• Humans
• Crohn Disease/diagnosis
• Crohn Disease/therapy
• Gastroenterology/standards
• Germany

• Enfermedades inflamatorias intestinales
• Inflammatory bowel diseases
• Monitoring
• Monitorización
• Personalizada
• Personalized
• Tratamiento por objetivos
• Treat to target

• Humans
• Precision Medicine
• Inflammatory Bowel Diseases/drug therapy
• Inflammatory Bowel Diseases/therapy
• Crohn Disease/drug therapy
• Crohn Disease/therapy
• Colitis, Ulcerative/drug therapy
• Colitis, Ulcerative/therapy
• Quality of Life

• UST
• VDZ
• intestinal activity
• joint symptoms
• spondyloarthritis

• Biologic therapies
• Crohn’s disease
• Early effective therapy
• IBD
• Pediatric
• Precision medicine
• Ulcerative colitis

• Child
• Humans
• Colitis, Ulcerative/drug therapy
• Crohn Disease/drug therapy
• Inflammatory Bowel Diseases/drug therapy
• Precision Medicine
• Prognosis
• Biological Therapy

• K23 DK125760 NIDDK NIH HHS

• Inflammatory bowel disease
• artificial intelligence
• drug pharmacokinetics
• patient phenotype
• personalized medicine

• Spondyloarthropathy
• biologicals
• inflammatory bowel disease

• Adalimumab
• Biological therapy
• Infliximab
• Monoclonal antibodies
• Ustekinumab
• Vedolizumab

• Crohn’s disease
• Inflammatory bowel disease
• anti-TNF therapy
• biologic therapy
• extra-intestinal manifestations
• tofacitinib
• ulcerative colitis
• ustekinumab
• vedolizumab

• Biological Products/adverse effects
• Colitis/complications
• Humans
• Inflammatory Bowel Diseases/complications
• Inflammatory Bowel Diseases/diagnosis
• Inflammatory Bowel Diseases/drug therapy

To describe and identify factors associated with articular manifestations occurring in patients treated with anti-tumour necrosis factor (TNF) for inflammatory bowel diseases (IBDs).

Retrospective monocentric study, including all patients who received an anti-TNF for an IBD in our hospital. All incident articular manifestations occurring during treatment were analysed. Characteristics of patients with paradoxical articular manifestations were compared with that of patients without inflammatory articular manifestations.

Between February 2013 and May 2017, we identified 442 patients (36.2±15 years, 50.5% men) who had ever received an anti-TNF for an IBD: Crohn’s disease (n=277), ulcerative colitis (n=154) and undetermined colitis (n=11). 115 (26%) patients developed new articular manifestations after a mean of 20 (±22) months of treatment. Among them, 59 (13.3%) had inflammatory manifestations: paradoxical in 39%, concomitant of an IBD flare in 27%, linked to an immunisation against anti-TNF in 27% and 7% to another diagnosis. Among paradoxical articular manifestations, 19 (83%) were new articular symptoms, including 8 (35%) de novo spondyloarthritis. There were no predictive factors of paradoxical articular manifestation. Paradoxical manifestations spontaneously resolved in 16 (70%) patients despite continuation of anti-TNF.

Inflammatory articular manifestations occurred in about 13% of patients treated with anti-TNF for IBD. More than a quarter were linked to an immunisation against anti-TNF, which has to be searched in this situation. About 40% were paradoxical. In most of cases, they were transitory and did not require anti-TNFs discontinuation.

• ankylosing
• antirheumatic agents
• spondylitis
• tumor necrosis factor inhibitors

• arthritis
• crohn's disease
• inflammatory bowel disease
• infliximab
• ulcerative colitis

• arthritis
• autoimmune diseases
• spondyloarthritis
• tumour necrosis factor inhibitors

• Gastrointestinal Microbiome
• Humans
• Inflammatory Bowel Diseases/drug therapy
• RNA, Ribosomal, 16S/genetics
• Spondylarthritis/drug therapy
• Tumor Necrosis Factor Inhibitors
• Tumor Necrosis Factor-alpha

• Crohn’s disease
• infliximab
• prediction
• primary non-response
• serum biomarkers

• anti-tnf therapy
• arthralgia
• crohn's disease
• infliximab

• IBD clinical
• TNF
• arthritis

Background and Aims: The Inflammatory Bowel Diseases (IBDs), Crohn’s Disease (CD) and Ulcerative Colitis (UC), are gastrointestinal autoimmune disorders with many Extraintestinal Manifestations (EIMs). Previously reported incidences of EIMs in IBD patients have ranged from 10% to 50%. The large variation in occurrence of EIMs has been linked to genetic predisposition. Correlations between individual EIMs are unclear. Therefore, we aim to estimate the incidence of EIMs in a Middle Eastern cohort of patients with IBD and examine possible relationships with EIMs.

Patients and Methods: We conducted a retrospective study involving all patients included in the King Abdulaziz University IBD information system registry between 2013 and 2018. Data on demographics, disease characteristics, and EIMs were extracted and analyzed using descriptive statistics: the standard Student’s t-test and chi-squared test. Logistic regression analysis was used to examine associations using STATA software version 11.2 (StataCorp, TX, USA).

Results: We reviewed the electronic medical files of 284 patients with confirmed IBD, of which 158 (55.6%) were females, the mean age was 27.8 (±15) years; 146 (51.4%) patients had CD and 138 (48.6%) UC. The overall incidence risk of EIMs was 138 (52.3%) over a mean duration of follow up of 7.3 (±3.9) years. The most common EIM was arthritis (33%), followed by aphthous ulcers (16%). Pyoderma gangrenosum occurred in 8% of patients and appeared to be specific for CD patients (p = 0.002), whereas Primary Sclerosing Cholangitis (PSC) was more specific for UC (p = 0.001). Certain EIMs appeared to occur together such as arthritis with PSC (p = 0.001). Regression analysis identified disease type (in favor of UC; odds ratio = 0.50, p = 0.03) and age at the time of diagnosis (odds ratio = 1.04, p = 0.001) as the only significant predictors of EIMs.

Conclusion: Our results demonstrate that more than half of IBD patients have at least one EIM. Contrary to what has often been reported, we found that EIMs occur more commonly in UC than CD. A multidisciplinary assessment is recommended as part of IBD management to improve overall health outcomes.

• Inflammatory bowel disease
• extraintestinal
• incidence
• manifestations
• predictors

• Crohn’s disease
• Extraintestinal manifestations
• axial spondyloarthritis
• diagnosis and follow-up
• primary sclerosing cholangitis
• ulcerative colitis

• Extraintestinal manifestation
• Occult pulmonary disease
• Pulmonary involvement
• Restrictive pattern
• Ulcerative colitis

• TNF-inhibition
• colonic mucosa tissue
• inflammatory bowel disease
• paradoxical arthritis
• synovial tissue

Extraintestinal manifestations (EIMs) in patients with Crohn’s disease (CD) are common and associated with additional morbidity. This study aimed to evaluate the effect of adalimumab therapy on EIM resolution and identify potential predictors of EIM resolution in adult and pediatric patients with moderate to severe CD.

EIM data were pooled from 11 induction, maintenance, and open-label extension studies of adalimumab. Resolution of EIMs was evaluated at approximately 6 months and 1 year. Median time to initial EIM resolution and first EIM recurrence (reflecting durable resolution) of any EIM and specific categories of EIMs (arthritis/arthralgia, ocular, cutaneous) were calculated. A Cox model was used to determine predictors of initial and durable EIM resolution.

At baseline, 54% (1137/2094) of patients receiving adalimumab and 51% (297/586) receiving placebo had EIMs. EIM resolution occurred in a significantly greater proportion of adalimumab versus placebo patients at 6 months (54% vs 31%; P < .001) and 1 year (60% vs 42%; P = .008). Median time to initial resolution of any EIM, arthritis/arthralgia, and cutaneous EIMs was significantly shorter in patients receiving adalimumab versus placebo. Durable resolution of any EIM and arthritis/arthralgia was significantly longer for patients receiving adalimumab versus placebo. Clinically meaningful predictors of EIM resolution included adalimumab treatment, male sex, and moderate (versus severe) disease activity at baseline.

Adalimumab is effective for achieving initial and durable resolution of any EIM and, in particular, arthritis/arthralgia in patients with moderate to severe CD. Predictors of EIM resolution included adalimumab treatment and moderate disease severity.

AbbVie.

The online version of this article (10.1007/s12325-018-0678-0) contains supplementary material, which is available to authorized users.

• Adalimumab
• Arthralgia
• Arthritis
• CDAI
• Crohn’s disease
• Extraintestinal manifestation
• Gastroenterology
• Inflammatory bowel disease

• Arthritis
• Inflammation
• Spondyloarthritis
• Treatment

• Antibodies, Monoclonal, Humanized
• Humans
• Inflammatory Bowel Diseases
• Sacroiliitis
• Spondylarthritis

• Colitis, Ulcerative/complications
• Colitis, Ulcerative/diagnosis
• Colitis, Ulcerative/pathology
• Colitis, Ulcerative/therapy
• Colorectal Neoplasms/diagnosis
• Colorectal Neoplasms/etiology
• Colorectal Neoplasms/prevention & control
• Early Detection of Cancer
• Evidence-Based Medicine
• Female
• Humans
• Opportunistic Infections/etiology
• Population Surveillance
• Pouchitis/diagnosis
• Pouchitis/therapy
• Pregnancy
• Pregnancy Complications/diagnosis
• Pregnancy Complications/therapy
• Proctocolectomy, Restorative/adverse effects
• Severity of Illness Index
• Terminology as Topic

• Extraintestinal Manifestations
• Inflammatory Bowel Disease
• Systematic Review

• extraintestinal manifestations
• inflammatory bowel disease
• arthritis
• uveitis

• Biliary Tract Diseases/etiology
• Eye Diseases/etiology
• Humans
• Inflammatory Bowel Diseases/complications
• Liver Diseases/etiology
• Musculoskeletal Diseases/etiology
• Prognosis
• Skin Diseases/etiology

• TNF-α inhibitors
• enteropathic arthritis
• inflammatory bowel disease

• Anemia
• Colitis ulcerosa
• Manifestaciones extraintestinales
• Pouchitis
• Psicosomática
• Vigilancia del cáncer colorrectal

• Acute Disease
• Aftercare/methods
• Chronic Disease
• Colitis, Ulcerative/complications
• Colitis, Ulcerative/psychology
• Colitis, Ulcerative/surgery
• Colonoscopy
• Colorectal Neoplasms/diagnosis
• Colorectal Neoplasms/etiology
• Colorectal Neoplasms/therapy
• Disease Progression
• Humans
• Postoperative Complications/diagnosis
• Postoperative Complications/therapy
• Pouchitis/diagnosis
• Pouchitis/etiology
• Pouchitis/therapy
• Proctocolectomy, Restorative
• Risk Factors

• Extraintestinal manifestations
• Inflammatory bowel disease
• Infliximab
• Sacroiliitis
• Spondyloarthropathy

• Adolescent
• Age of Onset
• Anti-Inflammatory Agents/therapeutic use
• Child
• Colitis, Ulcerative/complications
• Crohn Disease/complications
• Disease Progression
• Gastrointestinal Agents/therapeutic use
• Humans
• Inflammation Mediators/metabolism
• Inflammatory Bowel Diseases/complications
• Inflammatory Bowel Diseases/diagnosis
• Inflammatory Bowel Diseases/drug therapy
• Inflammatory Bowel Diseases/immunology
• Remission Induction
• Signal Transduction
• Spondylarthropathies/diagnosis
• Spondylarthropathies/drug therapy
• Spondylarthropathies/etiology
• Spondylarthropathies/immunology
• Treatment Outcome

• Cholangitis, Sclerosing/diagnosis
• Cholangitis, Sclerosing/etiology
• Cholangitis, Sclerosing/therapy
• Genetic Predisposition to Disease
• Humans
• Inflammatory Bowel Diseases/complications
• Inflammatory Bowel Diseases/diagnosis
• Inflammatory Bowel Diseases/therapy
• Scleritis/diagnosis
• Scleritis/etiology
• Scleritis/therapy
• Uveitis/diagnosis
• Uveitis/etiology
• Uveitis/therapy

• Anemia/diagnosis
• Anemia/drug therapy
• Anemia/etiology
• Anxiety/complications
• Anxiety/therapy
• Biliary Tract Diseases/diagnosis
• Biliary Tract Diseases/etiology
• Biliary Tract Diseases/therapy
• Bone Diseases, Metabolic/diagnosis
• Bone Diseases, Metabolic/etiology
• Bone Diseases, Metabolic/therapy
• Colitis, Ulcerative/complications
• Colitis, Ulcerative/psychology
• Colorectal Neoplasms/diagnosis
• Depression/complications
• Depression/therapy
• Early Detection of Cancer
• Evidence-Based Medicine
• Eye Diseases/diagnosis
• Eye Diseases/drug therapy
• Humans
• Joint Diseases/diagnosis
• Joint Diseases/drug therapy
• Joint Diseases/etiology
• Liver Diseases/diagnosis
• Liver Diseases/etiology
• Liver Diseases/therapy
• Population Surveillance
• Pouchitis/diagnosis
• Pouchitis/therapy
• Skin Diseases/drug therapy
• Venous Thromboembolism/diagnosis
• Venous Thromboembolism/drug therapy
• Venous Thromboembolism/etiology
• Venous Thromboembolism/prevention & control

Kortikosteroide waren die ersten Therapeutika zur Kontrolle von Abstoßungsreaktionen nach Transplantation. Sie sind seit Langem und immer noch wichtiger Bestandteil vieler immunsuppressiver Therapiekonzepte. Kortikosteroide besitzen zahlreiche antiinflammatorische und immunsuppressive Effekte. Sie beeinflussen über die Bindung spezifischer zytoplasmatischer Rezeptoren die Gentranskriptionsrate für zentrale, immunregulatorische Proteine wie Interleukin 1β (IL-1β), IL-6, Tumor-Nekrose-Faktor α (TNF-α) mit resultierender Suppression der Makrophagenfunktion und konsekutiver T-Zell-Aktivierung. Sie inhibieren auch die IL-2-Synthese, hemmen damit die T-Zell-Proliferation und reduzieren die IL- 2-Rezeptorbindungsfähigkeit. Andererseits stimulieren sie die Synthese des inhibierenden Zytokins „transforming growth factor β“ (TGF-β), was in einem „antiinflammatorisch“ geprägten T-Helfer-Zell-2-artigen Zytokinprofil resultiert. Über die Inhibition der Expression von interferonabhängigen Adhäsionsmolekülen (einschließlich MHC-Klasse-II-Moleküle) bewirken Kortikosteroide darüber hinaus die Alteration von Leukozytenverkehr und -transmigration sowie eine Induktion der Lymphozytenapoptose.

Enteropathic arthritis is one of the recognized extraintestinal manifestations of inflammatory bowel disease and affects up to 25% of patients. The treatment options for refractory disease were rather limited and ineffective until the arrival of biologic therapy in the last few years. The use of etanercept was unique for this disease.

In this case report, a 58-year-old Malay woman with a 17-year history of ulcerative colitis had persistent left knee effusion and synovitis for seven years, despite remission of the primary disease. She had had multiple courses of systemic and intra-articular steroid that caused significant systemic side effects such as impaired fasting glucose, hypertension, cataract, and weight gain. She also had a total left knee replacement for secondary osteoarthritis. But the left knee synovitis and effusion recurred a month after the total knee replacement, and she was subjected to a total synovectomy the following year. In view of failure of remission despite multiple immunosuppressants (100 mg of azathioprine daily, 1 g of sulfasalazine twice a day, 10 mg of prednisolone daily, and 10 mg of methotrexate weekly), 25 mg of subcutaneous etanercept twice weekly was started. After 5 weeks of treatment, complete resolution of left knee effusion and normalization of the inflammatory markers were shown. This continued up to 12 months of follow-up while our patient was on etanercept and 10 mg of methotrexate weekly. No relapse or serious side effects were noted.

This case demonstrates the efficacy of etanercept in recalcitrant enteropathic arthritis with no relapse of the underlying colitis while on treatment. The usage of this tumor necrosis factor inhibitor was unique in this case of rheumatology and gastroenterology.

Crohn’s disease (CD) is a chronic inflammatory disease of the gastrointestinal tract characterized by recurring flares followed by periods of inactive disease and remission. The etiology is unknown, although the common opinion is that the disease arises from a disordered immune response to the gut contents in genetically predisposed individuals. Infliximab (IFX), a chimeric immunoglobulin G1 monoclonal antibody to tumor necrosis factor, has dramatically changed the approach to managing patients with CD and improving their treatment, by achieving treatment goals, such as mucosal healing, and decreasing the need for hospitalizations and surgeries. This review provides an update on existing evidence for the use of IFX in CD, taking into account the safety profile in clinical practice and special situations such as pregnancy. Antitumor necrosis factor therapy has been evaluated as an induction and maintenance therapy in CD in several randomized controlled trials and meta-analyses, showing efficacy in both clinical settings. Early use of biologics may improve patient outcomes in active CD. However, a widespread use of a “top-down” approach in all CD patients cannot be recommended. Clinical factors at diagnosis may predict poor outcome in CD, and should be taken into account when determining the initial therapeutic approach.

• Crohn’s disease
• adult
• infliximab

• inflammatory bowel disease
• ibd
• arthritis
• ulcerative colitis
• crohn’s disease
• extraintestinal manifestations
• dmards
• biologics