Expanding eligibility and improving quality of cervical cancer screening in Estonia: The 2021 reforms.

Estonia has one of the highest death rates from cervical cancer in the European Union despite having had a population-based screening programme for over 15 years. In 2021, this high disease burden, alongside a new national cancer prevention plan, prompted a series of cervical cancer screening programme reforms to address low screening uptake and evidence of variable screening test quality. The reforms had three main elements: expansion of eligibility to all women aged 30-65 regardless of insurance status; increasing test provision by enabling family physicians to take screening samples and introducing self-sampling; and improving testing procedures, replacing cytology with HPV testing as the primary screening test. Although the impact of these changes is yet to be seen, early signs suggest increased programme participation. However, at 51 %, further action to address barriers to uptake will likely be necessary. If Estonia is to avoid another period of policy dormancy, as happened between 2006 and 2021, greater clarity on screening programme accountability is required. The establishment of the National Cancer Screening Group may enable this. The first test will be the delivery of an end-to-end evaluation of the reformed programme, with an emphasis on equity of access. The next step will be to develop and deliver solutions that respond to these needs.

Post-traumatic stress disorders in women victims-survivors of intimate partner violence: a mixed-methods pilot study in a French coordinated structure.

OBJECTIVES: This study aimed to examine the prevalence of post-traumatic stress disorder (PTSD) in victims-survivors of intimate partner violence (IPV) consulting at the specialised and original facility 'Maison des Femmes' (MdF) or in two close municipal health centres (MHCs). DESIGN: A mixed-methods study using a convergent parallel design from July 2020 to June 2021. SETTING/PARTICIPANTS: A questionnaire was proposed to women aged 18 years and over having suffered from IPV, in the MdF and in two MHCs. We also conducted qualitative interviews with a subsample of the women, asking for victim-survivors' perceptions of the effect of the MdF's care. PRIMARY AND SECONDARY OUTCOME MEASURES: The presence of a PTSD using the PTSD self-report checklist of symptoms, possibility of reaching women by phone 6 months after the inclusion visit, level of self-rated global health, number of emergency visits in the past 6 months, substances use, readiness to change and safety behaviours. RESULTS: A total of 67 women (mean age: 34 years (SD=9.7)) responded to our questionnaire. PTSD diagnosis was retained for 40 women (59.7%). Around 30% of participants self-rated their global health as bad. Less than 30% (n=18) of women were regular smokers, and only 7.5% of participants had a problematic alcohol use (Alcohol Use Disorders Identification Test-Consumption score ≥4), 19.4% women used psychotropic drugs. Six months after inclusion, half of participants had been reached by phone. Analysis of the qualitative interviews clarified victim-survivors' perceptions of the MdF's specific care: social networking, multidisciplinary approach, specialised listening, healthcare facilities, evasion and 'feeling at home'. CONCLUSIONS: The high prevalence of PTSD at inclusion was nearly the same between the three centres. This mixed-methods comparison will serve as a pilot study for a larger comparative trial to assess the long-term impact of the MdF's specialised care on victims-survivors' mental health, compared with the care of uncoordinated structures. TRIAL REGISTRATION NUMBER: NCT04304469.

Experience and expectations of pharmacogenetic tests in France.

Although French genomic medicine is reaching a turning point in its history and the implementation of genome sequencing in routine is being implemented as part of the France Genomic Medicine 2025 Plan (FGMP), many questions about secondary data management remain to be addressed. In particular, the use of pharmacogenetic (PGx) information that can be extracted from genome data is a concern. We sought to analyze the opinion of French health professionals on their desire to have access to this information. For this purpose, we created a 22-item questionnaire on the experiences, attitudes, expectations, and knowledge of French physicians and pharmacists about PGx. We collected the responses in different groups and determined a knowledge score with the last 3 questions of the questionnaire. Then, we built a prediction model for this score and determined which factors may influence it. Half of the responders were physicians (158/311) and the other half were pharmacists (153/311), and the majority of them worked in a hospital (265/311). Almost two third (62.7%, 195/311) of the responders thought that pharmacogenetic data should be communicated with genomic results for the primary indication within the framework of FGMP, and 89.1% (277/311) of them that PGx tests could be an interesting tool to optimize patients' drug therapy in the future. Only 11.2% (35/311) of the responders reached the maximum knowledge score, while 25.4% (76/311) had already prescribed or recommended a PGx test. This study identified a need for training for French physicians and pharmacists in PGx, particularly given the interest of health professionals in it.

Efficiency and effectiveness of intensive multidisciplinary follow-up of patients with stroke/TIA or myocardial infarction compared to usual monitoring: protocol of a pragmatic randomised clinical trial. DiVa (Dijon vascular) study.

INTRODUCTION: The ongoing ageing population is associated with an increase in the number of patients suffering a stroke, transient ischaemic attack (TIA) or myocardial infarction (MI). In these patients, implementing secondary prevention is a critical challenge and new strategies need to be developed to close the gap between clinical practice and evidence-based recommendations. We describe the protocol of a randomised clinical trial that aims to evaluate the efficiency and effectiveness of an intensive multidisciplinary follow-up of patients compared with standard care. METHODS AND ANALYSIS: The DiVa study is a randomised, prospective, controlled, multicentre trial including patients >18 years old with a first or recurrent stroke (ischaemic or haemorrhagic) or TIA, or a type I or II MI, managed in one of the participating hospitals of the study area, with a survival expectancy >12 months. Patients will be randomised with an allocation ratio of 1:1 in two parallel groups: one group assigned to a multidisciplinary, nurse-based and pharmacist-based 2-year follow-up in association with general practitioners, neurologists and cardiologists versus one group with usual follow-up. In each group for each disease (stroke/TIA or MI), 430 patients will be enrolled (total of 1720 patients) over 3 years. The primary outcome will be the incremental cost-utility ratio at 24 months between intensive and standard follow-up in a society perspective. Secondary outcomes will include the incremental cost-utility ratio at 6 and 12 months, the incremental cost-effectiveness ratio at 24 months, reduction at 6, 12 and 24 months of the rates of death, unscheduled rehospitalisation and iatrogenic complications, changes in quality of life, net budgetary impact at 5 years of the intensive follow-up on the national health insurance perspective and analysis of factors having positive or negative effects on the implementation of the project in the study area. ETHICS AND DISSEMINATION: Ethical approval was obtained and all patients receive information about the study and give their consent to participate before randomisation. Results of the main trial and each of the secondary analyses will be submitted for publication in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Identifier: NCT04188457. Registered on 6 December 2019.

Women and health professionals' perspectives on a conditional cash transfer programme to improve pregnancy follow-up: a qualitative analysis of the NAITRE randomised controlled study.

OBJECTIVES: Women of low socioeconomic status have been described as having suboptimal prenatal care, which in turn has been associated with poor pregnancy outcomes. Many types of conditional cash transfer (CCT) programmes have been developed, including programmes to improve prenatal care or smoking cessation during pregnancy, and their effects demonstrated. However, ethical critiques have included paternalism and lack of informed choice. Our objective was to determine if women and healthcare professionals (HPs) shared these concerns. DESIGN: Prospective qualitative research. SETTING: We included economically disadvantaged women, as defined by health insurance data, who participated in the French NAITRE randomised trial assessing a CCT programme during prenatal follow-up to improve pregnancy outcomes. The HP worked in some maternities participating in this trial. PARTICIPANTS: 26 women, 14 who received CCT and 12 who did not, mostly unemployed (20/26), and - 7 HPs. INTERVENTIONS: We conducted a multicentre cross-sectional qualitative study among women and HPs who participated in the NAITRE Study to assess their views on CCT. The women were interviewed after childbirth. RESULTS: Women did not perceive CCT negatively. They did not mention feeling stigmatised. They described CCT as a significant source of aid for women with limited financial resources. HP described the CCT in less positive terms, for example, expressing concern about discussing cash transfer at their first medical consultation with women. Though they emphasised ethical concerns about the basis of the trial, they recognised the importance of evaluating CCT. CONCLUSIONS: In France, a high-income country where prenatal follow-up is free, HPs were concerned that the CCT programme would change their relationship with patients and wondered if it was the best use of funding. However, women who received a cash incentive said they did not feel stigmatised and indicated that these payments helped them prepare for their baby's birth. TRIAL REGISTRATION NUMBER: NCT02402855.

Role of the endoscopic Doppler probe in nonvariceal upper gastrointestinal bleeding: Systematic review and meta-analysis.

OBJECTIVES: The effectiveness of the Doppler endoscopic probe (DEP) remains unclear in nonvariceal upper gastrointestinal bleeding (NVUGIB). We thus performed a systematic review characterizing the effectiveness of DEP in patients with NVUGIB addressing this question. METHODS: A literature search was done until July 2021 using MEDLINE, EMBASE, and ISI Web of Science. A series of meta-analyses were performed assessing outcomes among observational and interventional studies for DEP signal positive and negative lesions as well as DEP-assisted versus standard endoscopies. The primary outcome was "overall rebleeding"; secondary outcomes included all-cause mortality, bleeding-related mortality, need for surgery, length of stay, intensive care unit stay, and angiography. RESULTS: Fourteen studies were included from 1911 citations identified. Observational studies compared bleeding lesions with DEP-positive versus DEP-negative signals (11 studies, n = 800 prehemostasis; five studies, n = 148 with posthemostasis data). Three interventional studies (n = 308) compared DEP-assisted to standard endoscopy management. DEP signal positive versus negative lesions either prior to or following any possible hemostasis were at greater risk of overall rebleeding (odds ratio [OR] 6.54 [2.36, 18.11] and OR 25.96 [6.74, 100.0], respectively). The use of DEP during upper endoscopy significantly reduced overall rebleeding rates (OR 0.27 [0.14, 0.54]). When removing outcomes analysis for which only one study was available, all evaluable outcomes were improved with DEP characterization of management guidance except for all-cause mortality. CONCLUSION: Although with low certainty evidence, DEP-related information improves on sole visual prediction of rebleeding in NVUGIB, with DEP-guided management yielding decreased overall rebleeding, bleeding-related mortality, and need for surgery.

Combined incentive actions, focusing on primary care professionals, to improve cervical cancer screening in women living in socioeconomically disadvantaged geographical areas: a study protocol of a hybrid cluster randomised effectiveness and implementation trial- RESISTE.

INTRODUCTION: Cervical cancer (CC) causes thousands of deaths each year. Nearly 100% of cases are caused by oncogenic strains of human papillomavirus (HPV). In most industrialised countries, CC screening (CCS) is based on the detection of HPV infections. For many reasons including lower adherence to CCS, underserved women are more likely to develop CC, and die from it. We aim to demonstrate that the use of incentives could improve screening rates among this population. METHODS AND ANALYSIS: Our cluster randomised, controlled trial will include 10 000 women aged 30-65 years eligible for CCS, living in deprived areas in four French departments, two mainlands and two overseas, and who did not perform physician-based HPV testing within the framework of the nationally organised screening programme. HPV self-sampling kit (HPVss) will be mailed to them. Two interventions are combined in a factorial analysis design ending in four arms: the possibility to receive or not a financial incentive of €20 and to send back the self-sampling by mail or to give it to a health professional, family doctor, gynaecologist, midwife or pharmacist. The main outcome is the proportion of women returning the HPVss, or doing a physician-based HPV or pap-smear test the year after receiving the HPVss. 12-month follow-up data will be collected through the French National Health Insurance database. We expect to increase the return rate of HPV self-samples by at least 10% (from 20% to 30%) compared with the postal return without economic incentive. ETHICS AND DISSEMINATION: Ethics approval was first obtained on 2 April 2020, then on July 29 2022. The ethics committee classified the study as interventional with low risk, thus no formal consent is required for inclusion. The use of health insurance data was approved by the Commission Nationale Informatique et Libertés on 14 September 2021 (ref No 920276). An independent data security and monitoring committee was established. The main trial results will be submitted for publication in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: NCT04312178.

Association between Obstetric Complications and Intravitreal Anti-Vascular Endothelial Growth Factor Agents or Intravitreal Corticosteroids.

This nationwide population-based cohort study aimed to describe the use of intravitreal injections (IVTs) of anti-vascular endothelial growth factor (anti-VEGF) agents and corticosteroids in pregnant women in France and to report on the incidence of obstetric and neonatal complications. All pregnant women in France who received any anti-VEGF or corticosteroid IVT during pregnancy or in the month preceding pregnancy from 1 January 2009 to 31 December 2018 were identified in the national medico-administrative databases. Between 2009 and 2018, there were 5,672,921 IVTs performed in France. Among these IVTs, 228 anti-VEGF or corticosteroid IVTs were administered to 139 women during their pregnancy or in the month preceding their pregnancy. Spontaneous abortion or the medical termination of pregnancy occurred in 10 women (16.1%) who received anti-VEGF agents and in one (3.1%) of the women who received corticosteroids (p = 0.09). This is the first national cohort study of pregnant women treated with anti-VEGF or corticosteroid IVTs. We found a high incidence of obstetric complications in pregnant women treated with anti-VEGF or corticosteroid IVTs but could not demonstrate a statistically significant association between the intravitreal agents and these complications. These agents should continue to be used with great caution in pregnant women.

An update on drug-drug interactions associated with proton pump inhibitors.

INTRODUCTION: Proton pump inhibitors (PPIs) block the gastric H/K-ATPase, therefore inhibiting acid gastric secretion, leading to an increased pH (>4). They account for an extremely high number of prescriptions worldwide. Numerous drug-drug interactions have been described with PPIs, but all the described interactions do not have clinical significance. AREAS COVERED: This review will discuss the latest updates on drug-drug interactions with PPIs, focusing on the last 10-year publications in the following areas: anti-infective agents, anticancer drugs, antiplatelet agents and anticoagulants, and antidiabetics. EXPERT OPINION: Although pharmacokinetic interactions of PPIs have been described with many drugs, their clinical relevance remains controversial. However, given the extremely high number of people being treated with PPIs, clinicians should remain vigilant for interactions that may be clinically significant and require dose adjustment or therapeutic monitoring. Interestingly, not all PPIs have the same pharmacokinetic and pharmacodynamic profile, with some having a strong potential to inhibit CYP2C19, such as omeprazole, esomeprazole, and lansoprazole, while others, pantoprazole, rabeprazole, and dexlansoprazole, are weak CYP2C19 inhibitors. These may be preferred depending on co-prescribed treatments.In addition, new formulations have been developed to prevent some of the gastric pH-dependent drug interactions and should be evaluated in further large-scale prospective comparative studies.

Review article: obesity and colorectal cancer.

BACKGROUND: Obesity is a growing global public health problem. More than half the European and North American population is overweight or obese. Colon and rectum cancers are still the second leading cause of cancer death worldwide, and epidemiological data support an association between obesity and colorectal cancers (CRCs). AIM: To review the literature on CRC epidemiology in obese subjects, assessing the effects of obesity, including childhood or maternal obesity, on CRC, diagnosis, management, and prognosis, and discussing targeted prophylactic measures. METHOD: We searched PubMed for obesity/overweight/metabolic syndrome and CRC. Other key words included 'staging', 'screening', 'treatment', 'weight loss', 'bariatric surgery' and 'chemotherapy'. RESULTS: In Europe, about 11% of CRCs are attributed to overweight and obesity. Epidemiological data suggest that obesity is associated with a 30%-70% increased risk of colon cancer in men, the association being less consistent in women. Visceral fat or abdominal obesity seems to be of greater concern than subcutaneous fat obesity, and any 1 kg/m2 increase in body mass index confers more risk (hazard ratio 1.03). Obesity might increase the likelihood of recurrence or mortality of the primary cancer and may affect initial management, including accurate staging. The risk maybe confounded by different factors, including lower adherence to organised CRC screening programmes. It is unclear whether bariatric surgery helps reduce rectal cancer risk. CONCLUSIONS: Despite a growing body of evidence linking obesity to CRC, many questions remain unanswered, including whether we should screen patients with obesity earlier or propose prophylactic bariatric surgery for certain patients with obesity.

Exome sequencing allows detection of relevant pharmacogenetic variants in epileptic patients.

Beyond the identification of causal genetic variants in the diagnosis of Mendelian disorders, exome sequencing can detect numerous variants with potential relevance for clinical care. Clinical interventions can thus be conducted to improve future health outcomes for patients and their at-risk relatives, such as predicting late-onset genetic disorders accessible to prevention, treatment or identifying differential drug efficacy and safety. To evaluate the interest of such pharmacogenetic information, we designed an "in house" pipeline to determine the status of 122 PharmGKB (Pharmacogenomics Knowledgebase) variant-drug combinations in 31 genes. This pipeline was applied to a cohort of 90 epileptic patients who had previously an exome sequencing (ES) analysis, to determine the frequency of pharmacogenetic variants. We performed a retrospective analysis of drug plasma concentrations and treatment efficacy in patients bearing at least one relevant PharmGKB variant. For PharmGKB level 1A variants, CYP2C9 status for phenytoin prescription was the only relevant information. Nineteen patients were treated with phenytoin, among phenytoin-treated patients, none were poor metabolizers and four were intermediate metabolizers. While being treated with a standard protocol (10-23 mg/kg/30 min loading dose followed by 5 mg/kg/8 h maintenance dose), all identified intermediate metabolizers had toxic plasma concentrations (20 mg/L). In epileptic patients, pangenomic sequencing can provide information about common pharmacogenetic variants likely to be useful to guide therapeutic drug monitoring, and in the case of phenytoin, to prevent clinical toxicity caused by high plasma levels.

Leptin-Induced HLA-G Inhibits Myometrial Contraction and Differentiation.

Maternal obesity is associated with a wide spectrum of labour disorders, including preterm birth. Leptin, a pro-inflammatory adipokine and a key factor of obesity, is suspected to play a major role in these disorders. OB-R, its receptor, is expressed on macrophages and myocytes, two cell types critical for labour onset. Macrophages secrete reactive oxygen species/pro-inflammatory cytokines, responsible for myometrial differentiation while myocytes control uterine contractions. In this study, we assessed the effect of leptin on myometrial contraction and differentiation using our validated co-culture model of human primary macrophages and myocytes. We demonstrated that leptin had a different effect on myocytes and macrophages depending on the dose. A low leptin concentration induced a tocolytic effect by preventing myocytes' contraction, differentiation, and macrophage-induced ROS production. Additionally, leptin led to an increase in HLA-G expression, suggesting that the tocolytic effect of leptin may be driven by HLA-G, a tolerogenic molecule. Finally, we observed that recombinant HLA-G also prevented LPS-induced ROS production by macrophages. Altogether, these data provide a putative molecular mechanism by which leptin may induce immune tolerance and therefore interfere with labour-associated mechanisms. Therefore, HLA-G represents a potential innovative therapeutic target in the pharmacological management of preterm labour.

Assessing the Acceptability of Home-Based HPV Self-Sampling: A Qualitative Study on Cervical Cancer Screening Conducted in Reunion Island Prior to the RESISTE Trial.

Cervical cancer incidence and mortality rates are 2 to 3 times higher in the overseas department of Reunion compared with mainland France. RESISTE's cluster-randomized controlled trial aims to test the effectiveness of home-based self-sampling (HBSS) through a high-risk oncogenic papillomavirus test sent out by post to women who have not been screened in the past 3 years, despite having been invited to do so through a reminder letter. Prior to the trial, qualitative research was carried out to understand screening barriers and assess anticipated acceptability. Semi-structured interviews were conducted with 35 women and 20 healthcare providers. Providers consider HBSS a viable method in reaching women who tend not to visit a doctor regularly, or who are reluctant to undergo a smear pap, as well as those who are geographically isolated. They considered, however, that women would require support, and that outreach was necessary to ensure more socially isolated women participate. The majority of the women surveyed were in favour of HBSS. However, two-thirds voiced concerns regarding the test's efficiency and their ability to perform the test correctly, without harming themselves. Based on these findings, recommendations were formulated to reassure women on usage and quality, and to help reach socially isolated women.

Violence against women and perceived health: An observational survey of patients treated in the multidisciplinary structure 'The Women's House' and two Family Planning Centres in the metropolitan Paris area.

It is unknown how many women seeking care at French Family Planning Centres (FPCs) endure, or have endured intimate partner violence (IPV). To assess the prevalence of IPV, we surveyed women seeking care at three FPCs in the metropolitan Paris area (Seine-Saint-Denis). We examined the associations between IPV, socio-demographic characteristics and perceptions of health according to six indicators. Of the FPCs included in our survey, two are standalone facilities and one is located in The Women's Home, a multidisciplinary structure dedicated to serving survivors of violence. We conducted an observational survey from December 2018 to February 2019. All women aged 18 years and older were eligible. We solicited data on socio-demographic factors, general stability and history of violence. We measured health status on a 10-point scale for six different symptoms. Of the 274 women who participated, 27% had experienced IPV. Women who reported experiencing, or having experienced IPV were more likely to be between 25 and 44 years old (than under 25), temporarily documented or undocumented, unemployed or seeking employment, and experiencing housing insecurity. Women seeking care at The Women's House were more than twice as likely to report IPV (42%) than those visiting FPC-2 or FPC-3 (20% and 16%, respectively). Reports of violence increase among women with uncertain legal status, housing, employment and lower self-rated health. Results suggest that a FPC located in a structure specifically dedicated to serving women victims-survivors of violence like the Women's House may be more attractive to survivors.

First use of Simulation in Therapeutic Patient Education (S-TPE) in adults with diabetes: a pilot study.

OBJECTIVE: To pilot test the feasibility and acceptability of Simulation in Therapeutic Patient Education (S-TPE), in both adult patients with diabetes and educators. CONCEPTION: Adult patients with insulin-dependent diabetes and who participated in a full TPE programme for the implementation of a FreeStyle were included in this monocentric pilot study. S-TPE intervention was based on a consensus conference determining the conditions and objectives of S-TPE. Main outcomes were the patients' and educators' perception of the usefulness of S-TPE and the patient's satisfaction level at the conclusion of the simulation sequence, measured on validated scales. Secondary outcomes were organisational, human, material and temporal, facilitating and limiting factors for patients and educators, patient self-efficacy and anxiety scores. INTERVENTIONS: The final session of TPE used the simulation. For each group, one patient volunteered to be the simulated patient. Intervention was divided into three steps: (1) a pre-briefing, (2) a simulation of hypoglycaemia and (3) a debriefing with the group of patients and educators. The whole intervention lasted about 2 hours. RESULTS: We included 23 patients (mean age ±SD 63±15 years, 14 men) and 3 educators. After S-TPE intervention, patients' and educators' perceived usefulness score were 20.6/25 and 37.5/40, respectively. Patient's satisfaction score was 51.9/60. Qualitative analysis revealed no limiting factors to implementing S-TPE. Self-efficacy was stable. Decrease in anxiety score after S-TPE reached statistical significance in women (from 35.1±4.5 to 32.7±5.5, p=0.04) but not in men. CONCLUSION: No limiting factors that could prevent the conduct of clinical trials to assess S-TPE efficacy in patients with diabetes were identified. S-TPE appears as a promising technique to improve diabetes management. TRIAL REGISTRATION NUMBER: Registration N°: 2019-A00773-54 and NTC: 03956927.

Health crisis: What opportunities for clinical drug research?

The COVID-19 pandemic led to the deployment of an unprecedented academic and industrial research effort, the sometimes redundant nature of which is regrettable, as is the lack of both national and international management. However, it must be noted that during this crisis, regulatory procedures were adapted and certain obstacles in the organisation of clinical research were partly removed to contribute to the deployment of trials as close as possible to patients and to facilitate monitoring and control procedures. The digitisation of certain processes and the decentralisation of certain activities were implemented under the cover of a mobilisation of the authorities and all institutional, academic and industrial players. While in the UK, the optimisation of resources through a single platform trial has made it possible to demonstrate or invalidate the efficacy of many treatments, in France the health crisis has highlighted the fragility of the organisation of clinical research, in particular a lack of coordination and funding, difficulties in implementing studies and a certain reluctance to share data. However, the crisis has also revealed the adaptability of the various stakeholders and has led to the improvement of several processes useful for the deployment of therapeutic innovation. Let us hope that the lessons learned during this crisis will allow for greater efficiency in the event of a new pandemic and, above all, that the progress made will continue to apply to all future clinical research activities.

Small Molecule Drugs in Inflammatory Bowel Diseases.

Inflammatory bowel diseases (IBDs), mainly represented by Crohn's disease (CD) and Ulcerative Colitis (UC), are chronic disorders with an unclear pathogenesis. This incurable and iterative intestinal mucosal inflammation requires the life-long use of anti-inflammatory drugs to prevent flares or relapses, which are the major providers of complications, such as small bowel strictures and intestinal perforations. The introduction of tumor necrosis factor (TNF)-alpha inhibitors and other compounds, such as anti-IL12/23 and anti-alpha4/beta7 integrin monoclonal antibodies, has considerably improved the clinical management of IBDs. They are now the standard of care, being the first-line therapy in patients with aggressive disease and in patients with moderate to severe disease with an inadequate response to conventional therapy. However, for approximately one third of all patients, their efficacy remains insufficient by a lack or loss of response due to the formation of anti-drug antibodies or compliance difficulties with parenteral formulations. To address these issues, orally administered Small Molecules Drugs (SMDs) that use a broad range of novel pharmacological pathways, such as JAK inhibitors, sphingosine-1-phosphate receptor modulators, and phosphodiesterase 4 inhibitors, have been developed for CD and UC. This article provides an updated and complete review of the most recently authorized SMDs and SMDs in phase II/III development.