Browse

Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
25342996 Use of DMARDs and biologics during pregnancy and lactation in rheumatoid arthritis: what t 2014 Oct Rheumatoid arthritis (RA), a chronic autoimmune inflammatory disease of synovial joints, can lead to chronic pain and structural joint damage, as well as other organ involvement, especially if not adequately controlled. Because it can affect women in their reproductive years, care of pregnant women with RA requires a delicate balance of maintaining disease control while limiting potential toxicity to the fetus and neonate. While most women experience a substantial improvement in disease activity during pregnancy, for some women their RA remains active. It can even manifest itself for the first time during pregnancy or early in the post-partum period. Optimizing disease control prior to conception is key, but utilizing disease-modifying treatments effectively and safely throughout pregnancy and lactation requires open dialogue and shared decision making. This review provides evidence-based recommendations for use of disease-modifying antirheumatic drugs (DMARDs) and biologic response modifiers to guide rheumatologists in their care of pregnant and lactating women with RA and serves as a guide to counsel male patients with RA on family planning decisions.
24729739 Clinical utility of etanercept in the treatment of arthritides in children and adolescents 2014 Juvenile idiopathic arthritis (JIA) is a group of chronic inflammatory diseases affecting approximately 300,000 children and adolescents in the United States of unknown cause. It can affect children from the age of 0 years up to the age of 16 years. The International League of Associations of Rheumatology has defined seven subsets of JIA based on several factors including the number of affected joints and the involvement of other tissues; the prognosis for each affected child also depends on multiple factors including age of onset, number of joints involved, and systemic features. As with rheumatoid arthritis in adults, the goal of therapy is remission and resolution of disease activity; however, as a cure does not seem attainable in the near future, a reasonable goal of therapy is prevention of joint damage, inhibition of inflammation, and a high level of quality of life. Even with available therapies, many children with JIA enter adulthood with persistently active disease, suboptimal function, and impaired quality of life. Methotrexate remains the standard of care for children with JIA; etanercept was approved in 2000 in the United States for the treatment of JIA resistant to methotrexate. The efficacy and safety of etanercept therapy in children with JIA is reviewed and its place in the therapeutic regimen is discussed; the available long term data is also presented. The data presented was obtained from a PubMed search as well as a review of the references presented in the 2011 American College of Rheumatology Recommendations for the Treatment of Juvenile Idiopathic Arthritis and the 2013 Update. It is hoped that treatment with etanercept and other biologic therapies will lead to improved outcomes for children with JIA in the future.
23341116 Sjögren's syndrome in older patients: aetiology, diagnosis and management. 2013 Mar Sjögren's syndrome (SS) is a systemic autoimmune disease, characterized by chronic inflammation of exocrine glands that results in development of xerostomia and keratoconjunctivitis sicca. The disease activity of SS is not restricted to exocrine glands, and many other organs and organ systems can be involved. Diagnosis of SS in the elderly population can be challenging because xerostomia, dry eyes, symptoms of fatigue, weight loss and muscle pain are also common features of old age. Delay between clinical onset and diagnosis of SS in the elderly may be due to the shared features of SS and old age. The 2002 revised American-European Consensus Group (AECG) classification criteria for SS are the preferred tool used to confirm diagnosis of SS, but recently alternative criteria have been put forward by the American College of Rheumatology (ACR). The AECG criteria set combines subjective symptoms of dry eyes and dry mouth with objective signs of keratoconjunctivitis sicca, salivary gland dysfunction and histopathological (salivary gland biopsy) and serological (autoantibodies against SSA/Ro and SSB/La antigens) features. Treatment of SS in the elderly does not differ from that in younger patients. The aims of the treatment of SS are to control glandular and extraglandular manifestations, to prevent damage to organ systems and loss of function, and to decrease morbidity and mortality. Treatment of the elderly can be complicated by co-morbidities, an increased rate of adverse events related to therapeutic agents, and polypharmacy. Therefore, careful follow-up of the treatment is required.
25211404 A case of multicentric reticulohistiocytosis. 2017 Jan Multicentric reticulohistiocytosis (MRH) is a rare non-Langerhans histiocytosis of unknown etiology with a predilection for joint and skin. The characteristic clinical features are papulonodular skin eruptions and inflammatory polyarthritis, sometimes progressive to arthritis mutilans, a severe destructive arthropathy. Although these manifestations can present at the same time, it is more common that one feature precedes the others. Notably, these features are similar to those found in some rheumatic diseases, such as rheumatoid arthritis or dermatomyositis, and this can lead to a misdiagnosis, especially during periods where only one feature is present. Herein, we report a female patient with polyarthralgia and subsequent skin eruptions, who was eventually diagnosed with MRH. Her symptoms seemed to resemble those of some rheumatic diseases, but several features such as affected joints and the characteristic shape of the skin lesions did not correspond to that. The histological result of infiltration of histiocytes and multinucleated giant cells in the skin ultimately facilitated the correct diagnosis. In this paper, we review MRH briefly and highlight several differential points which enable us to increase the likelihood of correctly diagnosing MRH.
24660085 Ramsay hunt syndrome in a patient with rheumatoid arthritis after treatment with inflixima 2014 A 39-year-old female patient with rheumatoid arthritis developed Ramsay Hunt syndrome after infliximab treatment. This condition is caused by the reactivation of varicella zoster virus infection in the geniculate ganglion of facial nerve in the host's immunosuppression. She was treated immediately with valaciclovir and hydrocortisone, and the complete recovery was achieved at 6 months after the onset. This is the first report of Ramsay Hunt syndrome as an adverse effect of infliximab in rheumatoid arthritis.
25568848 Recurrent pneumothorax after etanercept therapy in a rheumatoid arthritis patient: a case 2014 Dec The use of anti-tumor necrosis factor (anti-TNF) agents for rheumatoid arthritis (RA) patients who are refractory to disease-modifying anti-rheumatic drugs is gradually increasing. Etanercept is the first anti-TNF agent to be approved for RA treatment and is also the most widely used. However, aggravation of interstitial lung disease after etanercept treatment in RA patients has been reported recently. We report the first case of recurrent spontaneous pneumothorax with progression of interstitial lung disease after initiating etanercept therapy. The withdrawal of etanercept and a change to adalimumab, a different class of TNF inhibitor, achieved clinical stabilization.
23515130 The kinase inhibitor tofacitinib in patients with rheumatoid arthritis: latest findings an 2013 Feb Macrophages, T and B cells, and neutrophils concentrate mainly into the synovial tissue of rheumatoid arthritis (RA) patients and produce several inflammatory mediators including cytokines. More recently, small molecule inhibitors of signalling mediators which have intracellular targets (mainly in T and B cells) such as the Janus kinase (JAK) family of tyrosine kinases have been introduced in RA treatment. The JAK family consist of four types: JAK1, JAK2, JAK3 and TyK2. In particular, JAK3 is the only JAK family member that associates with just one cytokine receptor, the common gamma chain, which is exclusively used by the receptors for IL-2, IL-4, IL-7, IL-9, IL-15 and IL-21 critically involved in T and natural killer (NK)-cell development, and B-cell function and proliferation. Tofacitinib is one of the first JAK inhibitors tested and mainly interacts with JAK1 and JAK3. Four phase II (one A and three B dose-ranging) trials in RA patients, lasting from 6 to 24 weeks, achieved significant improvements of American College of Rheumatology 20% improvement criteria (ACR20) and Disease Activity Score in 28 joints using the C-reactive protein level (DAS28-CRP) or erythrocyte sedimentation rate (DAS-ESR; in one study that analysed this), as early as week 2 and sustained at week 24 in two studies. Doses ranged from 1, 3, 5, 10, 15, 20 up to 30 mg and were administered orally twice a day. ACR20 response rates for dosages ≥3 mg were found to be significantly (p ≤ 0.05) greater than those for placebo in all phase II studies. In general, the major adverse effects included liver test elevation, neutropenia, lipid and creatinine elevation and increased incidence of infections. More recently, RA patients randomly assigned to 5 or 10 mg of tofacitinib twice daily, in both 6- and 12-month phase III trials, achieved a significantly higher ACR20 than those receiving placebo. Adverse events occurred more frequently with tofacitinib than with placebo, and included pulmonary tuberculosis and other serious infections. The balance of efficacy and safety of tofacitinib compared with standard of care therapy is bringing this first orally available biological disease-modifying antirheumatic drug (DMARD) a step closer for RA patients.
25425755 Novel Curcumin Diclofenac Conjugate Enhanced Curcumin Bioavailability and Efficacy in Stre 2014 Sep Curcumin-diclofenac conjugate as been synthesized by esterification of phenolic group of curcumin with the acid moiety of diclofenac, and characterized by mass spectrometry, NMR, FTIR, DSC, thermogravimetric analysis and X-ray diffraction analysis. The relative solubility of curcumin-diclofenac conjugate, curcumin and diclofenac; stability of curcumin-diclofenac conjugate in intestinal extract; permeability study of curcumin-diclofenac conjugate using the everted rat intestinal sac method; stability of curcumin-diclofenac conjugate in gastrointestinal fluids and in vitro efficacy have been evaluated. In vivo bioavailability of curcumin-diclofenac conjugate and curcumin in Sprague-Dawley rats, and antiarthritic activity of curcumin-diclofenac conjugate, curcumin and diclofenac in modified streptococcal cell wall-induced arthritis model in Balb/c mice to mimic rheumatoid arthritis in humans have also been studied. In all of the above studies, curcumin-diclofenac conjugate exhibited enhanced stability as compared to curcumin; its activity was twice that of diclofenac in inhibiting thermal protein denaturation taken as a measure of in vitro antiinflammatory activity; it enhanced the bioavailability of curcumin by more than five folds, and significantly (P<0.01) alleviated the symptoms of arthritis in streptococcal cell wall-induced arthritis model as compared to both diclofenac and curcumin.
25130453 Is the frequent sonographic anechoic area distally in metacarpophalangeal joints a sign of 2014 Oct In clinical practice, ultrasonography (US) often reveals, in the dorsal scan, a small anechoic area distally in both inflamed and clinically non-inflamed metacarpophalangeal joints. This "distal anechogenicity in the metacarpophalangeal joint" (DAEM) might thus be scored false positively as arthritis. We aimed to investigate whether the DAEM is a sign of arthritis. We evaluated the prevalence of DAEMs in 24 non-arthritic subjects. We then compared the dimensions of the DAEM in 10 non-arthritic subjects with a DAEM and 7 consecutive rheumatoid arthritis (RA) outpatients, using 2-D and 3-D ultrasound. Furthermore, we dissected two fresh-frozen postmortem hand specimens after US. A DAEM was observed in the metacarpophalangeal 2 (MCP2) joints of 54% of the 24 non-selected non-arthritic individuals; in none of those did the joint exhibit a power Doppler signal. A DAEM was observed in 86% of the 7 RA patients. Dimensions of DAEMs did not statistically significantly differ between these groups. At 3-D imaging and dissection, the DAEM was found to be an extension of the metacarpophalangeal joint capsule. In conclusion, DAEMs occur frequently and are not a sign of arthritis, but are distal joint recesses. This should be taken into account when using current sensitive ultrasonographic scoring systems grading arthritis.
24028811 [Lyme arthritis in children: a diagnostic trap]. 2013 Oct Lyme disease incidence is diverse in France. It is rare in many regions but very frequent in Central and Eastern France. Arthritis is a late manifestation of Lyme disease. In children, the clinical and biological picture often resembles that of septic arthritis and juvenile rheumatoid arthritis, which are more frequent. This explains why diagnosis may be delayed, especially when patient lives in a region of low incidence. We report the case of an 8-year old girl with knee arthritis treated as septic arthritis in a region where Lyme disease is rare. Six days later, clinical and biological worsening suggested that the diagnosis had to be reconsidered. Lyme arthritis was confirmed by serology. Treatment was adapted and the progression was positive. This case reminds us that, in children, Lyme arthritis may look alike septic arthritis or juvenile rheumatoid arthritis and must be considered as a possible diagnosis, even in low-incidence areas.
24672560 Serum levels of IL-17, IL-4, and INFγ in Serbian patients with early rheumatoid arthritis 2014 Jan BACKGROUND: Rheumatoid arthritis (RA) is a chronic, systemic, inflammatory disease with autoimmune etiology, characterized by synovial inflammation and destruction of joint cartilage and bone. There are controversial data about the profile of interleukin-17 (IL-17A), interleukin-4 (IL-4), and interferon-gamma (INFγ), indicating in some studies the key role of IL-17, while in others the Th1 cytokines. MATERIALS AND METHODS: Serum samples of 31 early RA patients were evaluated for erythrocytes sedimentation rate (ESR), rheumatoid factor (RF), C-reactive protein (CRP), anti-cyclic citrullinated peptide antibodies (anti-CCP), and for the tested cytokines (IL-17A, IL-4, and INFγ). Disease activity score (DAS28) calculation was done for all patients. Control serum samples were obtained from 29 healthy volunteers. RESULTS: The levels of tested cytokines were significantly higher (IL-17A, p < 0.001; INFγ, p < 0.001; IL-4, p < 0.01) in patients with early RA, compared to the healthy controls. In early RA patients, a strong correlation of serum IL-17A was found with DAS28, ESR, and CRP. Also, significant negative correlation was found between serum INFγ levels and the DAS28 score, indicating that INFγ may play a key role in maintaining immune homeostasis in patients with RA. CONCLUSION: The mean serum IL-17A levels in patients with early RA, corresponded with the disease activity and severity. This might highlight the usefulness of the serum IL-17A level in defining the activity and predictive patterns, for aggressive disease therapy, and it might express specific therapeutically targets.
26229794 Clinical and functional evaluation of forefoot reconstruction in patients with rheumatoid 2014 Mar OBJECTIVE: to evaluate the long-term results from reconstruction of the forefoot in patients with rheumatoid arthritis who underwent arthrodesis of the metatarsophalangeal joint of the hallux, resection arthroplasty of the heads of the lateral metatarsals and correction of the deformities of the smaller toes through arthrodesis of the proximal interphalangeal joint or closed manipulation. METHODS: seventeen patients (27 feet) who underwent forefoot reconstruction surgery by means of arthrodesis of the first metatarsophalangeal joint, resection of the heads of the lateral metatarsals and correction of the deformities of the smaller toes, were studied retrospectively. The mean follow-up was 68 months (12-148 months); the mean age was 52 years (range: 20-75 months); and four patients were male and 13 were female. RESULTS: the results were classified as excellent in 17 feet, good in two, fair in four and poor in two. The mean score on the AOFAS scale was 70 points; 21 feet (78%) were found to be asymptomatic; and six feet (22%) presented some type of symptom. Three feet presented pseudarthrosis, and one of these successfully underwent revision of the arthrodesis. There was no significant difference in scoring on the AOFAS scale or in the consolidation rate, between using a plate and screws and using Kirschner wires for fixation of the arthrodesis. CONCLUSION: arthrodesis of the first metatarsophalangeal joint with resection arthroplasty on the heads of the lateral metatarsals and correction of the deformities of the smaller toes, which was used in forefoot reconstruction in rheumatoid patients, showed good long-term results with a high satisfaction rate among the patients and clinical-functional improvement.
23986797 Peripheral corneal ulceration associated with rheumatoid arthritis. 2013 PATIENT: Female, 60 FINAL DIAGNOSIS: Corneal ulceration Symptoms: Blurred vision Medication: Abatacept Clinical Procedure: - Specialty: Ophthalmology. OBJECTIVE: Management of emergency care. BACKGROUND: To report a case of a patient with rheumatoid arthritis (RA) and associated peripheral corneal ulceration. CASE REPORT: A 60-year-old woman with RA diagnosed 15 years ago, under immunosuppressive therapy (IV abatacept 250 mg/month), demonstrated blurring of vision in her RE (right eye). Visual acuity was 6/10 in the RE and 10/10 in the LE. Slit lamp examination revealed a paracentral superior corneal melt in the RE. Anterior chamber reaction was 2+. Laboratory investigations revealed positive anti-Ro and anti-La, anti-Extractable Nuclear Antigens (anti-ENA, ELISA), while anti-Sm, anti-Rnp, anti-Jo1 and anti-Scl70 were found negative. IgG and IgA serum immunoglobulins were found elevated, but IgE and IgM were within normal levels. Further evaluation for the underlying disease revealed highly elevated rheumatoid factor and C-reactive protein. The patient, who had been receiving anti-TNF during the last 6 months, underwent treatment with topical tobramycin and lubricants and oral prednisone 60 mg/day with tapering doses, to which methotrexate p.os. 15 mg/week was added. The condition improved within a few days after the initiation of prednisone treatment. Re-epithelization occurred 1 week after the onset of the immunosuppressive treatment. Only punctate fluorescein dye uptake was detected in the margins of the lesion. CONCLUSIONS: The effective control of the underlying disease and early diagnosis of the dry eye syndrome in RA patients may prevent serious corneal complications such as corneal ulceration. The initiation of treatment with steroids and immunosuppresants was found to halt the progression of keratolysis, and assisted re-epithelization.
24630585 [Paradoxical cutaneous reactions associated with tocilizumab therapy]. 2014 Sep INTRODUCTION: Tocilizumab (TCZ) is a humanized antihuman interleukin (IL)-6 receptor antibody recommended for the treatment of moderate to severe active rheumatoid arthritis, adult-onset Still disease, Castleman disease and more recently, systemic juvenile idiopathic arthritis. Like anti-TNFα, rituximab and less frequently abatacept, TCZ can induce paradoxical cutaneous eruption like psoriasis with predominantly palmoplantar presentation. CASE REPORT: We report a 47-year-old woman with psoriastic arthritis who developed under anti-TNFα therapy and later under tocilizumab a paradoxical palmoplantar eruption. CONCLUSION: The specific underlying mechanisms of this side effect are unclear but relapse of these lesions seems to be observed with certain biological agents.
24940448 Effect of γ-tocotrienol in counteracting oxidative stress and joint damage in collagen-in 2014 May Tocotrienols exhibit a significant anti-inflammatory and antioxidant effect in numerous human diseases. However, the anti-inflammatory and antioxidant effects of tocotrienols in arthritic conditions are not well documented. Therefore, the effect of γ-tocotrienol supplementation against oxidative stress and joint pathology in collagen-induced arthritis in rats was investigated in the present study. Adult female Dark Agouti rats were randomly divided into groups: Control, γ-tocotrienol alone, arthritis alone and arthritis with γ-tocotrienol. Arthritis was induced using 4 mg/kg body weight collagen in complete Freund's adjuvant. The rats were treated orally with 5 mg/kg body weight of γ-tocotrienol between day 21 and day 45. After 45 days, serum C-reactive protein (CRP), tumor necrosis factor (TNF)-α, superoxide dismutase (SOD) and total glutathione (GSH) assays were conducted. γ-tocotrienol significantly reduced the arthritis-induced changes in body weight, CRP, TNF-α, SOD and the total GSH levels. There was a significant reduction in the arthritis-induced histopathological changes in the γ-tocotrienol treatment group. The data indicated that administration of γ-tocotrienol resulted in a significant antioxidant and anti-inflammatory effect on collagen-induced arthritis; therefore, γ-tocotrienol may have therapeutic potential as a long-term anti-arthritic agent in rheumatoid arthritis therapy.
24439153 Dual diagnosis: rheumatoid arthritis and multiple sclerosis. 2014 Jan Juvenile rheumatoid arthritis (JRA) is the most common rheumatologic disease in children. Moreover, multiple sclerosis (MS) is the most frequent demyelinating disease and has been associated with various chronic inflammatory diseases. However, its association with JRA has not been frequently described. Autoimmunity in both JRA and MS has been documented in the scientific literature, although there has been no definitive finding that patients with JRA are prone to the development of MS. An increasing frequency of MS resulting from an increased use of antitumor necrosis factor agents in the treatment of rheumatoid arthritis and other chronic inflammatory diseases has been reported recently. In this study, we report on the development of MS in a patient with JRA who did not have a history of antitumor necrosis factor use.
25035831 Perioperative management of the patient with rheumatoid arthritis. 2014 Jul 18 A multidisciplinary approach is required to care for patients with rheumatoid arthritis (RA) in the perioperative period. In preparation for surgery, patients must have a cardiovascular risk assessment performed due to the high risk of heart disease in patients with RA. Treatment of RA is with immunomodulatory medications, which present unique challenges for the perioperative period. Currently, there is no consensus on how to manage disease modifying antirheumatic drug (DMARD) therapy in the perioperative setting. Much of the data to guide therapy is based on retrospective cohort data. Choices regarding DMARDs require an individualized approach with collaboration between surgeons and rheumatologists. Consensus regarding biologic therapy is to hold the therapy in the perioperative period with the length of time dictated by the half-life of the medication. Special attention is required at the time of surgery for potential need for stress dose steroids. Further, there must be close communication with anesthesiologists in terms of airway management particularly in light of the risk for cervical spine disease. There are no consensus guidelines regarding the requirement for cervical spine radiographs prior to surgery. However, history and exam alone cannot be relied upon to identify cervical spine disease. Patients with RA who undergo joint replacement arthroplasty are at higher risk for infection and dislocation compared to patients with osteoarthritis, necessitating particular vigilance in postoperative follow up. This review summarizes available evidence regarding perioperative management of patients with RA.
24860653 Advances in the treatment of rheumatoid arthritis. 2014 The intense pursuit of novel therapies in rheumatoid arthritis has provided physicians with an assorted set of biologic drugs to treat patients with moderate to severe disease activity. Nine different biologic therapies are currently available: seven inhibitors of pro-inflammatory cytokines (five targeting tumor necrosis factor [TNF], one interleukin [IL]-1 and one IL-6), as well as a T- and a B-lymphocyte targeting agent. All these drugs have roughly similar efficacy profiles and are approved as first- or second-line therapy in patients who failed to respond to conventional disease-modifying anti-rheumatic drugs (DMARDs) and in most cases for first line use in rheumatoid arthritis as well. Despite the irrefutable clinical and radiological benefits of biologic therapies, there are still low rates of patients achieving stable remission. Therefore, the quest for new and more effective biologic therapies continues and every year new drugs are tested. Simultaneously, optimal use of established agents is being studied in different ways. Recently, the approval of the first small molecule targeting intracellular pathways has opened a new chapter in the treatment of rheumatoid arthritis. Other emerging treatment strategies include the activation of regulatory T cells as well as new cytokine-targeting therapies.
24649081 Association of ultraviolet radiation resistance-associated gene polymorphisms with rheumat 2014 Jan The ultraviolet radiation resistance-associated gene (UVRAG) protein binds to the Beclin 1/PI3-kinase III complex and promotes autophagy. Autophagy may be upregulated by endoplasmic reticulum (ER) stress. Persistent and excessive ER stress may alter synovial fibroblast apoptosis and this alteration may affect the pathogenesis of rheumatoid arthritis (RA). In this study, we investigated whether UVRAG genetic polymorphisms are associated with RA. To determine the association between UVRAG polymorphisms and RA, we genotyped five UVRAG single-nucleotide polymorphisms (SNPs; rs7111334, intron C/T; rs7933235, intron A/G; rs1380075, intron T/A; rs1458836, near the 5' gene terminal G/A; and rs636420, exon 15 C/T) using a direct sequencing method in 243 RA patients and 417 control subjects. Among these, one SNP (rs7111334) exhibited significant genotypic/allelic differences between RA patients and the control group. Therefore, this study suggested a possible association between UVRAG polymorphisms and RA susceptibility.
24382953 NSAID-Induced Enteropathy in Rheumatoid Arthritis Patients with Chronic Occult Gastrointes 2013 Background. The purpose of study was to evaluate the diagnostic yield of capsule endoscopy for NSAID-induced enteropathy and clinical, laboratory, and endoscopic characteristics of disease in patients with rheumatoid arthritis. Methods. 37 rheumatoid arthritis patients (30 women; mean age 55) treated with NSAIDs (>1 month), presented with anaemia and/or positive faecal occult blood testing, entered the study and underwent capsule endoscopy (EndoCapsule; Olympus), laboratory tests, and filled in questionnaires. Results. The prevalence of NSAID-induced enteropathy diagnosed by capsule endoscopy was 68% (25/37), classified as mild (red spots or erosions) in 18 (49%), moderate (10-20 erosions) in 4 (11%), and severe enteropathy (>20 erosions or ulcers) in 3 (8%) patients. We did not find statistically significant relationship between the enteropathy and gender, age, haemoglobin, leukocytes, albumin and CRP, or dyspepsia. The difference between subgroups of NSAIDs according to the COX specificity was not statistically significant. Conclusions. Capsule endoscopy is a highly accurate noninvasive method for evaluation of NSAID-induced enteropathy. It was revealed in a substantial section of the patients with rheumatoid arthritis and occult gastrointestinal bleeding, mostly classified as mild damage. No simple clinical or laboratory markers of the presence or severity of NSAID-induced enteropathy were recognised. This trial is registered with DRKS00004940.