Emerging treatments for ulcerative colitis: a systematic review

Objectives: Various investigational medicinal products have been developed for ulcerative colitis (UC). Our aim was to systematically evaluate novel pharmacological therapeutic agents for the treatment of UC.

Material and methods: Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations were followed. A search of the medical literature was conducted in the MEDLINE database for original research papers published between 01 January 2010 and 31 October 2014.

Results: Twenty one studies, including 11,524 adults were analyzed. Thirteen different novel therapeutic drug options were identified. Vedolizumab and golimumab were superior to placebo as induction and maintenance therapy. Tofacitinib showed dose related efficacy for induction therapy. Etrolizumab showed higher clinical remission rates compared to placebo. Phosphatidylcholine led to an improved clinical activity index. HMPL-004 may become a mesalamine alternative for mild to moderate UC. PF00547,659 was well tolerated. Statins were not beneficial for acute exacerbations of UC. Abatacept, rituximab and visilizumab did not lead to improved outcomes compared to placebo. Higher concentration of BMS 936557 was associated with improved efficacy compared to placebo. Basiliximab did not enhance corticosteroid efficacy.

Conclusions: Patients with UC might achieve clinical response or remission by utilizing some of these agents with a favorable side effect profile. Further studies are needed to evaluate their short- and long-term efficacy and safety.     

Serum interleukin-6 level is associated with response to infliximab in ulcerative colitis

Objectives: Infliximab is effective in patients with ulcerative colitis (UC); however, one-third of patients do not respond and require additional therapies such as other biologic agents. Therefore, the aim of this study was to analyze the association between pro-inflammatory molecules and clinical efficacy to elucidate possible mechanisms for the non-response to infliximab to aid in treatment selection.

Materials and method: Patients with moderate-to-severe active UC receiving infliximab in our hospital between 2010 and 2016 for whom pre-treatment serum samples were available were retrospectively evaluated. We analyzed the association between serum interleukin (IL)-6, tumor necrosis factor-α (TNF-α) and soluble mucosal vascular addressin cell adhesion molecule-1 (sMAdCAM-1) and the clinical efficacy of infliximab. The primary endpoint was clinical response at the end of the induction period.

Results: Forty-one patients were included in this study. After induction therapy, 27 patients (65.9%) showed a clinical response. Serum IL-6 levels were significantly lower in responders than in non-responders (p?=?.012), whereas no significant differences were noted in other factors including sMAdCAM-1 and TNF-α. Multivariate analysis identified that serum IL-6 level (odds ratio?=?0.72; 95% confidence interval, 0.54–0.96; p?=?.027) was independently associated with response to infliximab.

Conclusions: Serum IL-6 level is associated with response to infliximab in UC. Elevated concentrations of IL-6 may provide insight to the mechanism of non-response to infliximab.     

Comparison of golimumab 100-mg monotherapy to golimumab 50 mg plus methotrexate in patients with rheumatoid arthritis: Results from a multicenter,cohort study

Objective. The aim of this study was to compare the efficacy and safety of golimumab (GLM) 50 mg + methotrexate (MTX) combination therapy and GLM 100 mg monotherapy in patients with rheumatoid arthritis (RA).

Methods. The subjects were 115 RA patients (92 females and 23 males; median (range) age, 64 (17–87) years; median (range) disease duration, 8 (0.6–48) years) started on GLM. Eighty-three patients received GLM 50 mg/4 weeks + MTX (C group; median (range) MTX dosage 8 (2–16) mg/week), and 32 patients received GLM 100 mg/4 weeks (M group).

Serum C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), matrix metalloproteinase-3, disease activity score (DAS) 28-ESR, DAS28-CRP, simplified disease activity index, and clinical disease activity index were evaluated 4, 12, and 24 weeks after starting GLM.

Results. There were no significant differences in disease activity, adverse events, and drug continuation rates at 24 weeks between the groups. The DAS28-ESR remission rate was 34% in the C group and 26% in the M group.

Conclusions. GLM 100 mg monotherapy improved disease activity as well as GLM 50 mg + MTX combination therapy. GLM 100 mg monotherapy appears to have a sufficient therapeutic effect in RA patients who cannot take MTX.     

Long-term effects and colectomy rates in ulcerative colitis patients treated with infliximab: A Danish single center experience

Abstract

Objective. Infliximab (IFX) is a well-established treatment for both acute, severe ulcerative colitis (UC) and chronic, refractory UC. However, data on the long-term clinical outcome and colectomy rates after IFX treatment in a routine clinical setting are sparse. The aim of this study was to provide further data on the long-term effect of IFX for acute, severe and chronic, refractory UC in unselected patients treated at a single center. Material and Methods. A retrospective analysis of all patients (n = 52) treated with IFX for UC before February 2009 was performed. The material comprised 19 patients (37%) with acute, severe UC and 33 patients (63%) with chronic, refractory UC. The primary outcome was colectomy rate; the secondary outcome clinical response. Results. The overall colectomy rate was 27% (14/52 patients) after a median follow-up of 22 months (range 4–57 months). The colectomy rate was 37% (7/19 patients) in the group with acute, severe UC and 21% (7/33 patients) among those with chronic, refractory UC. In all, 77% of the patients had clinical response to IFX treatment with no difference between the two subgroups. Among those with an initial clinical response, 50% (20/40 patients) had sustained clinical response. Conclusion. IFX is of long-term benefit as rescue treatment in selected patients with acute, severe UC with about two-thirds of the patients avoiding colectomy. The beneficial effect on colectomy rate in chronic, refractory UC seems less convincing although these patients may still achieve a sustained clinical response.     

Effectiveness of adalimumab for the treatment of ulcerative colitis in clinical practice: comparison between anti-tumour necrosis factor-naïve and non-naïve patients

Background

Ulcerative colitis (UC) treatment is focused to achieve mucosal healing, avoiding disease progression. The study aimed to evaluate the real-world effectiveness of adalimumab (ADA) in UC and to identify predictors of remission to ADA.

Methods

This cohort study used data from the ENEIDA registry. Clinical response, clinical remission, endoscopic remission, adverse events (AE), colectomy, and hospitalisations were evaluated; baseline characteristics and biological parameters were compared to determine predictors of response.

Results

We included 263 patients (87 naïve and 176 previously exposed to anti-tumour necrosis factor alpha, TNF). After 12 weeks, clinical response, clinical remission, and endoscopic remission rates were 51, 26, and 14 %, respectively. The naïve group demonstrated better response to treatment than the anti-TNF-exposed group at short-term. Clinical and endoscopic remission within 1 year of treatment was better in the naïve group (65 vs. 49 and 50 vs. 35 %, respectively). The rates of AE, dose-escalation, hospitalisations, and colectomy during the first year were higher in anti-TNF-exposed patients (40, 43, and 27 % vs. 26, 21, and 11 %, respectively). Patients with primary failure and intolerance to the first anti-TNF and severe disease were associated with worse clinical response. Primary non-response to prior anti-TNF treatment and severe disease were predictive of poorer clinical remission. Low levels of C-reactive protein (CRP) and faecal calprotectin (FC) at baseline were predictors of clinical remission.

Conclusions

In clinical practice, ADA was effective in UC, especially in anti-TNF naïve patients. FC and CRP could be predictors of treatment effectiveness.

     

A prospective cohort study to assess the relevance of vedolizumab drug level monitoring in IBD patients

Background: Vedolizumab (VDZ) drug monitoring strategies in inflammatory bowel disease (IBD) patients have not been systematically investigated so far. We evaluated the correlation between VDZ trough levels (VTL) and the treatment response in IBD.

Methods: Fifty-one patients with active IBD on or starting a therapy with VDZ were enrolled in this prospective and observational single centre study. Disease activity indices, blood tests, and anthropometric parameters were assessed over a time period of 6 months. One hundred and fifty-five VDZ serum trough levels were measured directly before the next scheduled application using liquid chromatography mass spectrometry (LC-MS/MS).

Results: VDZ treatment was found to be clinically effective (Harvey Bradshaw Index (HBI) dropping from 10 to 5.5 points (p?p?p?=?.00153). UC patients with haemoglobin levels higher 12?g/dl at the time of VTL measurement had significantly higher VTL compared to patients with lower haemoglobin levels (35.4 versus 15.6 µg/ml, p?Conclusions: Our data suggest a significant correlation between VTL and response to therapy in IBD patients (higher VTL associated with better response).     

Serum 1,3-beta-D-glucan as a noninvasive test to predict histologic activity in patients with inflammatory bowel disease

BACKGROUND 1,3-beta-D-glucan(BG)is a ubiquitous cell wall component of gut microorganisms.We hypothesized that the serum levels of BG could reflect active intestinal inflammation in patients with inflammatory bowel disease.AIM To determine whether the serum BG concentrations correlate with intestinal inflammation.METHODS A prospective observational study was performed in a tertiary referral center,from 2016 to 2019,in which serum BG was determined in 115 patients with Crohn’s disease(CD),51 with ulcerative colitis(UC),and 82 controls using a photometric detection kit.Inflammatory activity was determined by ileocolonoscopy,histopathology,magnetic resonance enterography,and biomarkers,including fecal calprotectin(FC),C-reactive protein,and a panel of cytokines.The ability of BG to detect active vs inactive disease was assessed using the area under the receiver operating characteristic curve.In subgroup analysis,serial BG was used to assess the response to therapeutic interventions.RESULTS The serum BG levels were higher in CD patients than in controls(P=0.0001).The BG levels paralleled the endoscopic activity in CD patients and histologic activity and combined endoscopic and histologic activity in both CD and UC patients.The area under the curve(AUC)in receiver operating characteristic analysis to predict endoscopic activity was 0.694[95%confidence interval(CI):0.60-0.79;P=0.001]in CD,and 0.662(95%CI:0.51-0.81;P=0.066)in UC patients.The AUC in receiver operating characteristic analysis to predict histologic activity was 0.860(95%CI:0.77-0.95;P<0.001)in CD,and 0.786(95%CI:0.57-0.99;P=0.015)in UC patients.The cut-off values of BG for both endoscopic and histologic activity were 60μg/mL in CD,and 40μg/mL in UC patients.Performance analysis showed that the results based on BG of 40 and 60μg/mL were more specific for predicting endoscopic activity(71.8%and 87.2%for CD;and 87.5%and 87.5%for UC,respectively)than FC(53.3%and 66.7%for CD;and 20%and 80%for UC,respectively);and also histologic activity(60.5%and 76.3%for CD;and 90.0%and 95.0%for UC,respectively)than FC(41.7%and 50.0%for CD;and 25%and 50%for UC,respectively).Regarding the clinical,endoscopic,and histologic activities,the BG levels were reduced following therapeutic intervention in patients with CD(P<0.0001)and UC(P=0.003).Compared with endoscopic(AUC:0.693;P=0.002)and histologic(AUC:0.868;P<0.001)activity,no significant correlation was found between serum BG and transmural healing based on magnetic resonance enterography(AUC:0.576;P=0.192).Positive correlations were detected between BG and IL-17 in the CD(r:0.737;P=0.001)and the UC group(r:0.574;P=0.005),and between BG and interferon-gamma in the CD group(r:0.597;P=0.015).CONCLUSION Serum BG may represent an important novel noninvasive approach for detecting mucosal inflammation and therapeutically monitoring inflammatory bowel diseases,particularly in CD.     

Short- and long-term efficacy of adalimumab salvage therapy after failure of calcineurin inhibitors in steroid-refractory ulcerative colitis

Objective: Calcineurin inhibitors are highly effective in patients with corticosteroid-refractory ulcerative colitis (UC). When therapy with calcineurin inhibitors fails, adalimumab can be considered to avoid colectomy. The efficacy and safety of this sequential alternative salvage therapy remain unknown. Therefore, the present study was performed to investigate the short- and long-term efficacy and safety of adalimumab after failure of calcineurin inhibitors in corticosteroid-refractory UC.

Materials and methods: Patients with a corticosteroid-refractory flare of UC who did not respond to calcineurin inhibitors and received continuing salvage therapy with adalimumab were included in this retrospective, observational, single-centre study. The cumulative rates of colectomy were calculated using the Kaplan–Meier method. Clinical remission and response were evaluated based on the Rachmilewitz index. The cumulative rates of colectomy were calculated. Predictive factors for clinical remission and colectomy were identified. In the safety evaluation, any adverse event occurring after the administration of adalimumab was considered.

Results: Forty-one patients were enrolled; 78% had extensive colitis and 87% had moderate to severe colitis. Seventeen patients (41%) underwent colectomy during the follow-up period. At week 8, 26, and 52 after adalimumab injection, 27%, 39%, and 32% of patients achieved clinical remission, respectively. The adverse event rate was 17%, including one case of tuberculosis.

Conclusions: The efficacy of adalimumab for calcineurin inhibitor-refractory UC was examined for the first time. Treatment with adalimumab avoided the need for colectomy in two-thirds of patients with corticosteroid-refractory UC in whom calcineurin inhibitors had failed. However, attention is needed to avoid adverse events, especially infection.     

Granulocyte/monocyte adsorptive apheresis for the treatment of therapy-refractory chronic active ulcerative colitis

Objectives: Current options for patients with steroid-dependent, chronic-active ulcerative colitis (UC) with insufficient response/intolerance to immunosuppressants (ISs) and/or biologics are limited. The aim of this study was to assess the long-term outcome of granulocyte/monocyte adsorptive (GMA) apheresis (Adacolumn^®) in this population.

Materials and methods: Ninety five adults with steroid-dependent active UC and insufficient response/intolerance to IS and/or TNF inhibitors received 5–8 aphereses in a single induction series of ≤10 weeks. Endpoints included rates of remission (clinical activity index [CAI]?≤?4) at weeks 24 and 48.

Results: Of 94 patients (ITT population), remission and response rates were 34.0% and 44.7% at week 24, and 33.0% and 39.4% at week 48. Among 30 patients with prior failure of IS and biologics, 33.3% and 20.0% were in remission at weeks 24 and 48. At both weeks, 19.2% of patients achieved steroid-free remission. Sustained remission or response occurred in 27.7% of patients at 48 weeks. The cumulative colectomy rate at week 96 was 23.4%. Safety was consistent with previous findings.

Conclusions: This study confirms findings of the 12-week interim analysis and demonstrates that GMA apheresis provides a safe and beneficial long-term outcome for patients with chronic active UC resistant/intolerant to IS and/or TNF inhibitors.     

Clinical monitoring: infliximab biosimilar CT-P13 in the treatment of Crohn’s disease and ulcerative colitis

Objective: The infliximab biosimilar CT-P13 (Remsima^®, Inflectra^®) was approved in Europe for the treatment of inflammatory bowel disease (IBD) based on extrapolation of data from patients with rheumatic disease. Because there are limited published reports on clinical outcomes for IBD patients treated with CT-P13, we monitored responses to induction treatment with this biosimilar in patients with Crohn’s disease (CD) or ulcerative colitis (UC) in centres across the Czech Republic.

Material and methods: Fifty-two patients with CD (n?=?30) or UC (n?=?22) were treated with 5?mg/kg CT-P13 for up to 14 weeks. Effectiveness of therapy was evaluated with the Crohn’s Disease Activity Index (CDAI) or the Mayo Scoring System (MSS) in patients with CD or UC, respectively, before and after 14 weeks. Additional goals were to evaluate weight changes, serum C-reactive protein (CRP) levels, and complications/adverse events.

Results: In patients with CD, remission (CDAI?<150) was achieved in 50.0% of cases, and partial response (≥70-point decrease in CDAI score from baseline) in the remaining 50.0%. In patients with UC, remission (total score on partial Mayo index?≤2 points) was achieved in 40.9% of cases, partial response (≥2-point decrease in partial Mayo score from baseline) in 54.5%, and no response in 4.5%. There were statistically significant improvements in CDAI, MSS and CRP serum levels after 14 weeks of therapy, and body weight increased. Four adverse events were identified (n?=?1 each): lower-extremity phlebothrombosis, herpes labialis, pneumonia and allergic reaction.

Conclusions: This prospective observational study provides evidence of the effectiveness of CT-P13 in IBD.     

Assessing adherence to objective disease monitoring and outcomes with adalimumab in a real-world IBD cohort

BackgroundData suggests that tight objective monitoring may improve clinical outcomes in IBD.AimTo assess the adherence to serial tight objective monitoring(clinical and biomarkers) and its effect on clinical outcomes.MethodsWe retrospectively reviewed the chart of 428 consecutive IBD patients started on adalimumab between January 1,2015–January 1,2019 [338 Crohn's disease(CD), 90 ulcerative colitis(UC)]. Clinical symptoms(assessed by Harvey-Bradshaw-Index,partial Mayo),C-Reactive Protein(CRP), and fecal calprotectin(FCAL) assessments were captured at treatment initiation and at 3,6,9, and12 months. Dose optimization and drug sustainability curves were plotted by Kaplan-Meier method.ResultsClinical evaluation was available in nearly all patients at 3(CD-UC:95–94%), 6(90–83%), 9(86–85%) and 12(96–89%) months. CRP testing frequency decreased in CD patients over time. Compliance to serial FCAL testing was low. Clinical remission at one-year was higher in patients adherent to early assessment visit at 3 months(p = 0.001 for CD and UC). Adherence to early follow-up resulted in earlier dose optimization in CD and UC patients(pLogrank=0.026 for UC & p = 0.09 for CD). Overall drug sustainability did not differ.ConclusionClinical & CRP, but not FCAL, were frequently assessed in patients starting adalimumab. Adherence to early objective combined follow-up visits resulted in earlier dose optimization, improved one-year clinical outcomes but did not change drug sustainability.     

Postmarketing surveillance evaluating the safety and effectiveness of golimumab in Japanese patients with rheumatoid arthritis

Objectives: The purpose of this study was to evaluate the real-world safety and effectiveness of golimumab (GLM) in Japanese patients with rheumatoid arthritis.

Methods: A postmarketing surveillance of 5154 patients was conducted with a follow-up duration of at least 24 weeks. Patients were divided into four groups based on the initial treatment: 50?mg or 100?mg of GLM with concomitant use of methotrexate (MTX) and 50?mg or 100?mg of GLM monotherapy. Patient characteristics at baseline, safety and effectiveness were assessed for each group.

Results: Over 70% of patients received 50?mg of GLM with concomitant MTX, and approximately, 20% received monotherapy. The incidence rate of adverse events was 45.40 per 100 patient-years. The incidence of adverse events including serious adverse events was comparable across all groups. The proportion of patients showing remission or low disease activity increased from 13.69% to 46.21% at the final evaluation, and no differences were observed in the percentage of remission across the four groups. Concomitant MTX use was associated with higher probability of continuing therapy.

Conclusions: GLM showed effectiveness in Japanese rheumatoid arthritis patients with an acceptable safety profile.     

Impact of infliximab therapeutic drug level monitoring on outcomes of patients with inflammatory bowel disease: A real-world experience from a Middle Eastern cohort

Background and study aimTherapeutic drug monitoring (TDM) through measurement of infliximab (IFX) trough levels and antibodies to infliximab (ATI) is performed to guide IFX intensification strategies and improve its efficacy. We conducted this study to explore the relationship between clinical and endoscopic/radiological remission and IFX and ATI levels in patients with inflammatory bowel disease (IBD) treated with IFX and to evaluate the appropriateness of treatment decision post TDM.Patients and methodsThis was a cross-sectional study of a cohort of adult patients with IBD. Serum IFX trough concentrations and ATI were measured.ResultsA total of 129 patients [104] with ulcerative colitis (UC) and 25 with Crohn’s disease (CD)] were included in this study, of whom 61.2% were men. The mean disease duration was 6.7 years, and 72% of patients with UC had extensive colitis. The mean serum IFX trough level was 4.1 µg/mL; the IFX trough levels were subtherapeutic in 75 patients (58%), therapeutic in 37 patients (29%), and supratherapeutic in 17 patients (13%). Positivity to ATI was found in 16 patients (12.4%). Only 43 patients (33.3%) underwent an appropriate change in therapy after TDM, patients with penetrating CD disease had low IFX levels and higher C-reactive protein levels at 12 months before TDM.ConclusionsPatients with IBD with therapeutic IFX levels tend to have increased endoscopic/radiological remission rates. However, an appropriate change in management based on TDM was absent in the majority of patients, potentially reflecting the need to have a dashboard to support and guide clinicians in decision-making.     

Incidence and Clinical Outcomes of Inflammatory Bowel Disease in South Korea, 2011–2014: A Nationwide Population-Based Study

Background

The incidence of inflammatory bowel disease (IBD) is increasing in East Asia; however, population-based data from this region are lacking.

Aim

We conducted a nationwide, population-based study to examine the incidence and disease course of IBD in South Korea.

Methods

Using the National Health Insurance claims data, we collected data on patients diagnosed with IBD [10,049 with ulcerative colitis (UC) and 5595 with Crohn’s disease (CD)] from 2011 to 2014.

Results

During the study period, the average annual incidence of UC was 5.0 per 10⁵, while that of CD was 2.8 per 10⁵. Among patients with UC, the cumulative rates of surgery 1 and 4 years after diagnosis were 1.0 and 2.0%; those among patients with CD were 9.0 and 13.9%, respectively. The 1- and 4-year cumulative rates of moderate- to high-dose corticosteroid use were, respectively, 26.6 and 45.2% among patients with UC, and 29.9 and 50.8% among those with CD. Similarly, the 1- and 4-year cumulative rates of immunomodulator use were 14.1 and 26.4% among patients with UC, and 58.3 and 76.1% among those with CD, respectively. With regard to biologic use, the 1- and 4-year cumulative rates were 3.0 and 9.0% among patients with UC, and 11.1 and 31.7% among those with CD, respectively.

Conclusions

The recent incidence of IBD in South Korea has been the highest in East Asia. Patients who had been diagnosed recently with IBD showed lower rates of surgery and higher rates of immunomodulator and biologic use compared to those reported ever in South Korea.

     

Sustained clinical benefit,improved quality of life,and reduced intestinal surgery from maintenance infliximab treatment in inflammatory bowel disease*

Abstract

Objectives: Anti-TNF treatment is established for patients with severe inflammatory bowel disease (IBD) refractory to conventional medication. However, long-term real-life observations are limited. We have monitored 200 patients with primary response to infliximab (Remicade^®).

Methods: Patients with either Crohn’s disease (CD) or ulcerative colitis (UC) who started IFX and had clinical response at 1?year were prospectively followed. C-reactive protein (CRP), albumin, fecal calprotectin (FCP), Harvey Bradshaw index (HBI) in CD cases, and Quality of Life index were monitored. Concomitant medications, surgery and hospitalisation were assessed.

Results: Out of the 200 patients, 164 suffered from CD. Median disease duration was 5.0 (0.2–44.0) years and the observation time was 3.4 (1.0–13.9) years. Steroid use was reduced from 51% to 10%. HBI in CD patients decreased from 8.0?±?0.40 to 2.7?±?0.26. Disease activity in UC patients was only assessed by biochemical markers. CRP decreased from 29.0?±?6.2 to 8.0?±?7.1?mg/L. FCP showed a decrease from 1918 (1837) to 191 (646) mg/kg. Hospitalization showed similar tendency and quality of life was improved. Twenty-seven percent had been operated before IFX introduction compared to 11% during the observation period. Loss of response was seen in 42 patients, of which 20 patients needed intestinal surgery.

Conclusion: Two-thirds of the patients demonstrated stable clinical benefit from maintenance IFX. The results show steroid-sparing efficacy as well as improved quality of life and reduced need for surgery.     

Adalimumab trough serum levels and anti-adalimumab antibodies in the long-term clinical outcome of patients with Crohn’s disease

Objective: Few data are available on the relevance of adalimumab (ADA) trough serum levels and anti-ADA antibodies (AAA) during long-term follow-up of patients with Crohn’s Disease (CD), and their association with disease outcome. In this study, our aim was to assess ADA trough serum levels and the presence of AAA according to disease activity and clinical response during long-term follow-up in a series of patients with CD treated with ADA monotherapy.

Material and methods: We prospectively evaluated 23 consecutive, infliximab-naïve CD patients who achieved clinical remission/response after induction and were in maintenance treatment with ADA, and who were followed-up for at least 72 weeks. Blood samples were drawn at standardized time points to assess ADA through levels, AAA.

Results: At week 48, we found significantly (p?=?0.027) different ADA trough serum levels in patients in remission (10.1?mcg/mL), mild (7.4?mcg/mL), and moderate/severe disease (4.5?mcg/mL). Median ADA trough levels were significantly lower in patients with AAA (3.7?mcg/mL versus 9.3?mcg/mL, p?=?0.006). At the end of follow-up (median 102 weeks, range 73–112 weeks), ADA trough serum concentrations were significantly higher (11.9?mcg/mL) as compared to patients with mild and moderate/severe disease (5.5?mcg/mL, p?=?0.0002). Furthermore, median ADA trough concentrations showed a trend towards lower levels in AAA positive patients (5.2?mcg/mL versus 7.2?mcg/mL, p?=?0.371).

Conclusions: Our results emphasize the relevance of therapeutic drug monitoring in CD patients on biologic treatment. ADA trough serum levels and the presence of AAA are important features in the management of patients on ADA treatment.     

Assessment of the effectiveness of golimumab 50-mg and 100-mg regimens in patients with rheumatoid arthritis in daily practice

Abstract

Objectives. To assess the effectiveness of the golimumab (GLM) 50-mg and 100-mg regimens in patients with rheumatoid arthritis (RA) in daily practice. Methods. We retrospectively analyzed RA patients who started GLM between September 2011 and July 2012. Patients were divided into three groups: a 50-mg group; a 50/100-mg group (had a dose increase to 100 mg); and a 100-mg group (started GLM at 100 mg). We assessed Disease Activity Score 28 (DAS28) and treatment continuation rate. Risk factors associated with time to discontinuation of the 50-mg regimen were determined with proportional hazards analysis. Results. We analyzed 74 patients: 43 in the 50-mg group, 23 in the 50/100-mg group, and 8 in the 100-mg group. DAS28 improved from 4.0 ± 1.0, 4.8 ± 1.0, and 4.7 ± 1.9, respectively, at baseline to 2.4 ± 1.2, 3.3 ± 1.5, and 2.5 ± 0.7, respectively, at week 52. Treatment continuation rates at week 52 were 73.7%, 60.9%, and 87.5%, respectively. In the 50/100-mg group, the mean DAS28 improved significantly from 4.4 ± 1.2 before to 3.6 ± 1.3 12 weeks after the dose increase. Oral corticosteroid therapy ≥ 5 mg/day, previous use of two biologic agents, and DAS28 > 5.1 at initiation of GLM were significantly associated with discontinuation of the 50-mg regimen. Conclusions. Both GLM 50-mg and 100-mg regimens are effective in patients with RA in daily practice.     

Health‐related quality of life in patients with inflammatory bowel disease five years after the initial diagnosis

Background: Health‐related quality of life (HRQOL) has become an important tool in evaluating patient satisfaction in inflammatory bowel disease (IBD). So far, few prospective follow‐up studies have been done to identify variables that influence HRQOL. We aimed to identify demographic and clinical variables that influence HRQOL 5 years after diagnosis in patients with ulcerative colitis (UC) or Crohn disease (CD) included in a prospective follow‐up study from 1990 to 1994 (the IBSEN study). Methods: All patients completed the Inflammatory Bowel Disease Questionnaire (IBDQ), a disease‐specific quality‐of‐life questionnaire translated into Norwegian and validated. We present data from 497 patients (328 UC patients and 169 CD patients, mean age 43.3 years, 48% female). The impact of age, gender, smoking, symptom severity, disease distribution, rheumatic symptoms and surgery on IBD patients' HRQOL was analysed. Results: Women had a reduction in IBDQ total score of 10 points compared to men, CD patients had a reduction of 7.5 compared to UC patients. The patients with moderate/severe symptoms had a 50 points lower score than the patients without symptoms. The patients with rheumatic symptoms had a 10 points lower total score than the patients without these symptoms. All differences were statistically significant. The multiple regression analysis showed that symptom severity, rheumatic symptoms and female gender were the strongest predictors of reduction in HRQOL for both diagnosis groups. Conclusion: IBD symptoms, rheumatic symptoms and female gender have a significant influence on patients' HRQOL as measured by IBDQ. This was confirmed by the regression analysis.     

Long-term outcome of inflammatory bowel disease patients with deep remission after discontinuation of TNFα-blocking agents

Background: Little data exist on the long-term prognosis of patients with inflammatory bowel disease (IBD) after stopping TNFα-blocking therapy in deep remission. Existing data indicate that approximately 50% of patients on combination therapy who discontinued TNFα-blockers are still in remission 24 months later. The aims of this follow-up analysis were to evaluate the long-term remission rate after cessation of TNFα-blocking therapy, the predicting factors of a relapse and the response to restarting TNFα blockers.

Methods: The first follow-up data of 51 IBD patients (17 Crohn’s disease [CD], 30 ulcerative colitis [UC] and four inflammatory bowel disease type unclassified [IBDU]) in deep remission at the time of cessation of TNFα-blocking therapy have been published earlier. The long-term data was collected retrospectively after the first follow-up year to evaluate the remission rate and risk factors for the relapse after a median of 36 months.

Results: After the first relapse-free year, 14 out of the remaining 34 IBD patients relapsed (41%; 5/12 [42%] CD and 9/22 [41%] UC/IBDU). Univariate analysis indicated no associations with any predictive factors. Re-treatment was effective in 90% (26/29) of patients.

Conclusion: Of IBD patients in deep remission at the time of cessation of TNFα-blocking therapy, up to 60% experience a clinical or endoscopic relapse after a median follow-up time of 36 months (95% CI 31–41 months). No individual risk factors predicting relapse could be identified. However, the initial response to a restart of TNFα-blockers seems to be effective and well tolerated.     

Algorithms to facilitate shared decision-making for the management of mild-to-moderate ulcerative colitis

ABSTRACT

Introduction: Nonadherence has been a key barrier to the efficacy of medical treatments in ulcerative colitis (UC). Engaging patients in their IBD care via shared decision-making (SDM) to facilitate self-management may improve adherence to therapy.

Areas covered: This review aims to summarize the most recent trial evidence from 2012 to 2017 for mild-to-moderate UC in order to develop clinical algorithms that guide SDM to facilitate self-management. A structured literature search via multiple electronic databases was performed using the search terms ‘ulcerative colitis,’ ‘treatment,’ ‘management,’ ‘medication,’ ‘maintenance,’ ‘remission,’ ‘5-ASA,’ and ‘inflammatory bowel disease.

Expert commentary: Novel formulations of existing oral and topical medications have expanded the treatment options available for the induction and maintenance therapy for mild-to-moderate UC. Daily dosing of 5-ASA therapy is equivalent to twice daily dosing. The combination therapies of oral plus topical 5-ASA therapy and 5-ASA plus corticosteroid therapy are more effective than monotherapy. Budesonide MMX now plays a role in the management of mild-to-moderate UC. This review collates the evidence on drug efficacy and safety, adherence and tolerability, and noninvasive monitoring of mild-to-moderate UC into SDM-orientated algorithms to facilitate self-management.