Anti-tumour Necrosis Factor Alpha Therapy Research Articles

Local fistula injection of allogeneic human amnion epithelial cells is safe and well tolerated in patients with refractory complex perianal Crohn's disease: a phase I open label study with long-term follow up

Local fistula injection of mesenchymal stromal/stem cells (MSC) is effective for complex perianal Crohn's fistulas but is also expensive and requires specialised facilities for cell revival before administration. Human amnion epithelial cells (hAEC) are non-MSC cells with therapeutic properties. The primary aim of this study was safety of hAEC therapy. Secondary aims included hAEC efficacy, feasibility of the protocol and impact on quality of life. A phase I open label study of ten adults with active complex Crohn's perianal fistulas refractory to conventional treatment, including anti-tumour necrosis factor alpha therapy, was undertaken. A single dose of hAEC was injected into the fistula tract(s) after surgical closure of the internal opening(s). Study outcomes were assessed at week 24 with follow up for at least 52 weeks. Local injection of hAEC was safe, well tolerated and the injection procedure was feasible. Complete response occurred in 4 patients, and a partial response in an additional 4 patients. There was a mean reduction in the Perianal Disease Activity Index of 6.5 points (95% CI-9.0 to-4.0, p=0.0002, paired t-test), modified Van Assche MRI Index of 2.3 points (95% CI-3.9 to-0.6, p=0.012, paired t-test) and a mean improvement of 15.8 points (95% CI 4.9 to 26.8, p=0.010, paired t-test) in quality of life using the Short IBD-Questionnaire in complete responders. Local injection of hAEC therapy for refractory complex perianal fistulising Crohn's disease appears safe, well-tolerated, feasible and demonstrated improvement. Quality of life is improved in those who achieve complete fistula healing. This study was funded by competitive research grant funding from the Gastroenterological Society of Australia Seed Grant2018.

Improved Clinical Outcomes With Early Anti-Tumour Necrosis Factor Alpha Therapy in Children With Newly Diagnosed Crohn's Disease: Real-world Data from the International Prospective PIBD-SETQuality Inception Cohort Study.

Treatment guidelines for paediatric Crohn's disease [CD] suggest early use of anti-tumour necrosis factor alpha [anti-TNFα] in high-risk individuals. The aim is to evaluate the effect of early anti-TNF in a real-world cohort. Children with newly diagnosed CD were prospectively recruited at 28 participating sites of the international observational PIBD-SETQuality study. Outcomes were compared at 3 months, 1 and 2 years between patients receiving early anti-TNF [<90 days after diagnosis] and those not receiving early anti-TNF. Outcomes included sustained steroid-free remission [SSFR] without treatment intensification [specified as SSFR*] and sustained steroid-free mild/inactive disease without treatment intensification [specified as SSFMI*]. Penalised logistic regression model-based standardisation was applied to estimate the relative risks [RR] of early therapy on outcomes. RRs were estimated for high-risk and low-risk patients, based on presence of predictors of poor outcome [POPOs] and disease activity at diagnosis. In total, 331 children (median age 13.9 years [IQR 12.2-15.3]) were enrolled, with 135 [41%] receiving early anti-TNF. At 1 year, patients on early anti-TNF had higher rates of SSFR* [30% vs 14%, p <0.001] and SSFMI* [69% vs 33%, p <0.001], with RRs of 2.95 [95% CI 1.63-5.36] and 4.67 [95% CI 2.46-8.87], respectively. At 1 year, the RRs for SSFMI* were higher, and statistically significant in high-risk patients, i.e. those with moderate/severe disease compared with mild/inactive disease at diagnosis (5.50 [95% CI 2.51-12.05] vs 2.91 [95% CI 0.92-9.11]), and those with any POPO compared with no POPO (5.05 [95% CI 2.45-10.43] vs 3.41 [95% CI 0.54-21.7]). In this cohort of children with newly-diagnosed CD, early anti-TNF demonstrated superior effectiveness in high-risk patients.

Haemophagocytic lymphohistiocytosis due to leishmaniasis following anti-tumour necrosis factor-alpha therapy.

Haemophagocytic lymphohistiocytosis due to leishmaniasis following anti-tumour necrosis factor-alpha therapy.

Antitumour necrosis factor alpha treatment in Crohn’s disease: long-term efficacy, side effects and need for surgery

Objectives To examine the long-term efficacy and side effects of antitumour necrosis factor alpha (anti-TNF) therapy in patients with Crohn’s disease (CD), the need for surgery and the clinical outcome after discontinuing anti-TNF therapy. Material and methods Data were collected from the inflammatory bowel disease (IBD)-TNF register at Østfold Hospital Trust. Clinical and sociodemographic data were recorded for patients initiating anti-TNF therapy from January 2000 until December 2011. Follow-up was conducted until December 2017. Results Complete remission (CR) was achieved in 40/154 (26%) patients at the last follow-up (median follow-up time 10 years). A total of 40 (26%) patients had to discontinue treatment due to serious side effects, and malignancy was recorded in 10 (6.5%) patients. Surgical resection was performed in 55 (36%) patients during follow-up. Patients with Montreal phenotype B2 before anti-TNF therapy were estimated to have a 2.54-fold greater risk of surgery than patients with phenotype B1 (p = .001). Of those with phenotype B1 before anti-TNF therapy, 19 (24%) of them developed stenosis in need of surgical resection (‘phenotype migration’). In patients followed up after discontinuing anti-TNF therapy (n = 89, median observational time six years), CR was achieved in most patients. Conclusions Long-term complete remission was achieved in only one in four patients receiving anti-TNF therapy, and one in four patients had to discontinue therapy due to side effects. Despite anti-TNF therapy, one in four patients with a baseline luminal disease phenotype needed subsequent surgical resection.

Polygenetic risk scores do not add predictive power to clinical models for response to anti-TNFα therapy in inflammatory bowel disease.

Anti-tumour necrosis factor alpha (TNFα) therapy is widely used in the management of Crohn's disease (CD) and ulcerative colitis (UC). However, up to a third of patients do not respond to induction therapy and another third of patients lose response over time. To aid patient stratification, polygenetic risk scores have been identified as predictors of response to anti-TNFα therapy. We aimed to replicate the association between polygenetic risk scores and response to anti-TNFα therapy in an independent cohort of patients, to establish its clinical validity. Primary non-response, primary response, durable response and loss of response to anti-TNFα therapy was retrospectively assessed for each patient using stringent definitions. Genome wide genotyping was performed and previously described polygenetic risk scores for primary non-response and durable response were calculated. We compared polygenetic risk scores between patients with primary response and primary non-response, and between patients with durable response and loss of response, using separate analyses for CD and UC. Out of 334 patients with CD, 15 (4%) patients met criteria for primary non-response, 221 (66%) for primary response, 115 (34%) for durable response and 35 (10%) for loss of response. Out of 112 patients with UC, 12 (11%) met criteria for primary non-response, 68 (61%) for primary response, 19 (17%) for durable response and 20 (18%) for loss of response. No significant differences in polygenetic risk scores were found between primary non-responders and primary responders, and between durable responders and loss of responders. We could not replicate the previously reported association between polygenetic risk scores and response to anti-TNFα therapy in an independent cohort of patients with CD or UC. Currently, there is insufficient evidence to use polygenetic risk scores to predict response to anti-TNFα therapy in patients with IBD.

Withdrawal of Combination Immunotherapy in Paediatric Inflammatory Bowel Disease-An International Survey of Practice.

To assess current practices around the use of combination immunosuppression in paediatric inflammatory bowel disease (PIBD) with a focus on the subsequent withdrawal process. A web-based, 43-question survey. Surveys were completed by 70 paediatric gastroenterologists (PGs) from 27 nations across Europe, North America, Oceania and Asia from 62 centres covering approximately 15,000 PIBD patients (median of 200 patients [interquartile range (IQR) 130-300] per centre). Routine use of co-immunosuppression was significantly higher with infliximab (IFX) versus adalimumab (ADL) ([61/70, 87.1%] compared with [23/70, 32.9%]; P < 0.01). Thiopurines (azathioprine [AZA] or 6-mercaptopurine) were the preferred option overall for co-immunosuppression. They were favoured with either IFX or ADL (76% and 77%, respectively) and in both ulcerative colitis (UC) and Crohn disease (CD) (84% and 69%) compared with methotrexate (MTX).Immunomodulators were the preferred choice as the initial drug to be withdrawn from the combination therapy rather than anti-tumour necrosis factor-alpha (anti-TNFα) therapy (59/67, 88% [P < 0.01]). The most common withdrawal time was after 6-12 months, with this decision usually based on clinical assessment rather than a scheduled withdrawal time (51/67, 76% vs 16/67, 24%). Indicators of mucosal healing and therapeutic drug monitoring results tended to be the most important "clinical factors" in the withdrawal decision (P = 0.05). Most PG's favour initial withdrawal of immunomodulator (usually thiopurines) rather than biologic therapy in the step-down process, usually after 6-12 months based on sustained clinical remission. This survey precedes an in-depth, multicentre study of clinical outcomes of withdrawal of co-immunosuppression in PIBD.

Radiofrequency thermocoagulation for high transphincteric fistulae, Merlini l'Héritier et al.

Obliteration of the internal opening has long been held as the key resolution of high transsphincteric fistulae. This month's Editor's Choice by Merlini l'Héritier et al. evaluated ablation of the tract by applying radiofrequency thermocoagulation 1. They used a control group, selected from a prospective database consisting of patients who underwent occlusion of the fistula tract by a rectal advancement flap, paired-matched for sex, age and the presence of Crohn's disease. The healing rate was only 26% at 5 months after radiofrequency thermocoagulation, vs 68% after flap repair, and dropped further to 10% after 21 months. These findings suggest that obliteration of the fistula tract is not enough to accomplish healing of perianal fistulae in most cases. The authors must be congratulated on publishing these findings. Negative findings provide much needed feedback on the effectiveness of treatment after introducing a new technique or pursuing new indications for a known technique. Radiofrequency thermocoagulation has become common practice as the primary treatment of varicose veins. Recently, new indications for the radiofrequency technique have been defined. For example, obliteration of the sinus in simple pilonidal disease with radiofrequency has been shown to be highly successful 2. We now know that pilonidal disease is caused by loose hairs entering the pits in the intergluteal cleft by their root ends, where a foreign body reaction creates the pilonidal sinus. Consequently, it is understandable that after removing the hairs from the pilonidal cavity, obliteration of the pits by thermocoagulation in order to avoid future potential ports of hair re-entry is a sound treatment principle. The pathophysiology of cryptoglandular and Crohn's fistulae has not been conclusively established. Crohn's disease is thought to be caused by a failure of the intestinal mucosal immune system to tolerate commensal bacteria. The highest healing rates in the featured study were achieved in patients with Crohn's disease (overall success 64 percent) 1. All these patients were on anti-tumour necrosis factor alpha therapy. There is now growing evidence that in patients with Crohn's fistulae, it is essential to combine surgery with biologic agents 2, 3. When managing Crohn's fistulae, combining a surgical procedure, which prevents entry of bacteria to the fistula, with immunotherapy seems to be the logical approach. The overall healing rate in patients with cryptoglandular fistulae was only 41% at 5 months follow-up 1. The persistent inflammation in the anal crypt is nowadays believed to occur as a result of a defective local immune system. Hence, before introduction of new surgical techniques, a better understanding of what process drives this ongoing perianal sepsis is recommended.

Immunomodulator use does not prevent first loss of response to anti-tumour necrosis factor alpha therapy in inflammatory bowel disease: long-term outcomes in a real-world cohort.

Recent prospective studies suggest combination therapy with immunomodulators improves efficacy, but long-term data is limited. To assess whether anti-tumour necrosis factor alpha (anti-TNF) monotherapy was associated with earlier loss of response (LOR) than combination therapy in a real-world cohort with long-term follow up. A retrospective audit was conducted of inflammatory bowel disease patients receiving anti-TNF therapy in a tertiary centre and specialist private practices. All patients with accurate data for anti-TNF commencement and adequate correspondence to determine end-points were included. Outcomes measured included time to first LOR, causes and biochemical parameters. Two hundred and twenty-four patients were identified; 139 (62.1%) on combination therapy and 85 (37.9%) on monotherapy. Forty-five percent of patients had LOR during follow up until a maximum of 8.5 years; 59.4% on combination therapy and 40.6% on monotherapy (P = 0.533). The median time to LOR was not different between groups; 1069 days for combination therapy and 1489 days for monotherapy (P = 0.533). There was no difference in time to LOR between patients treated with different combination regimens or different anti-TNF agents. In this large cohort of patients in a real-world setting, patients treated with anti-TNF monotherapy had similar rates of LOR as patients on anti-TNF combination therapy, at both short- and long-term follow up.

Long-term efficacy and tolerability of TNFα inhibitors in the treatment of non-infectious ocular inflammation: an 8-year prospective surveillance study

Background/AimTo report the efficacy and tolerability of antitumour necrosis factor-alpha therapy (TNF inhibitors [TNFi]) in the management of non-infectious ocular inflammation, including uveitis and scleritis, in adult patients over an...

Relative risk of tuberculosis in patients with rheumatic diseases managed with anti-tumour necrosis factor-alpha therapy: A nationwide cohort study.

Anti-tumour necrosis factor-alpha (anti-TNF-α) therapy is known to raise the risk of granulomatous infections, leading to development of risk management strategies at national or global level. This study aimed to determine the relative risk (RR) of tuberculosis (TB) due to anti-TNF-α usage in patients with rheumatologic diseases (RDs) in a nationwide basis. This retrospective cohort study included patients with rheumatoid arthritis (RA), ankylosing spondylitis, juvenile idiopathic arthritis or psoriatic arthritis (PsA) that treated with or without anti-TNF-α agents, as registered in the national prescription information system between years 2013 and 2015. Two-year RR of TB after anti-TNF-α therapy initiation was calculated in this RD population, including main subgroups. The study cohort included 413500 RD patients, where anti-TNF-α(+) arm (n=2117) had mean age of 41.9±13.4years and male distribution of 54.3%. Four patients among anti-TNF-α users developed TB compared to 128 patients in anti-TNF-α-naïve group (189 vs 31 cases per 100000 patients, respectively), yielding a 2-year RR of 6.07 (95% CI, 2.25-16.42) with an attributable risk of 0.16%. These RRs (95% CI), which were particularly pronounced, were 5.39 (1.69-7.17) in men, 6.12 (2.26-16.55) in adults, and 5.70 (1.41-23.08) in RA and 13.46 (1.58-114.40) in PsA patients. There was no difference between the anti-TNF-α users who developed and undeveloped TB regarding drug utilization characteristics, except significantly less immunosuppressive drug exposure in TB patients. This study is the first prescription-based nationwide study to suggest an elevated RR of TB in a comparably younger population with a broad spectrum of RDs managed with any approved anti-TNF-α drug in Turkey.

Genetic and expression changes in $$\hbox {TNF-}\upalpha $$ TNF- α as a risk factor for rheumatoid arthritis pathogenesis in northeast India

Antitumour necrosis factor-alpha (TNF-α) therapy is used as a clinical intervention for rheumatoid arthritis (RA) but differences exist in response to the treatment which makes the candidature of the screening of TNF-α alteration(s) at genetic and expression levels an important agenda prior to treatment. This study aims to determine the associative role of TNF-α -308G/A polymorphism and differential expression of TNF-α in the pathogenesis of RA. A case-control study where a total of 126 RA patients were enrolled based on ACR-EULAR (2010) criteria, along with 160 community matched age and sex controls over a period of three years. The differential expression level of TNF-α mRNA and protein level was studied and TNF-α -308G/A polymorphism was screened by T-ARMS PCR assay. All statistical analysis was performed using SPSS software. mRNA expression level of TNF-α was upregulated in RA cases (avg. 15.85 ± 9.52 fold) compared to control. TNF-α protein level was found to be higher in RA cases (28.62±7.17 pg/mL) compared to control (23.14±6.91 pg/mL). TNF-α -308 variant GA genotype was higher in RA (46.03%) than in control (25%). The presence of TNF-α -308 variant A allele was associated with increased risk of RA susceptibility (odds ratio (OR) = 2.559 at 95% confidence interval (CI), P< 0.001) but not severity (OR = 1.617 at 95% CI, P = 0.571). The presence of -308 variant genotype was associated with a higher TNF-α mRNA and protein expression. The presence of TNF-α -308A allele is associated with increased risk of RA susceptibility and differential TNF-α expression, and has prognostic significance. Association of higher TNF-α pro-inflammatory cytokine levels with northeast Indian patients makes them suitable subjects for anti-TNF-α therapy.

Vedolizumab exposure levels and clinical outcomes in ulcerative colitis: determining the potential for dose optimisation.

SummaryBackgroundProspectively designed studies assessing the exposure‐response profile of vedolizumab are lacking. Observational exposure‐response data for vedolizumab are limited and have not been adjusted for potential confounding factors, particularly those that may affect vedolizumab clearance.AimsTo (a) investigate the vedolizumab exposure‐response relationship after adjusting for potential confounding variables; (b) propose potential target serum vedolizumab concentrations for future study; (c) ascertain whether early vedolizumab serum concentrations were associated with short‐ and long‐term clinical outcomes in adults with ulcerative colitis in GEMINI 1.MethodsPropensity‐score‐based case‐matching analysis was performed using data from GEMINI 1 and an earlier large population pharmacokinetic study, with vedolizumab clearance or concentration as predictors of clinical remission and response, adjusted for age, weight, anti‐tumour necrosis factor alpha therapy history, serum albumin and faecal calprotectin concentrations. Potential vedolizumab concentration targets at weeks 6, 14 and steady state were proposed. Association between early vedolizumab concentrations at weeks 2, 4 and 6 and clinical remission at weeks 14 and 52 was evaluated.ResultsAmong 693 patients with pharmacokinetic data at week 6, potential target vedolizumab concentrations at weeks 6, 14 and steady state were 37.1, 18.4 and 12.7 µg/mL respectively. Week 6 was identified as the earliest time at which vedolizumab concentrations were consistently associated with clinical remission at weeks 14 and 52.ConclusionsIn this comprehensively adjusted analysis, vedolizumab concentrations at week 6 were associated with short‐ and long‐term remission. Potential induction and maintenance target concentrations were proposed for further study.

An explorative study on deep profiling of peripheral leukocytes to identify predictors for responsiveness to anti-tumour necrosis factor alpha therapies in ankylosing spondylitis: natural killer cells in focus

BackgroundTherapeutic targeting of tumour necrosis factor (TNF)-α is highly effective in ankylosing spondylitis (AS) patients. However, since one-third of anti-TNF-treated AS patients do not show an adequate clinical response there is an urgent need for new biomarkers that would aid clinicians in their decision-making to select appropriate therapeutic options. Thus, the aim of this explorative study was to identify cell-based biomarkers in peripheral blood that could be used for a pre-treatment stratification of AS patients.MethodsA high-dimensional, multi-parametric flow cytometric approach was applied to identify baseline predictors in 31 AS patients before treatment with the TNF blockers adalimumab (TNF-neutralisation) and etanercept (soluble TNF receptor).ResultsAs the major result, the frequencies of natural killer (NK) cells, and in particular CD8-positive (CD8+) NK cell subsets, were most predictive for therapeutic outcome in AS patients. While an inverse correlation between classical CD56+/CD16+ NK cells and reduction of disease activity was observed, the CD8+ NK cell subset behaved in the opposite direction. At baseline, responders showed significantly increased frequencies of CD8+ NK cells compared with non-responders.ConclusionsThis is the first study demonstrating that the composition of the NK cell compartment has predictive power for prediction of therapeutic outcome for anti-TNF-α blockers, and we identified CD8+ NK cells as a potential new player in the TNF-α-driven chronic inflammatory immune response of AS.

Cell-centred meta-analysis reveals baseline predictors of anti-TNFα non-response in biopsy and blood of patients with IBD

ObjectiveAlthough anti-tumour necrosis factor alpha (anti-TNFα) therapies represent a major breakthrough in IBD therapy, their cost–benefit ratio is hampered by an overall 30% non-response rate, adverse side effects and high...

Tubérculo coroideo asintomático en un paciente con enfermedad de Crohn en tratamiento con adalimumab

IntroductionAdalimumab, an anti-tumour necrosis factor alpha therapy for active Crohn's disease (CD), is associated with increased risks of tuberculosis infection. Case reportThe case is presented of a 48 year-old male with active CD on treatment with adalimumab. After three months, he developed a miliary pulmonary tuberculosis infection, with a solitary non-reactive choroidal tubercle temporal-superior to the optic disc being found in an ophthalmological study. Fluorescein angiography showed late hyperfluorescence in a staining pattern. Optic coherence tomography showed a flat mass without serous retinal detachment. The choroidal tubercle slowly regressed with antituberculosis therapy. DiscussionChoroidal tubercles with no vitreo-retinal symptomatology can be present in patients with CD and on treatment with adalimumab.

Surgical management of fistulating perianal Crohn's disease: a UK survey

Around one-third of patients with Crohn's disease are affected by Crohn's fistula-in-ano (pCD). It typically follows a chronic course and patients undergo long-term medical and surgical therapy. We set out to describe current surgical practice in the management of pCD in the UK. A survey of surgical management of pCD was designed by an expert group of colorectal surgeons and gastroenterologists. This assessed acute, elective, multidisciplinary and definitive surgical management. A pilot of the questionnaire was undertaken at the 2015 meeting of the Digestive Disease Federation. The survey was refined and distributed nationally through the trainee collaborative networks. National rollout obtained responses from 133 of 179 surgeons approached (response rate 74.3%). At first operation, 32% of surgeons would always consider drainage of sepsis and 31.1% would place a draining seton. At first elective operation, 66.6% would routinely insert of draining seton, and 84.4% would avoid cutting seton. An IBD multidisciplinary team was available to 87.6% of respondents, although only 25.1% routinely discussed pCD patients. Anti-tumour necrosis factor-alpha therapy was routinely considered by 64.2%, although 44.2% left medical management to gastroenterologists. Common definitive procedures were removal of the seton only (70.7%), fistulotomy (57.1%), advancement flap (38.9%), fistula plug (36.4%) and ligation of intersphincteric track (LIFT) procedure (31.8%). Indications for diverting stoma or proctectomy were intractable sepsis, incontinence and poor quality of life. This survey has demonstrated areas of common practice, but has also highlighted divergent practice including choices of definitive surgery and multimodal management. Practical guidelines are required to support colorectal surgeons in the UK.

P403 Golimumab therapy for ulcerative colitis – an Irish multicentre experience

Background: Golimumab (GLB) is a subcutaneous anti-tumour necrosis factor alpha (anti-TNF) therapy. Randomised controlled trials have demonstrated GLB efficacy in the induction and maintenance of remission in ulcerative colitis (UC). Data are few on the outcome of GLB therapy for UC in routine clinical practice. Aims: To describe the outcome of GLB therapy for UC in routine clinical practice in Ireland. Methods: Patients receiving GLB as therapy for UC were identified (n=77) from six Irish Medical centers. Only ambulatory outpatients, with 6 months of follow up post GLB initiation were included (n=69). Baseline clinical, demographic and laboratory data were collected. The primary endpoints were factors associated with durability of GLB response measured by time to drug discontinuation; 3-month clinical response; and 6-month corticosteroid free remission rates. Clinical response was defined as a decrease from baseline in partial Mayo score of at least 3 points and ongoing receipt of GLB. Clinical remission was defined as a partial Mayo score of less than or equal to 2 and continuing receipt of GLB. Secondary endpoints included rates of dose optimisation, dose intervention strategy and adverse events. Raw p values are reported with p values <0.006 (Bonferroni correction) considered significant Results: The study cohort comprised n=69 UC patients. Baseline characteristics were as follows (continuous variables, median [range]): Age 41.4 years [20.3–76.8]; 55% male; disease duration 6.5 years [0–29.9]; clinical Mayo subscore 6 [0–9]; proctitis, left-sided and extensive colitis in 8%, 54% and 38% respectively; baseline CRP 4.4 mg/L [0.2–134.6]; baseline albumin 42 g/L (16–51). Proportions on concomitant medications at GLB initiation were as follows: 5-aminosalicylate therapy 78%, concomitant immunomodulator 45%, systemic corticosteroids 40% (prednisolone dose, 35mg [5–40]). 36% of subjects were anti-TNF naive. Proportions receiving 50mg and 100mg 4-weekly maintenance regimes were 44% and 56% respectively. 3-month clinical response and 6-month corticosteroid free clinical remission rates were 42% and 42% respectively. 41% of patients required GLB dose optimisation (median [95% CI] time to dose optimisation: 6.5 months [1.4–11.6]); 44% dose increase and 56% interval shortening. Baseline CRP of ≥5mg/L is associated with a shorter time to GLB discontinuation, hazard ratio 3.1 (95% CI 1.4–6.7], p=0.005. Significant adverse events occurred in 3% of patients. Conclusions: These real world clinical data demonstrate GLB is an effective and safe induction and maintenance agent for UC. GLB dose optimisation is frequently required. A high baseline CRP, likely reflective of increased inflammatory burden, is associated with a less durable GLB response.

Neurosarcoidosis: a clinical approach to diagnosis and management

Sarcoidosis is a rare but important cause of neurological morbidity, and neurological symptoms often herald the diagnosis. Our understanding of neurosarcoidosis has evolved from early descriptions of a uveoparotid fever to include presentations involving every part of the neural axis. The diagnosis should be suspected in patients with sarcoidosis who develop new neurological symptoms, those presenting with syndromes highly suggestive of neurosarcoidosis, or neuro-inflammatory disease where more common causes have been excluded. Investigation should look for evidence of neuro-inflammation, best achieved by contrast-enhanced brain magnetic resonance imaging and cerebrospinal fluid analysis. Evidence of sarcoidosis outside the nervous system should be sought in search of tissue for biopsy. Skin lesions should be identified and biopsies taken. Chest radiography including high-resolution computed tomography is often informative. In difficult cases, fluorodeoxyglucose positron emission tomography and gallium-67 imaging may identify subclinical disease and a target for biopsy. Symptomatic patients should be treated with corticosteroids, and if clinically indicated other immunosuppressants such as hydroxychloroquine, azathioprine, cyclophosphamide or methotrexate should be added. Anti-tumour necrosis factor alpha therapies may be considered in refractory disease but caution should be exercised as there is evidence to suggest they may unmask disease.

Pigmented lichenoid drug eruption: a new clinical presentation of interface dermatitis induced by anti-TNF alpha drugs

Anti-tumour necrosis factor alpha (TNFα) therapies are used in several inflammatory diseases. A wide range of adverse events has been reported in patients receiving these agents, including lupus-like syndrome, lichen planus, or psoriasiform eruption [1], all comprising, histologically, a lichenoid interface dermatitis. It is commonly accepted that lichenoid eruptions are associated with increased expression of type I interferon (IFN) [2, 3]. Here, we report a novel clinical presentation of pigmented [...]

Ulcerative proctitis is a frequent location of paediatric-onset UC and not a minor disease: a population-based study

ObjectiveNatural history of paediatric-onset ulcerative proctitis (UP) is poorly described. Our aim was to describe the phenotype and disease course of incident UP in a population-based study of paediatric-onset UC.Patients...