskeletal ultrasonography, on the other hand, directly visualizes features which are characteristic to rheumatic conditions, such as synovitis, tenosynovitis, bursitis, enthesitis, crystal depositions, bone erosions, and osteophytes/enthesophytes. By visualizing these key features, ultrasound facilitates a more accurate evaluation of rheumatic diseases such as rheumatoid arthritis (RA), spondyloarthropathy, crystal-induced arthritis, and osteoarthritis. For RA, we investigated the impact of ultrasound on the 2010 ACR/EULAR RA classification criteria when joint involvement was determined. We assessed 109 patients with early arthritis using ultrasound. When the presence of joint swelling and number of involved joints were determined by ultrasound, the classification of RA was different from that without ultrasound in approximately 20% of the patients. Moreover, the accuracy of the classification to identify patients who required methotrexate treatment within a year improved by ultrasound. In addition, we and other investigators demonstrated the advantage of ultrasound over conventional measures in the assessment of disease activity of RA. Ultrasound also supports the education of both physicians and patients and communication between them. The utilization of musculoskeletal ultrasonography in more hospitals and clinics is expected to improve the quality of daily practice for rheumatic diseases.
26028960 Biologic monotherapy in the treatment of rheumatoid arthritis. 2015 Biologics, possibly in combination with a conventional disease-modifying antirheumatic drug (DMARD) - preferably methotrexate (MTX), are used in accordance with the recommendations of the international rheumatological societies. However, in clinical practice, this recommendation is often problematic, as many rheumatologists know from personal experience. The quality of life of the patient is affected mainly by drug-induced intolerances (eg, MTX). Thus, the acceptance of the patient to treatment is often so inadequate that a discontinuation of the drug is necessary. In daily practice, approximately 30% of patients with biological therapy receive no concomitant DMARD according to the register data.
26483672 CD5-Positive Primary Intraocular B-Cell Lymphoma Arising during Methotrexate and Tumor Nec 2015 Sep PURPOSE: To report a case of CD5+ primary intraocular B-cell lymphoma arising during methotrexate (MTX) and tumor necrosis factor (TNF) inhibitor treatment in a young patient with rheumatoid arthritis and uveitis. CASE PRESENTATION: A 39-year-old woman treated with MTX and a TNF inhibitor for rheumatoid arthritis and uveitis had steroid-resistant vitreous opacity. A vitreous sample was obtained by using diagnostic vitrectomy and was categorized as class V based on cytologic examination. Flow cytometric analysis of the vitreous sample revealed that abnormal cells were CD5+, CD10-, CD19+, CD20+ and immunoglobulin light-chain kappa+, suggesting the diagnosis of CD5+ primary intraocular B-cell lymphoma. Polymerase chain reaction (PCR) detected immunoglobulin heavy-chain gene rearrangement. Epstein-Barr virus (EBV) DNA was detected in the vitreous sample by using PCR, and immunohistochemistry revealed EBV latent membrane protein-1 expression in the abnormal cells infiltrating the vitreous. Optic nerve invasion was observed on magnetic resonance imaging. CONCLUSION: Primary intraocular lymphoma (PIOL) may develop in patients receiving MTX and TNF inhibitor treatment. EBV infection may play an important role in the pathogenesis of PIOL arising during immunosuppressive therapy.
26061056 Rheumatic Manifestations in Patients with Chikungunya Infection. 2015 Jun Chikungunya virus (CHIKV) infection is a common cause of febrile arthritis. The most common manifestations of acute infection are fever, symmetrical polyarthralgias or polyarthritis, myalgias, and maculopapular rash. Up to 80% of patients may develop musculoskeletal manifestations that persist longer than 3 months, causing impairment in their quality of life. The most common chronic manifestations are persistent or relapsing-remitting polyarthralgias, polyarthritis, and myalgias. Fingers, wrists, knees, ankles, and toes are the most frequently involved, but proximal joints and axial involvement can occur in the chronic stage. Chronic manifestations of CHIKV infection may resemble those of some autoimmune connective tissue diseases. Furthermore, CHIKV infection can cause cryoglobulinemia and may induce rheumatoid arthritis and seronegative spondyloarthropathies in genetically susceptible individuals. The Centers for Disease Control and Prevention recommend acetaminophen and non steroidal anti-inflammatory drugs for the acute rheumatic manifestations of CHIKV infection. However, some studies suggest that low-dose corticosteroids for about 1-2 months (depending on clinical course) are beneficial in relieving acute rheumatic symptoms. Conversely, hydroxychloroquine in combination with corticosteroids or other disease modifying anti-rheumatic drugs (DMARDs) has been successful in treating chronic rheumatic manifestations. Methotrexate and sulfasalazine (alone or in combination) have also been effective for chronic CHIKV arthritis. Patients with CHIKV infection should be closely monitored to identify those with chronic arthritis who would benefit from a rheumatologic evaluation and early treatment with DMARDs.
26523061 Disease-modifying Antirheumatic Drugs (DMARD) and Combination Therapy of Conventional DMAR 2015 Nov Treatment with nonsteroidal antiinflammatory drugs (NSAID) is the recommended first-line therapy in patients with axial spondyloarthritis (axSpA); and for those patients who have persistently active disease, the introduction of tumor necrosis factor-α (TNF-α) inhibitors is indicated. Conventional nonbiological disease-modifying antirheumatic drugs (DMARD), although effective and used in clinical practice for peripheral arthritis, are not recommended. Few studies have been conducted with the aim of evaluating the effect of conventional DMARD, either alone or in combination, in axSpA. As for psoriatic arthritis (PsA), DMARD are widely used, but few trials are available about their effects on axial involvement, which is not often assessed as a primary outcome in clinical trials. In rheumatoid arthritis, combination therapy of 2 or more conventional DMARD appears to confer better response than methotrexate monotherapy, and may even be a viable alternative to TNF-α inhibitors. In peripheral PsA, combination therapy can be used after treatment failure with 1 DMARD, but few studies have been conducted. However, available evidence for the combination of conventional DMARD indicates a lack of any significant benefit on axial symptoms; thus this treatment approach does not represent an effective alternative to anti-TNF-α therapy.
26273164 Erythrodermic Psoriasis Treated with Golimumab: A Case Report. 2015 Aug Erythrodermic psoriasis (EP) is a very severe variant of psoriasis whose management poses a challenge to physicians, as currently available therapies often provide unsatisfactory results. Many biologics have been used to treat chronic plaque psoriasis, the most common form of psoriasis; however, their effectiveness for EP is poorly understood. A recently developed biologic, golimumab, has been extensively studied for the treatment of moderate-to-severe active rheumatoid arthritis, psoriatic arthritis, active ankylosing spondylitis, and chronic plaque psoriasis. However, no clinical trials have been performed for EP. Here, we report the case of a 32-year-old man who presented with severe psoriasis that previously failed to respond satisfactorily to methotrexate, cyclosporine, retinoid, narrow-band ultraviolet B phototherapy, and topical agents (i.e., steroids and calcipotriol). Skin lesions worsened progressively and developed into erythroderma. Psoriatic arthritis was also detected. Conventional therapies lacked efficacy. Therefore, we administered golimumab 50 mg. The skin lesions improved significantly according to the Psoriasis Area and Severity Index score after the first administration; lesions improved further throughout the treatment course. Although additional studies are required to fully evaluate the efficacy and safety of golimumab, this agent may be an alternative treatment strategy for some patients with recalcitrant EP.
26549204 Clinical effectiveness of CT-P13 (Infliximab biosimilar) used as a switch from Remicade (i 2015 OBJECTIVE: To gain clinical experience on the effectiveness and safety of switching from infliximab-Remicade(INX) to infliximab-biosimilar-CT-P13(INB) in patients with established rheumatic disease. METHODS: Patients receiving INX treatment at a rheumatology clinic consented to switching from INX to INB. Patient reported outcomes (PROs), disease-activity, and inflammatory markers were recorded at every visit. Generalized estimating equation models and time-dependent area under the curve (AUC) before/during INX and INB treatments were employed. RESULTS: Thirty-nine consecutive patients [mean (SD) age 53 (11), 17 F] with various rheumatic diseases were switched to INB after a mean (SD) of 4.1 (2.3) years on INX. Thirty-one patients were on concomitant methotrexate. At a median (range) of 11 (7.5-13) months following the first administration of INB, AUCs for disease activity and PROs were similar for INX and INB. They were better compared to those prior to INX. Eleven patients (28.2%) discontinued INB, due to INX antidrug antibodies detected prior to INB infusion (n = 3); latent tuberculosis (n = 1); new-onset neurofibromatosis (n = 1); subjective reasons with no objective deterioration of disease (n = 6). CONCLUSION: The clinical effectiveness of INB in both PROs and disease-activity measures was comparable to INX during the first year of switching, with no immediate safety signals. Subjective reasons (negative expectations) may play a role among discontinuations of biosimilars. Larger patient numbers and longer follow-up are necessary for confirming this clinical experience.
26172530 Effects of methotrexate and salazosulfapyridine on protein profiles of exosomes derived fr 2016 Feb PURPOSE: To elucidate effects of salazosulfapyridine (SASP) and methotrexate (MTX), major anti-rheumatic drugs, on exosomes derived from SW982 of a human synovial sarcoma cell line. EXPERIMENTAL DESIGN: SW982 was treated with SASP and/or MTX under interleukin-1β (IL-1β)-treated or nontreated conditions. Exosomes were isolated from the culture media, and exosomal proteome was analyzed by 2D-DIGE. Protein spots whose intensity was significantly altered by the above treatments were identified by MS. RESULTS: Two hundred ninety-four protein spots were detected in the exosome preparations by 2D-DIGE. Compared to the nontreated cells, SASP-, MTX-, and (SASP + MTX)-treated cells displayed 8, 10, and 21 exosomal protein spots with more than ±2.0-fold intensity differences (p < 0.05), respectively. Similarly, the IL-1β-treated cells displayed 58 exosomal protein spots with more than ±1.5-fold intensity differences (p < 0.05). In about half of the 58 spots, the IL-1β-induced intensity changes were suppressed by simultaneous addition of SASP and/or MTX. Most of the identified proteins were immunity- or anti-oxidation-related proteins. CONCLUSIONS AND CLINICAL RELEVANCE: The SASP and/or MTX treatments altered the protein profiles of exosomes and suppressed the effects of IL-1β on the exosomal proteome. Exosomes may play roles in the actions of these anti-rheumatic drugs.
27461230 From the Medical Board of the National Psoriasis Foundation: Perioperative management of s 2016 Oct Treatment with systemic immunomodulatory agents is indicated for patients with moderate to severe plaque psoriasis and psoriatic arthritis. In these patients, surgery may confer an increased risk of infectious or surgical complications. We conducted a literature review to examine studies addressing the use of methotrexate, cyclosporine, and targeted immunomodulatory agents (tumor necrosis factor-alfa inhibitors, interleukin [IL]-12/23 inhibitors, IL-17 inhibitors) in patients undergoing surgery. We examined 46 total studies; the majority were retrospective studies in patients with rheumatoid arthritis and inflammatory bowel disease. One study in patients with psoriasis and psoriatic arthritis reviewed 77 procedures and did not find an elevated risk of postoperative complications with tumor necrosis factor-alfa and IL-12/23 inhibitors even with major surgeries. Based on level III evidence, infliximab, adalimumab, etanercept, methotrexate, and cyclosporine can be safely continued through low-risk operations in patients with psoriasis and psoriatic arthritis. For moderate- and high-risk surgeries, a case-by-case approach should be taken based on the patient's individual risk factors and comorbidities.
25853338 Treatment of Collagen-Induced Arthritis Using Immune Modulatory Properties of Human Mesenc 2016 Mesenchymal stem cells (MSCs) have immune modulatory properties. We investigated the potential therapeutic effects of human bone marrow (BM)-, adipose tissue (AD)-, and cord blood (CB)-derived MSCs in an experimental animal model of rheumatoid arthritis (RA) and explored the mechanism underlying immune modulation by MSCs. We evaluated the therapeutic effect of clinically available human BM-, AD-, and CB-derived MSCs in DBA/1 mice with collagen-induced arthritis (CIA). CIA mice were injected intraperitoneally with three types of MSCs. Treatment control animals were injected with 35 mg/kg methotrexate (MTX) twice weekly. Clinical activity in CIA mice, degree of inflammation, cytokine expression in the joint, serum cytokine levels, and regulatory T cells (Tregs) were evaluated. Mice treated with human BM-, AD-, and CB-MSCs showed significant improvement in clinical joint score, comparable to MTX-treated mice. Histologic examination showed greatly reduced joint inflammation and damage in MSC-treated mice compared with untreated mice. Microcomputed tomography also showed little joint damage in the MSC-treated group. MSCs significantly decreased serum interleukin (IL)-1β, tumor necrosis factor (TNF)-α, IL-6, and interferon-γ and increased IL-10 and transforming growth factor-β levels. Tregs were increased in mice treated with MSCs compared to untreated or MTX-treated mice. Human BM-, AD-, and CB-MSCs significantly suppressed joint inflammation in CIA mice. The cells decreased proinflammatory cytokines and upregulated anti-inflammatory cytokines and induced Tregs. Therefore, our study suggests that the use of human BM-, AD-, and CB-MSCs could be an effective therapeutic approach for RA.