Summary: Background: Anti‐TNFα agents have revolutionised management of chronic inflammatory diseases. Paradoxically, these agents might provoke development of de novo autoimmune diseases.Aim: To examine whether there is an increased risk of developing Crohn's disease (CD) and ulcerative colitis (UC) while under treatment with anti‐TNFα agents for diseases other than inflammatory bowel disease (IBD)Methods: A nationwide cohort study, based on Danish health registries, of all patients who utilised anti‐TNFα agents for non‐IBD indications. Included were patients, who had diseases for which anti‐TNFα agent is indicated (rheumatoid arthritis, psoriasis/psoriatic arthritis, ankylosing spondylitis, others). The observation period for development of de novo IBD started from 2004. Exposed patients had received at least one dose of anti‐TNFα.Results: In total 17 018 individuals with autoimmune diseases were exposed to anti‐TNFα (the vast majority had infliximab, etanercept and adalimumab), and 63 308 individuals were not. Patients treated with etanercept had an increased risk of being diagnosed with CD and UC while under treatment, adjusted hazard ratio 2.0 [95% CI: 1.4‐2.8] and 2.0 [95% CI: 1.5‐2.8], respectively. The corresponding hazards ratios for infliximab were 1.3 [95% CI: 0.8‐2.2] and 1.0 [95% CI:0.6‐1.6], and for adalimumab 1.2 [95% CI: 0.8‐1.8] and 0.6 [95% CI: 0.3‐1.0].Conclusions: Patients treated for autoimmune diseases with anti‐TNFα had an increased risk of being diagnosed with CD or UC while under treatment with etanercept. The nature of this association is uncertain. This finding has relevance to clinical care and insights into common mechanisms of the pathophysiology of these diseases.

Objective To examine the chance of live births and adverse birth outcomes in women with ulcerative colitis (UC) and Crohn's disease (CD) compared with women without inflammatory bowel disease (IBD) who have undergone assisted reproductive technology (ART) treatments. Methods This was a nationwide cohort study based on Danish health registries, comprising all women with an embryo transfer during 1 January 1994 through 2013. The cohorts comprised 1360 ART treatments in 432 women with UC, 554 ART treatments in 182 women with CD and 148 540 treatments in 52 489 women without IBD. Our primary outcome was live births per ART treatment cycle. We controlled for multiple covariates in the analyses. Our secondary outcomes were adverse birth outcomes. Results The chance of a live birth for each embryo transfer was significantly reduced in ART treatments in women with UC (OR=0.73, 95% CI 0.58 to 0.92), but not significantly reduced in the full model of ART treatments in women with CD (OR=0.77, 95% CI 0.52 to 1.14). Surgery for CD before ART treatment significantly reduced the chance of live birth for each embryo transfer (OR=0.51, 95% CI 0.29 to 0.91). In children conceived through ART treatment by women with UC, the OR of preterm birth was 5.29 (95% CI 2.41 to 11.63) in analyses including singletons and multiple births; restricted to singletons the OR was 1.80, 95% CI 0.49 to 6.62. Conclusions Our results suggest that women with UC and CD receiving ART treatments cannot expect the same success for each embryo transfer as other infertile women. Women with CD may seek to initiate ART treatment before needing CD surgery. Increased prenatal observation in UC pregnancies after ART should be considered.

Objectives: Methods: Results: Conclusions:

Objectives No studies have examined the efficacy of assisted reproductive technology (ART) treatment in women with rheumatoid arthritis. Therefore, we examined the chance of live birth after ART treatment in women with rheumatoid arthritis compared with women without rheumatoid arthritis. Methods Our cohort study is based on nationwide Danish health registries, comprising all women with an embryo transfer during 1 January 1994 through 30 June 2017. The cohorts comprised 1149 embryo transfers in women with rheumatoid arthritis, and 198 941 embryo transfers in women without rheumatoid arthritis. Our outcome was live birth per embryo transfer, and we controlled for multiple covariates in the analyses. In subanalyses, we examined a chance of biochemical/clinical pregnancy after ART and a possible impact of corticosteroid use prior to embryo transfer. Results The adjusted OR (aOR) for a live birth per embryo transfer in women with rheumatoid arthritis, relative to women without rheumatoid arthritis, was 0.78 (95% CI 0.65 to 0.92). The aORs for biochemical and clinical pregnancies were 0.81 (95% CI 0.68 to 0.95) and 0.82 (95% CI 0.59 to 1.15), respectively. Corticosteroid prescription prior to embryo transfer increased the OR for live birth (aOR=1.32 (95% CI 0.85 to 2.05)). Conclusions The chance of a live birth was significantly reduced in women with rheumatoid arthritis receiving ART treatment, relative to women without rheumatoid arthritis, and our result suggested that the problem was related to an impaired chance of embryo implantation. The role of corticosteroid use prior to embryo transfer must be a subject for further research.

Objective Information on the safety of paternal use of azathioprine (AZA) and 6-mercaptopurine (6-MP) prior to conception is limited. Based on nationwide data from the Danish health registries, we examined the association between paternal use of AZA/6-MP within 3 months before conception and adverse birth outcomes. Design This nationwide cohort study is based on data from all singletons born in Denmark from 1 January 1997 through 2013. Children fathered by men who used AZA/6-MP within 3 months before conception constituted the exposed cohort (N=699), and children fathered by men who did not use AZA/6-MP 3 months prior to conception constituted the unexposed cohort (N=1 012 624). The outcomes were congenital abnormalities (CAs), preterm birth and small for gestational age (SGA). We adjusted for multiple covariates and performed a restricted analysis of men with IBD. Results There were no significantly increased risks of CAs, preterm birth or SGA in exposed versus unexposed cohorts of children. The adjusted ORs were 0.82 (95% CI 0.53 to 1.28) for CAs, 1.17 (95% CI 0.72 to 1.92) for preterm birth and 1.38 (95% CI 0.76 to 2.51) for SGA. Restricting our analysis to fathers with IBD showed similar results with no significantly increased risk of adverse birth outcomes. Conclusions This nationwide study is the largest to date, examining the effect of preconceptual paternal use of AZA/6-MP on birth outcomes in live born singletons. The results of no significantly increased risks of adverse birth outcomes are reassuring and support the continuation of paternal AZA/6-MP treatment during conception.

Men with inflammatory bowel disease (IBD) may have decreased sexual function due to factors related to the underlying disease, medication, and/or surgery. We aimed to examine the use of erectile dysfunction (ED) medications in men with IBD. This is a nationwide cohort study based on the Danish registries, comprising all men >18 years old with IBD during 1 January 1995 through December 2016. The cohorts included 31,498 men with IBD and 314,980 age-matched men without IBD. Our main outcome was a first prescription of an ED medication. Cox regression analyses were used to estimate the hazard rate (HR) for use of ED medications, controlled for multiple time-varying covariates. Overall, 21,966 (69.7%) men had ulcerative colitis (UC) while 9532 (30.3%) had Crohn’s disease (CD). Men with a first ED prescription numbered 3749 (11.9%) (men with IBD) and 30,635 (9.7%) (men without IBD). Adjusting for central nervous system and intestinal anti-inflammatory medications, systemic corticosteroids and co-morbidities, the HR was 1.19 (95% CI: 1.13–1.26) (IBD and no prior IBD operation), and 1.31 (95% CI: 1.20–1.43) (IBD and prior IBD operation). The adjusted HR for UC was 1.17 (95% CI: 1.10–1.24) (no operation) and 1.43 (95% CI: 1.27–1.61) (prior operation), and for CD 1.26 (95% CI: 1.15–1.38) (no operation) and 1.20 (95% CI: 1.06–1.35) (prior operation). Men with IBD are more likely to fill an ED prescription than men without IBD. This result is significant regardless of a history of IBD surgery.