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ID PMID Title PublicationDate abstract
26420575 Long noncoding RNAs could be potential key players in the pathophysiology of Sjögren's sy 2015 Nov Long noncoding RNAs (lncRNAs) are a recently discovered class of noncoding functional RNAs encoded by metazoan genomes. Recent studies suggest a larger regulatory role for lncRNAs in critical biological and disease processes. Mounting evidence on the role of lncRNAs in regulating key processes of the immune system prompted us to hypothesize the role of lncRNAs as key regulators of the pathophysiology of Sjögren's syndrome (SS). We used two similar approaches based on reanalysis of microarray expression datasets and curation of lncRNA-protein coding gene interactions from literature to derive support for our hypothesis. We also discuss potential caveats to our approach and suggest approaches to validate the hypothesis. Our analysis suggests the potential larger and hitherto unknown role of lncRNA regulatory networks in modulating the expression of key genes involved in the pathogenesis of SS and thereby modulating the pathophysiology of SS.
27186143 Aryl hydrocarbon receptor antagonism and its role in rheumatoid arthritis. 2015 Although rheumatoid arthritis (RA) is the most common autoimmune disease, affecting approximately 1% of the population worldwide, its pathogenic mechanisms are poorly understood. Tobacco smoke, an environmental risk factor for RA, contains several ligands of aryl hydrocarbon receptor (Ahr), also known as dioxin receptor. Ahr plays critical roles in the immune system. We previously demonstrated that Ahr in helper T-cells contributes to development of collagen-induced arthritis, a mouse model of RA. Other studies have shown that cigarette smoke condensate and pure Ahr ligands exacerbate RA by altering bone metabolism and inducing proinflammatory responses in fibroblast-like synoviocytes. Consistent with these findings, several Ahr antagonists such as α-naphthoflavone, resveratrol, and GNF351 reverse the effect of Ahr ligands in RA pathogenesis. In this review, we summarize the current knowledge of Ahr function in the immune system and the potential clinical benefits of Ahr antagonism in treating RA.
26742190 Pleural Effusion In A Patient With Primary Sjögren's Syndrome Successfully Treated With C 2015 Jul Sjögren's syndrome is a systemic autoimmune disorder characterized by salivary insufficiency and lymphocytic infiltration of the exocrine glands. Bronchiolitis and bronchiectasis are common airway manifestations but interstitial pneumonitis, and lymphocytic interstitial pneumonitis may also occur. It rarely presents with pleuritis. We report a woman with primary Sjögren's syndrome who developed pleuritis with moderately large effusions and antibody levels for SS-A and SS-B in the serum without evidence of infection, malignancy or other collagen diseases. After the initial treatment, daily administration of 20 mg of oral prednisone has effectively controlled the serious manifestations of the disease with minimal side effects.
26367089 Sjögren syndrome: what and where are we looking for? 2015 Nov PURPOSE OF REVIEW: Sjögren's syndrome affects exocrine glands leading to a dry mouth and dry eyes. Dry eye manifestations can precede the diagnosis of Sjögren's syndrome by many years. Innumerous spontaneous and inducible Sjögren's syndrome models have been used to study the pathogenesis of Sjögren's syndrome. This review focuses on recent human data, ocular and extraglandular manifestations of animal models, what is known, what is still unknown and how we need to look, and their correlation correspondence to human disease. RECENT FINDINGS: Hallmarks of dry eye in Sjögren's syndrome include increased corneal staining, goblet cell loss and low tear volume. Confocal microscopy and impression cytology are able to clarify new markers of the ocular disease. Extraglandular manifestations should be an alert more severe complications in the eye. Some models have strong sex and exocrine gland predilection, whereas aging generally worsens the disease phenotype. Although most models do not display a significant increase in corneal staining or tear secretion impairment, conjunctival infiltration and decrease in goblet cells are frequently seen. SUMMARY: We have seen great advances in the role of inflammation in ocular, oral and extra-glandular manifestations of Sjögren's syndrome. Several mechanisms and mediators of Sjögren's syndrome have been elucidated in animal model studies.
27933206 Improving inflammatory arthritis management through tighter monitoring of patients and the 2016 Treating to target by monitoring disease activity and adjusting therapy to attain remission or low disease activity has been shown to lead to improved outcomes in chronic rheumatic diseases such as rheumatoid arthritis and spondyloarthritis. Patient-reported outcomes, used in conjunction with clinical measures, add an important perspective of disease activity as perceived by the patient. Several validated PROs are available for inflammatory arthritis, and advances in electronic patient monitoring tools are helping patients with chronic diseases to self-monitor and assess their symptoms and health. Frequent patient monitoring could potentially lead to the early identification of disease flares or adverse events, early intervention for patients who may require treatment adaptation, and possibly reduced appointment frequency for those with stable disease. A literature search was conducted to evaluate the potential role of patient self-monitoring and innovative monitoring of tools in optimising disease control in inflammatory arthritis. Experience from the treatment of congestive heart failure, diabetes and hypertension shows improved outcomes with remote electronic self-monitoring by patients. In inflammatory arthritis, electronic self-monitoring has been shown to be feasible in patients despite manual disability and to be acceptable to older patients. Patients' self-assessment of disease activity using such methods correlates well with disease activity assessed by rheumatologists. This review also describes several remote monitoring tools that are being developed and used in inflammatory arthritis, offering the potential to improve disease management and reduce pressure on specialists.
27703452 Anti-rheumatoid Activity of Secondary Metabolites Produced by Endophytic Chaetomium globos 2016 The aim of the present study was to investigate the anti-rheumatoid activity of secondary metabolites produced by endophytic mycobiota in Egypt. A total of 27 endophytic fungi were isolated from 10 dominant medicinal plant host species in Wadi Tala, Saint Katherine Protectorate, arid Sinai, Egypt. Of those taxa, seven isolates of Chaetomium globosum (CG1-CG7), being the most frequent taxon, were recovered from seven different host plants and screened for production of active anti-inflammatory metabolites. Isolates were cultivated on half - strength potato dextrose broth for 21 days at 28°C on a rotatory shaker at 180 rpm, and extracted in ethyl acetate and methanol, respectively. The probable inhibitory effects of both extracts against an adjuvant induced arthritis (AIA) rat model were examined and compared with the effects of methotrexate (MTX) as a standard disease-modifying anti-rheumatoid drug. Disease activity and mobility scoring of AIA, histopathology and transmission electron microscopy (TEM) were used to evaluate probable inhibitory roles. A significant reduction (P < 0.05) in the severity of arthritis was observed in both the methanolic extract of CG6 (MCG6) and MTX treatment groups 6 days after treatment commenced. The average arthritis score of the MCG6 treatment group was (10.7 ± 0.82) compared to (13.8 ± 0.98) in the positive control group. The mobility score of the MCG6 treatment group (1.50 ± 0.55) was significantly lower than that of the positive control group (3.33 ± 0.82). In contrast, the ethyl acetate extract of CG6 (EACG6) treatment group showed no improvements in arthritis and mobility scores in AIA model rats. Histopathology and TEM findings confirmed the observation. Isolate CG6 was subjected to sequencing for confirmation of phenotypic identification. The internal transcribed spacer (ITS) 1-5.8 s - ITS2 rDNA sequences obtained were compared with those deposited in the GenBank Database and registered with accession number KC811080 in the NCBI Database. The present study revealed that the methanol extract of endophytic fungus C. globosum (KC811080) recovered from maidenhair fern has an inhibitory effect on inflammation, histopathology and morphological features of rheumatoid arthritis in an AIA rat model.
26255767 [Tuberculous rheumatism "Poncet's disease". Case report]. 2016 Mar BACKGROUND: Deaths due to tuberculosis have reached 2.5 million cases per year worldwide. Poncet's disease is an infrequent form of tuberculosis characterised by a clinical picture of polyarthritis. CLINICAL CASE: A 24-year-old male presented with morning stiffness, arthralgias, bilateral symmetric arthritis of the proximal interphalangeal joints, wrists, knees, ankles, and shoulders, and adenomegalies at the cervical, submandibular, left supraclavicular, axillary and inguinal levels, without fever. Laboratory results were as follows: ESR 44mm/h, C-reactive protein 4.35, normal levels of complement C3 and C4, negative rheumatoid factor and anticyclic citrullinated peptide antibodies, positive antinuclear antibodies with fine speckled pattern (1:320) and cytoplasm (1:160) pattern and negative anti-Smith, -double-stranded DNA, Sjogren's syndrome-antigen A and Sjogren's syndrome-antigen B. Histological report of cervical node tissue revealed granulomatous lesions compatible with tuberculosis. Rheumatoid arthritis and systemic lupus erythematosus were ruled out. Anti-tuberculosis agents were initiated that resolved the clinical picture. Diagnosis of Poncet's disease was confirmed. CONCLUSION: The differential diagnosis between tuberculosis and autoimmune inflammatory joint diseases is a clinical challenge.
26579954 Chemically Modified Interleukin-6 Aptamer Inhibits Development of Collagen-Induced Arthrit 2016 Feb Interleukin-6 (IL-6) is a potent mediator of inflammatory and immune responses, and a validated target for therapeutic intervention of inflammatory diseases. Previous studies have shown that SL1026, a slow off-rate modified aptamer (SOMAmer) antagonist of IL-6, neutralizes IL-6 signaling in vitro. In the present study, we show that SL1026 delays the onset and reduces the severity of rheumatoid symptoms in a collagen-induced arthritis model in cynomolgus monkeys. SL1026 (1 and 10 mg/kg), administered q.i.d., delayed the progression of arthritis and the concomitant increase in serum IL-6 levels compared to the untreated control group. Furthermore, SL1026 inhibited IL-6-induced STAT3 phosphorylation ex vivo in T lymphocytes from human blood and IL-6-induced C-reactive protein and serum amyloid A production in human primary hepatocytes. Importantly, SOMAmer treatment did not elicit an immune response, as evidenced by the absence of anti-SOMAmer antibodies in plasma of treated monkeys. These results demonstrate that SOMAmer antagonists of IL-6 may be attractive agents for the treatment of IL-6-mediated diseases, including rheumatoid arthritis.
27590658 Incidence of autoimmune diseases in a nationwide HIV/AIDS patient cohort in Taiwan, 2000-2 2017 Apr OBJECTIVES: It is not known if the incidences of autoimmune diseases are higher in individuals living with HIV infection or AIDS. Our study investigated the incidences of autoimmune diseases among people living with HIV/AIDS (PLWHA) in Taiwan during 2000-2012. METHODS: The Taiwan National Health Insurance Research Database was used to identify PLWHA. The incidence densities of systemic and organ-specific autoimmune diseases were calculated, and age-adjusted, sex-adjusted and period-adjusted standardised incidence rates (SIRs) were obtained by using two million people from the general population as controls. To examine the effects of highly active antiretroviral therapy (HAART) on the incidence of autoimmune diseases, the incidence densities and SIRs of autoimmune diseases were calculated after stratifying PLWHA by HAART status. RESULTS: Of the 20 444 PLWHA identified, the overall mean (SD) age was 30.1 (11.0) years; 67.2% of the subjects received HAART. As compared with the general population, SIRs were higher for incident Sjögren syndrome (SIR=1.64; 95% CI 1.24 to 2.13), psoriasis (SIR=2.05; 95% CI 1.67 to 2.48), systemic lupus erythematosus (SLE) (SIR=2.59; 95% CI 1.53 to 4.09), autoimmune haemolytic anaemia (SIR=35.06; 95% CI 23.1 to 51.02) and uveitis (SIR=2.50; 95% CI 2.05 to 3.02), but were lower for incident ankylosing spondyloarthritis (SIR=0.70; 95% CI 0.48 to 0.99). When the effect of HAART on incident autoimmune diseases was considered, PLWHA who received HAART had higher SIRs for psoriasis, autoimmune haemolytic anaemia and uveitis, but had lower risks of rheumatoid arthritis (RA) and ankylosing spondyloarthritis. In contrast, PLWHA who did not receive HAART had higher SIRs for Sjögren syndrome, psoriasis, RA, SLE, scleroderma, polymyositis, autoimmune haemolytic anaemia and Hashimoto's thyroiditis. CONCLUSIONS: PLWHA had higher risks of incident Sjögren syndrome, psoriasis, SLE, autoimmune haemolytic anaemia and uveitis.
27293517 Efficacy of Mitochondrial Antioxidant Plastoquinonyl-decyl-triphenylphosphonium Bromide (S 2016 Rheumatoid arthritis is one of the most common autoimmune diseases. Many antioxidants have been tested in arthritis, but their efficacy was, at best, marginal. In this study, a novel mitochondria-targeted antioxidant, plastoquinonyl-decyl-triphenylphosphonium bromide (SkQ1), was tested in vivo to prevent and cure experimental autoimmune arthritis. In conventional Wistar rats, SkQ1 completely prevented the development of clinical signs of arthritis if administered with food before induction. Further, SkQ1 significantly reduced the fraction of animals that developed clinical signs of arthritis and severity of pathological lesions if administration began immediately after induction of arthritis or at the onset of first symptoms (day 14 after induction). In specific pathogen-free Wistar rats, SkQ1 administered via gavage after induction of arthritis did not reduce the fraction of animals with arthritis but decreased the severity of lesions upon pathology examination in a dose-dependent manner. Efficacious doses of SkQ1 were in the range of 0.25-1.25 nmol/kg/day (0.13-0.7 μg/kg/day), which is much lower than doses commonly used for conventional antioxidants. SkQ1 promoted apoptosis of neutrophils in vitro, which may be one of the mechanisms underlying its pharmacological activity. Considering its low toxicity and the wide therapeutic window, SkQ1 may be a valuable additional therapy for rheumatoid arthritis.
26523047 Toward Treating to Target in Psoriatic Arthritis. 2015 Nov The concept "treat to target" in rheumatology was first developed for rheumatoid arthritis. A similar attempt to develop such an approach for spondyloarthritis was unsuccessful because the assessment tools and target of therapy had not been developed. In psoriatic arthritis (PsA), composite indices to assess disease activity, disease state, and responsiveness have been developed and can be used as targets. There are a number of definitions for remission, but none are widely accepted. However, a state of minimal disease activity has been defined. There is evidence now that the treat-to-target approach is feasible, using the minimal disease activity state as a target and devising a tight control approach, which is superior to standard of care. Further work will determine the best target and the best approach to reach it.
26471860 Peripheral joint involvement in psoriatic arthritis patients. 2015 Sep Peripheral joint involvement is a common, potentially debilitating feature of psoriatic arthritis (PsA). Joint involvement is commonly symmetrical and polyarticular similar to rheumatoid arthritis (RA) but it can also be oligoarticular, asymmetrical or occasionally monoarticular. Involvement of the distal interphalangeal joints is a feature which distinguishes PsA from RA. Articular involvement in PsA can be severe with a mutilating arthropathy found in about 5%. These patients are characterised clinically by digital shortening and on radiographs by erosion on both sides of the joint and/or osteolysis. Treatments targeting joint disease frequently reduces symptoms and signs resulting in prevention of damage progression.
27688439 Significance of Anti-cyclic Citrullinated Peptide Autoantibodies in Immune-mediated Inflam 2016 Sep BACKGROUND: Anti-cyclic citrullinated peptides (CCPs) are autoantibodies directed against citrullinated peptides. Rheumatoid factor (RF), an antibody against the Fc portion of IgG, is known to form immune complexes and contribute to the etiopathogenesis of various skin disorders. C-reactive protein (CRP), an acute-phase protein, increases following secretion of interleukin-6 from macrophages and T cells. Anti-CCP, RF, and CRP are well-established immune-markers, their diagnostic potential in immune-mediated skin disorders remains less widely studied. AIMS AND OBJECTIVES: To determine the correlation between anti-CCP, RF, and CRP in immune-mediated inflammatory skin diseases. MATERIALS AND METHODS: About 61 clinically diagnosed cases of various immune-mediated skin diseases (psoriasis [n = 38], connective tissue diseases such as systemic lupus erythematosus and systemic sclerosis [n = 14], and immunobullous disorders including pemphigus vulgaris and pemphigus foliaceus [n = 9]) were included in the study. These patients were subclassified on the basis of presence or absence of arthritis. Arthritis was present in nine cases of psoriasis and seven connective tissue disorder patients. Detection of serum anti-CCP was done using enzyme-linked immunosorbent assay, whereas CRP and RF levels were detected using latex agglutination technique. RESULTS: Of the 61 specimens, 14.75% had elevated serum anti-CCP levels. RF and CRP levels were elevated in 18.03% and 39.34% specimens, respectively. RF was elevated in 13.16% of inflammatory and 42.88% of connective tissue disorders, whereas anti-CCP was raised in 10.53% of inflammatory and 35.71% of connective tissue disorders. CRP positivity was highest in connective tissue disorders (50%), followed by 39.47% in inflammatory and 22.22% in immunobullous conditions. In none of the immunobullous patients, anti-CCP or RF levels were found to be elevated. Association of the presence of arthritis with elevated anti-CCP was found to be statistically significant. CONCLUSIONS: Although anti-CCP, RF, and CRP levels are valuable markers of chronic immune-mediated skin disorders, elaborate studies enrolling a larger number of patients are required to validate these diagnostic markers.
27167420 [Eleven-Year Experience with Total Ankle Arthroplasty]. 2016 PURPOSE OF THE STUDY Total joint replacement is one of the options in surgical treatment of advanced ankle arthritis. It allows the ankle to remain mobile but, unfortunately, it does not provide the same longevity as total knee or hip replacements. Therefore, decisions concerning the kind of treatment are very individual and depend on the clinical status and opinion of each patient. MATERIAL AND METHODS A total of 132 total ankle replacements were carried out in the period from 2004 to 2015. The prostheses used included the Ankle Evolutive System (AES) in 52 patients, Mobility Total Ankle System (DePuy) in 24 patients and, recently, Rebalance Total Ankle Replacement implant in 53 patients. Three patients allergic to metal received the Taric prosthesis. Revision arthroplasty using the Hintegra prosthesis was carried out in four patients. The outcome of arthroplasty was evaluated on the American Orthopaedic Foot and Ankle Society (AOFAS) scoring scale. Indications for total ankle arthroplasty included post-traumatic arthritis in 83 patients, rheumatoid arthritis in 37 and primary arthritis in 12 patients. There were 78 women and 54 men, with an average age of 55.6 years at the time of surgery. RESULTS The average follow-up was 6.1 years (1-11 years). The average AOFAS score of the whole group increased from 33.2 before surgery to 82.5 after it. The primary indication had an important role. Arthroplasty outcomes were poorer in patients with post-traumatic arthritis than in those with rheumatoid arthritis or primary arthritis. In patients with post-traumatic arthritis, the average AOFAS score rose to 78.6 due to restricted motion of the ankle, and some patients continued to have pain when walking. The average AOFAS score in a total of 49 patients who had rheumatoid arthritis or primary arthritis reached a value of 86.4. Post-operative complications were recorded in ten patients (7.6%) in whom part of the wound was healing by second intention. Ossification was also a frequent complication and had to be removed in six patients (4.5%). No early infection was recorded and late infection was treated in three patients. The prosthesis had to be removed and ankle arthrodesis performed in seven patients (5.3%). All had necrosis of the talus with ankle instability. In five, the retrograde nail Medin was used and extensive defects remaining after talar necrosis were filled with massive bone grafts obtained from a bone bank. One patient required tibio-calcaneal arthrodesis with external fixator; surgery in one case involved the use of a Zimmer Trabecular Metal Ankle Fusion Spacer with retrograde nail fixation. The development of cystic radiolucencies adjacent to tibial or talar components presents another post-operative complication. It was recorded mostly in the patients after AES implantation, in whom eight of 52 (15.3%) had these findings. DISCUSSION Total ankle arthroplasty is a complicated surgical procedure potentially associated with various technical problems. The occurrence of complications is indirectly related to the experience of the orthopaedist performing surgery; literature data show that the number of complication decreases with an increased frequency of ankle replacements done. CONCLUSIONS Total ankle arthroplasty, as every orthopaedic surgery, has its advantages and disadvantages. The positive aspects are pain relief and improved mobility of the ankle allowing for physiological gait. However, it shows a lower survivorship rate that the other large joint replacements. A successful outcome depends on the correct indication. The ankle should be stable, the talus without signs of necrosis and valgus or varus deviations of the ankle should not exceed 10 to 15 degrees. KEY WORDS: total ankle arthroplasty, re-implantation, aseptic loosening, retrograde nail, Trabecular Metal spacer, revision arthroplasty.
25994972 In vitro and in vivo antioxidant, cytotoxic, and anti-chronic inflammatory arthritic effec 2016 Jul The toxicity of selenium (Se) as an antioxidant supplement in the treatment of arthritis is debatable. In this study, Dextrin stabilized Se nanoparticles (SeNP) of size 64 nm ± 0.158 were used to explore its effects as a potent antioxidant with reduced toxicity in both in vitro and in vivo. In vitro toxicity of SeNP was determined using cytotoxicity assay. In vitro interactions of SeNP with DNA and protein was established. Subacute toxicity of SeNP was studied. Wistar rats with complete freunds adjuvant induced arthritis were used. Various concentrations of SeNP per kg body weight were fed orally daily upto to 21 days. Arthritic profile based on paw swelling, histopathological changes in joints, blood indices, and antioxidant enzymes level in organs such as liver, kidney, and spleen were investigated. Dextrin-SeNP when interacted with NIH-3T3 cells showed 15% cytotoxicity at 100 µg/mL whereas, bulk Se showed 95% at the same concentration. SeNP at 250 µg/mL showed protective effect on DNA. Interaction of SeNP with BSA showed increase in quenching of BSA fluorescence. SeNP did not show any subacute toxicity at concentration as high as 5 mg/kg b.w. in Wistar rats. SeNP at a concentration of 250 µg/kg b.w. acted as potent anti-inflammatory agent and significantly reduced (p < 0.05) arthritis induced parameters. The enzymatic antioxidant levels in liver, kidney, and spleen were restored significantly (p < 0.05) at 500 µg/kg b.w. while CRP was regained to normal at concentration of 100 µg/kg b.w. concluding SeNP at 500 µg/kg b.w. can be a potential antiarthritic drug supplement. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 104B: 993-1003, 2016.
24395558 Mesenchymal stem cell therapy in proteoglycan induced arthritis. 2015 Apr OBJECTIVES: To explore the immunosuppressive effect and mechanism of action of intraperitoneal (ip) and intra-articular (ia) mesenchymal stem cell (MSC) injection in proteoglycan induced arthritis (PGIA). METHODS: MSC were administered ip or ia after establishment of arthritis. We used serial bioluminescence imaging (BLI) to trace luciferase-transfected MSC. Mice were sacrificed at different time points to examine immunomodulatory changes in blood and secondary lymphoid organs. RESULTS: Both ip and local ia MSC injection resulted in a beneficial clinical and histological effect on established PGIA. BLI showed that MSC ip and ia in arthritic mice are largely retained for several weeks in the peritoneal cavity or injected joint respectively, without signs of migration. Following MSC treatment pathogenic PG-specific IgG2a antibodies in serum decreased. The Th2 cytokine IL-4 was only upregulated in PG-stimulated lymphocytes from spleens in ip treated mice and in lymphocytes from draining lymph nodes in ia treated mice. An increase in production of IL-10 was seen with equal distribution. Although IFN-γ was also elevated, the IFN-γ/IL-4 ratio in MSC treated mice was opposite to the ratio in (untreated) active PGIA. CONCLUSIONS: MSC treatment, both ip and ia, suppresses PGIA, a non-collagen induced arthritis model. MSC are largely retained for weeks in the injection region. MSC treatment induced at the region of injection a deviation of PG-specific immune responses, suggesting a more regulatory phenotype with production of IL-4 and IL-10, but also of IFN-γ, and a systemic decrease of pathogenic PG-specific IgG2a antibodies. These findings underpin the potential of MSC treatment in resistant arthritis.
27747532 Use of Anti-Tumor Necrosis Factor Therapy: A Retrospective Study of Monotherapy and Adhere 2015 Dec INTRODUCTION: This study examined the use of anti-tumor necrosis factor (anti-TNF) monotherapy, adherence with non-biologic disease-modifying anti-rheumatic drugs (nbDMARDs) in patients receiving a combination of anti-TNF therapies and nbDMARDs, and the impact of nbDMARD adherence on anti-TNF persistence among patients with rheumatoid arthritis (RA). METHODS: Patients with RA (aged ≥18 years) from a US commercial health plan with claims for anti-TNFs (2006-2010) were defined as either biologic-naive or -exposed anti-TNF initiators based on previous nbDMARD use. Adherence to nbDMARDs and anti-TNF persistence were estimated. Cox regression estimated the association between nbDMARD adherence and anti-TNF persistence. RESULTS: Among 9764 patients identified (mean age 50.2 years; 78% female), 55% of biologic-naive patients and 49% of previously exposed patients initiated any combination therapy during follow-up. Among biologic-naive combination therapy patients, 53% adhered to nbDMARD therapy <80% of the time while receiving anti-TNF therapies; 33% had <60% adherence. Compared with the most adherent patients, patients adherent to nbDMARDs 20% to 79% of the time were 30% to 20% more likely to discontinue their anti-TNF therapy in the period >90 days after starting the anti-TNF therapy. This relationship was not observed for patients with nbDMARD adherence of <20% (who were less likely to discontinue their anti-TNF therapy during the first 90 days of treatment). CONCLUSION: Almost one-third of patients with RA receiving anti-TNF therapy received it as pure monotherapy. About one-third of combination therapy recipients had <60% adherence to nbDMARDs. Higher nbDMARD adherence may be associated with better anti-TNF persistence after an initial treatment period.
26929019 Efficacy and safety of minodronic acid hydrate in patients with steroid-induced osteoporos 2018 Apr OBJECTIVES: Minodronic acid hydrate, an oral bisphosphonate, has a greater inhibitory effect on bone resorption than do other approved drugs; however, this has been studied only in patients with primary osteoporosis. Here, we administered minodronic acid hydrate to patients with steroid-induced osteoporosis who have been treated with steroids for rheumatoid arthritis or other collagen diseases, and the efficacy and safety of minodronic acid hydrate were prospectively investigated. METHODS: Twenty-five patients treated in our rheumatology clinic received minodronic acid hydrate 1 mg/day. The changes in bone mineral density (BMD) and bone turnover markers were investigated at 3 and 6 months, and adverse events, including the presence or absence of an incident osteoporotic fracture, were examined over a period of 6 months. RESULTS: Percent changes in BMD of the lumbar spine and femur significantly increased. The values of bone turnover markers significantly decreased. There were no patients with a radiographically apparent incident fracture. Adverse events included toothache for which the patient discontinued the treatment and three cases of gastrointestinal disorder that did not lead to discontinuation, and thus minodronic acid hydrate was well tolerated. CONCLUSIONS: Here, we show that minodronic acid hydrate is effectively and safely used for treatment of steroid-induced osteoporosis.
27350791 Squamous cell carcinoma of the rectum: a consequence of immunosuppression resulting from i 2016 Treatment with tumour necrosis factor (TNF) antagonists may lead to enhanced susceptibility to certain malignancies. In particular, an association is seen emerging between TNF antagonists and development of squamous cell carcinomas (SCCs) of the skin (in association with psoriasis), the oral cavity, and in the anogenital areas (possibly related to prior human papilloma virus infection). We present here a case of a 53-year old woman with a history of severe rheumatoid arthritis (RA), most recently treated with the TNF antagonist etanercept plus methotrexate, presented to our service after several months of increasing left pelvis and buttock pain. Evaluation with a computerised tomography (CT)-directed biopsy of a pelvic side wall mass revealed a metastatic SCC. On a fluorodeoxyglucose (FDG) positron-emission tomography (PET) an additional area of uptake was identified in the left posterior rectum corresponding to a 1 cm nodule palpable on digital exam. Colonoscopic biopsy revealed a basaloid SCC of the rectum as the likely primary site. Immunosuppression following TNF antagonist therapy may have given arise to this unrestrained neoplastic growth. It thereby underscores the need for an initial baseline study of risk factors and identification of patients who are at higher risk for development of a malignancy, in order to achieve a diagnosis at an early stage.
26965981 Antibodies to infliximab in Remicade-treated rheumatic patients show identical reactivity 2016 Sep OBJECTIVES: The aim of this study was to determine whether antibodies to infliximab (IFX) in Remicade-treated patients cross-react with the biosimilar CT-P13. METHODS: 250 consecutive patients with rheumatic diseases under Remicade and 77 controls were retrospectively selected for the study. Anti-IFX antibodies at drug through levels were measured in parallel with three different bridging ELISA assays: Promonitor-ANTI-IFX kit, which uses Remicade to detect antibodies, and two more assays that use either Inflectra or Remsima with the same format. Correlation and association between each assay was studied. RESULTS: 50.4% of patients were tested positive with Promonitor-ANTI-IFX. All were antibodies to IFX (ATI)-positive when either Inflectra or Remsima assays were used. In all comparisons positive and negative percentage agreements were 100%, and correlation coefficients were ≥0.995. No differences between rheumatoid arthritis and spondyloarthritis, or between concomitant immunosuppressives, were observed. CONCLUSIONS: Anti-IFX antibodies of Remicade-treated patients cross-react with either Inflectra or Remsima. Although additional epitopes may be present in the biosimilar, results suggest that epitopes influencing the immune response to IFX are also present in the biosimilar. Antibody-positive patients treated with Remicade should not be switched to the biosimilar, since antibodies will interact with the new drug and potentially lead to loss of response. This finding supports the utility for therapeutic drug monitoring before a switching strategy is considered.