Comparative Risk of Serious Infection With Vedolizumab vs Anti-Tumor Necrosis Factor in Inflammatory Bowel Disease : Results From Nationwide Swedish Registers

INTRODUCTION: We aimed to assess the risk of serious infection in patients with inflammatory bowel disease (IBD) treated with vedolizumab compared with those treated with anti-tumor necrosis factors (TNF) and the general population.METHODS: In this Swedish cohort study, treatment episodes were identified from nationwide health registers. We used Cox regression with propensity score-matched cohorts to estimate hazard ratios (HRs) for incident serious infections, defined as infections requiring hospital admission.RESULTS: During 1,376 treatment episodes in Crohn's disease, the rate of serious infections per 100 person-years (PY) was 5.18 (95% CI = 3.98-6.63) with vedolizumab vs 3.54 (95% CI = 2.50-4.85) with anti-TNF; HR = 1.72 (95% CI = 1.12-2.65), partly explained by more gastrointestinal infections. Compared with the rate of 0.75/100 PY (95% CI = 0.59-0.92) in a matched general population cohort, vedolizumab demonstrated higher risk (HR = 7.00; 95% CI = 5.04-9.72). During 1,294 treatment episodes in ulcerative colitis, the corresponding rates were 3.74/100 PY (95% CI = 2.66-5.11) with vedolizumab vs 3.42/100 PY (95% CI = 2.31-4.89) with anti-TNF; HR = 0.80 (95% CI = 0.47-1.36) during the initial 1.1 years and HR = 2.03 (95% CI = 0.65-6.32) after 1.1 years (truncated due to nonproportional hazards). Pneumonia accounted for 40% of all infections among anti-TNF, whereas no case was observed among vedolizumab episodes. Compared with the rate of 0.69/100 PYs (95% CI = 0.53-0.87) in a matched general population cohort, vedolizumab showed an HR of 5.45 (95% CI = 3.67-8.11).DISCUSSION: Vedolizumab was associated with increased risks of serious infections compared with anti-TNF in Crohn's disease but not in ulcerative colitis. Nonetheless, the panorama of serious infections seemed to differ between the drugs. Our findings underscore the importance of clinical awareness of infections and the safety profile of the 2 therapies.</p

Histologic Remission in Inflammatory Bowel Disease and Female Fertility [Elektronisk resurs] : A Nationwide Study

Background & Aims: Inflammatory bowel disease (IBD) is linked to reduced female fertility, but it is unclear how fertility rates vary by histologic disease activity. Methods: Nationwide IBD cohort of Swedish women aged 15 to 44 years. We examined fertility rates during periods with vs without histologic inflammation (n = 21,046; follow-up, 1990–2016) and during periods with vs without clinical activity (IBD-related hospitalization, surgery, or treatment escalation) (n = 24,995; follow-up, 2006–2020). Accounting for sociodemographics and comorbidities, we used Poisson regression to estimate adjusted fertility rate ratios (aFRRs) for live births conceived during 12-month periods of histologic inflammation (vs histologic remission) and 3-month periods of clinically active IBD (vs quiescent IBD). Results: During periods with vs without histologic inflammation, there were 6.35 (95% confidence interval [CI], 5.98–6.73) and 7.09 (95% CI, 6.48–7.70) live births conceived per 100 person-years of follow-up, respectively, or 1 fewer child per 14 women with 10 years of histologic inflammation (aFRR, 0.90; 95% CI, 0.81–1.00). In women with histologic inflammation, fertility was similarly reduced in ulcerative colitis (UC) (aFRR, 0.89 [95% CI, 0.78–1.02]) and Crohn's disease (CD) (aFRR, 0.86 [95% CI, 0.72–1.04]). Clinical IBD activity was associated with an aFRR of 0.76 (95% CI, 0.72–0.79) or 1 fewer child per 6 women with 10 years of clinical activity. Fertility was reduced in clinically active UC (aFRR, 0.75 [95% CI, 0.70–0.81]) and CD (aFRR, 0.76 [95% CI, 0.70–0.82]). Finally, among women with clinically quiescent IBD, histologic inflammation (vs histologic remission) was associated with reduced fertility (aFRR, 0.85 [95% CI, 0.73–0.98]). Conclusions: An association between histologic and clinical activity and reduced female fertility in CD and UC was found. Notably, histologic inflammation was also linked to reduced fertility in women with clinically quiescent IBD

Histological remission in inflammatory bowel disease and risk of adverse pregnancy outcomes : A nationwide study

Background: Inflammatory bowel disease (IBD) has been linked to adverse pregnancy outcomes, but it is unclear how risks vary by histological activity. Methods: We performed a nationwide study of Swedish women diagnosed with IBD 1990–2016 and a pre-pregnancy (<12 months) colorectal biopsy with vs. without histological inflammation (1223 and 630 births, respectively). We also examined pregnancy outcomes in 2007–2016 of women with vs. without clinically active IBD (i.e., IBD-related hospitalization, surgery, or medication escalation) <12 months before pregnancy (2110 and 4993 births, respectively). Accounting for smoking, socio-demographics, and comorbidities, generalized linear models estimated adjusted risk ratios (aRRs) for preterm birth (<37 gestational weeks) and small-for-gestational age (SGA, <10th percentile weight for age). Findings: Of infants to women with vs. without histological inflammation, 9.6% (n = 117) and 6.5% (n = 41) were preterm, respectively (aRR = 1.46; 95%CI = 1.03–2.06). Histological inflammation was associated with preterm birth in ulcerative colitis (UC) (aRR = 1.64; 95%CI = 1.07–2.52), especially extensive colitis (aRR = 2.37; 95%CI = 1.12–5.02), but not in Crohn's disease (aRR = 0.99; 95%CI = 0.55–1.78). Of infants to women with vs. without histological inflammation, 116 (9.6%) and 56 (8.9%), respectively, were SGA (aRR = 1.09; 95%CI = 0.81–1.47). Clinically active disease before pregnancy was linked to preterm birth (aRR = 1.42; 95%CI = 1.20–1.69), but not to SGA birth (aRR = 1.13; 95%CI = 0.96–1.32). Finally, of infants to women without clinical activity, histological inflammation was not significantly associated with preterm birth (aRR = 1.20; 95%CI = 0.68–2.13). Interpretation: Histological and clinical activity in IBD, especially in UC, were risk factors for preterm birth. Further research is needed to determine the importance of pre-pregnancy histological activity in women without clinically-defined disease activity. Funding: The Swedish Society of Medicine

Capturing biologic treatment for IBD in the Swedish Prescribed Drug Register and the Swedish National Patient Register–a validation study

Background: It is not known to what extent biologic treatment for IBD is captured in the Swedish Prescribed Drug Register (PDR) and the National Patient Register (NPR). Methods: A cross-sectional study from July 2005 until 2017, comparing data on biologic treatment in the PDR and the NPR with medical records. We assessed the proportion of started treatment episodes in the medical records that were found in the PDR/NPR ever, within +/− one year and within +/− three months; for any biologic drug, per specific drug (infliximab, adalimumab, golimumab, vedolizumab, ustekinumab), by calendar period (2005–2008, 2009–2012, and 2013–2017) and by study center. For adalimumab, we assessed the validity of end of treatment episodes. Results: Medical records of 1361 patients and 2323 treatment episodes with any biologic were reviewed and 80.1% (95% CI: 78.4–81.7) were ever captured in the PDR/NPR in. A time window of +/− one year or +/− three months reduced the sensitivity to 63.3% (95% CI: 61.3–65.3) and 52.6% (95% CI: 50.5–54.6), respectively. The sensitivity was high (>85%) for the prescribed injection drugs adalimumab, golimumab, and ustekinumab for all time windows and for adalimumab end of treatment, while considerably lower for the infusion drugs infliximab and vedolizumab. Conclusions: The PDR and the NPR are reliable data sources on treatment with injection biologics in patients with IBD in Sweden. Infliximab and vedolizumab are poorly captured, why PDR/NPR data should only be used after careful consideration of their limitations or complemented by other data sources, e.g., the disease-specific quality register SWIBREG

Association Between Inflammatory Bowel Disease and Spondyloarthritis: Findings from a Nationwide Study in Sweden

Background and aims: Inflammatory bowel disease [IBD] has been associated with spondyloarthritis [SpA], but population-based estimates are scarce. Here we compare the occurrence of SpA before and after a diagnosis of IBD with the general population, overall and by IBD subtype and age. Methods: We used a nationwide register-based cohort study of 39 203 patients diagnosed with IBD during 2006-2016, identified from Swedish registers and gastrointestinal biopsy data, and 390 490 matched reference individuals from the general population. Conditional logistic regression models were used to estimate odds ratios [ORs] for a prior [prevalent] SpA diagnosis and conditional Cox regression to calculate hazard ratios [HRs] for a subsequent [incident] SpA diagnosis in IBD patients. Results: IBD patients were more likely to have prevalent SpA at IBD diagnosis [2.5%] compared with reference individuals [0.7%] with an OR of 3.48 [95% CI: 3.23, 3.75]. They also more often received an incident diagnosis of SpA; during 23 341 934 person-years of follow-up in IBD patients, there were 1030 SpA events [5.0/1000 person-years] compared with 1524 SpA events in the reference group [0.72/1000 person-years], corresponding to an HR of 7.15 [95% CI: 6.60, 7.75]. In subgroup analyses, associations were most pronounced among patients with Crohn's disease ([OR = 5.20; 95% CI: 4.59, 5.89], and [HR = 10.55; 95% CI: 9.16, 12.15]) and paediatric onset IBD ([OR = 3.63; 95% CI: 2.35, 5.59] and [HR = 15.03; 95% CI: 11.01, 20.53]). Conclusions: IBD patients more frequently experience SpA both before and after the diagnosis of IBD compared with the general population, supporting evidence of a shared pathophysiology. The variation in SpA comorbidity, across IBD subtypes and age groups, calls for targeted approaches to facilitate timely diagnosis and intervention

Tumour necrosis factor inhibitors in Crohns disease and the effect on surgery rates

Aim Surgery is an important therapeutic option for Crohns disease. The need for first bowel surgery seems to have decreased with the introduction of tumour necrosis factor inhibitors (TNFi; adalimumab or infliximab). However, the impact of TNFi on the need for intestinal surgery in Crohns disease patients irrespective of prior bowel resection is not known. The aim of this work is to compare the incidence of bowel surgery in Crohns disease patients who remain on TNFi treatment versus those who discontinue it. Method We performed a nationwide register-based observational cohort study in Sweden of all incident and prevalent cases of Crohns disease who started first-line TNFi treatment between 2006 and 2017. Patients were categorized according to TNFi treatment retention less than or beyond 1 year. The study cohort was evaluated with regard to incidence of bowel surgery from 12 months after the first ever TNFi dispensation. Results We identified 5003 Crohns disease patients with TNFi exposure: 3748 surgery naive and 1255 with bowel surgery prior to TNFi initiation. Of these patients, 7% (n = 353) were subjected to abdominal surgery during the first 12 months after the start of TNFi and were subsequently excluded from the main analysis. A majority (62%) continued TNFi for 12 months or more. Treatment with TNFi for less than 12 months was associated with a significantly higher surgery rate compared with patients who continued on TNFi for 12 months or more (hazard ratio 1.26, 95% CI 1.09-1.46; p = 0.002). Conclusion Treatment with TNFi for less than 12 months was associated with a higher risk of bowel surgery in Crohns disease patients compared with those who continued TNFi for 12 months or more.Funding Agencies|Bengt Ihre Research Fellowship; Stockholm County Council ALFStockholm County Council [20180565, 20170720, 20190638]; SFO Young Scholar Award at Karolinska Institutet; Swedish Research CouncilSwedish Research CouncilEuropean Commission [2020-02002]; Swedish Society of Medicine; Bengt Ihre Fellowship; Stockholm County Council postdoctoral fellowship; Bengt Ihre Foundation</p

The Risk of Serious Infections Before and After Anti-TNF Therapy in Inflammatory Bowel Disease : A Retrospective Cohort Study

BACKGROUND: Serious infections have been observed in patients with inflammatory bowel disease (IBD) on anti-TNF use-but to what extent these infections are due to anti-TNF or the disease activity per se is hard to disentangle. We aimed to describe how the rates of serious infections change over time both before and after starting anti-TNF in IBD.METHODS: Inflammatory bowel disease patients naïve to anti-TNF treatment were identified at 5 centers participating in the Swedish IBD Quality Register, and their medical records examined in detail. Serious infections, defined as infections requiring in-patient care, the year before and after the start of anti-TNF treatment were evaluated.RESULTS: Among 980 patients who started their first anti-TNF therapy between 1999 and 2016, the incidence rate of serious infections was 2.19 (95% CI,1.43-3.36) per 100 person years the year before and 2.11 (95% CI, 1.33-3.34) per 100 person years 1 year after treatment start. This corresponded to an incidence rate ratio 1 year after anti-TNF treatment of 0.97 (95% CI, 0.51-1.84). Compared with before anti-TNF therapy, the incidence of serious infection was significantly decreased more than 1 year after treatment (incidence rate ratio 0.56; 95% CI, 0.33-0.95; P = .03).CONCLUSIONS: In routine clinical practice in Sweden, the incidence rate of serious infection among IBD patients did not increase with anti-TNF therapy. Instead, serious infections seemed to decrease more than 1 year after initiation of anti-TNF treatment

Clinical effectiveness of golimumab in ulcerative colitis : a prospective multicentre study based on the Swedish IBD Quality Register, SWIBREG

Objectives Clinical trials demonstrated that golimumab is effective in anti-TNF naive patients with ulcerative colitis. We aimed to assess the clinical effectiveness of golimumab in a real-world setting. Materials and methods This was a prospective cohort study, conducted at 16 Swedish hospitals. Data were collected using an electronic case report form. Patients with active ulcerative colitis, defined as Mayo endoscopic subscore &amp;gt;= 2 were eligible for inclusion. The primary outcomes were clinical effectiveness at 12 weeks and 52 weeks, i.e. response (defined as a decrease in Mayo score by &amp;gt;= 3 points or 30% from baseline) and remission (defined as a Mayo score of &amp;lt;= 2 with no individual subscores &amp;gt;1). Results Fifty patients were included. At study entry, 70% were previously exposed to anti-TNF, 16% to vedolizumab, and 96% to immunomodulators. The 12 and 52-week drug continuation rates were 37/50 (74%) and 23/50 (46%), respectively. The 12-week response rate was 14/50 (28%), the remission rate, 8/50 (16%) and the corresponding figures at week 52 were 13/50 (26%) and 10/50 (20%). Among patients who continued golimumab, the median Mayo score decreased from 7 (6-9) at baseline to 1 (0-5) at 52 weeks (p &amp;lt; .01) and the faecal calprotectin decreased from 862 (335-1759) mu g/g to 90 (34-169) mu g/g (p &amp;lt; .01). Clinical response at week 12 was highly predictive of clinical remission at week 52 (adjusted OR: 73.1; 95% CI: 4.5-1188.9). Conclusions The majority of golimumab treated patients represented a treatment refractory patient-group. Despite this, our results confirm that golimumab is an effective therapy in ulcerative colitis.Funding Agencies|MSD; Swedish governments agreement on medical training and research [OLL-836791, OLL-929900]</p

Inflammatory Bowel Disease, Periconceptional Disease Activity, and Risk of Major Congenital Anomalies : A Nationwide Cohort Study

INTRODUCTION: It is uncertain whether the risk of major congenital anomalies (mCAs) is increased in children of women with inflammatory bowel disease (IBD).METHODS: We aimed to determine the risk of mCAs in a Swedish nationwide cohort of 13,131 singleton live births from 1997 to 2020 to women with IBD and 61,909 matched children to women without IBD from the general population. We additionally examined mCAs according to periconceptional histological inflammation (vs remission: 1,124 and 646 births, respectively) or clinically active IBD (vs quiescent: 3,380 and 6,603 births, respectively). Adjusted risk ratios (aRRs) for overall and organ-specific mCAs were estimated using generalized linear models. These models adjusted for maternal sociodemographics, comorbidities, body mass index, and smoking.RESULTS: There were 38.0 (n = 499) mCAs per 1,000 births to women with IBD vs 33.9 (n = 2,101) in matched comparators and a risk difference of 1 extra mCA per 246 births to women with IBD (aRR 1.11; 95% confidence interval [CI] 1.01-1.23). Risks of heart defects and mCAs of the urinary system partly drove estimates. The risk of mCAs was similar in children of women with ulcerative colitis and Crohn's disease. Periconceptional histological inflammation (vs remission) or clinically active (vs quiescent) IBD did not further influence the risk of mCA in the child (aRR 0.87 [95% CI 0.55-1.40] and aRR 1.04 [95% CI 0.85-1.27], respectively).DISCUSSION: Children of women with IBD had a heightened susceptibility to mCAs, although absolute and relative risks were lower than previously reported. IBD activity was not linked to mCA risks, but those analyses included relatively few events.</p