Introduction

Persistent High-Risk Human Papillomavirus (HR-HPV) infection can lead to an anal high-grade squamous intraepithelial lesion (HSIL), the precursor lesion to anal squamous cell carcinoma (SCC). Anal cytology and HR-HPV testing are strategies used for anal SCC screening. Anal HR-HPV prevalence in HIV-negative MSM and in MSM living with HIV (MSM-HIV) is 41% and 74%, respectively. The use of Pre-Exposure Prophylaxis (PrEP) in HIV-negative MSM to prevent HIV contraction created a new Sexual Minority Group among MSM, i.e. MSM using PrEP (MSM-PrEP). The aim of this study was to determine the prevalence of anal HR-HPV infection and abnormal anal cytology in MSM-PrEP and MSM-HIV.

Aims & Methods

MSM-PrEP and MSM-HIV were enrolled in this mono-centric study during consultations at the S-clinic and the HIV-reference centre respectively. Patient characteristics, sexual behavior and demographics were collected using a questionnaire, completed on the day of the anal swab testing.

Results

We enrolled 150 MSM-PrEP and 152 MSM-HIV. Quality of anal swabs was sufficient in respectively 96.7% (n=145) and 96.1% (n=146). HR-HPV prevalence in MSM-PrEP was comparable with HR-HPV prevalence in MSM-HIV; respectively 74.5% (n=108) and 76.6% (n=111) tested positive for at least one HR-HPV (p=0.78). No significant difference in abnormal cytology was seen; 53.1% (n=77) of the MSM-PrEP and 57.2%(n=83) of MSM-HIV had either ASCUS, ASC-H, LSIL or HSIL (p=0.56).

Conclusion

The risk of HR-HPV infection and abnormal anal cytology in MSM-PrEP is comparable to that in MSM-HIV, both of which are higher than observed in HIV-negative MSM not using PrEP. This heightened prevalence of HPV in MSM-PrEP poses an increased risk for HSIL. Recent guidelines on anal screening from International Anal Neoplasia Society recommend screening for anal cancer in both MSM-HIV and HIV-negative MSM, reflecting respective anal cancer incidence rates of 70-100 per 100,000 person-years and 18-34 per 100,000 person-years. Our findings suggest that MSM-PrEP constitutes a distinct risk group for anal SCC positioned between MSM-HIV and HIV-negative MSM not using PrEP.

References

Gaisa M, Gypsyamber D et al. Epidemiology of anal human papillomavirus infection and high-grade squamous intraepithelial lesions in 29 900 men according to HIV status, sexuality, and age: a collaborative pooled analysis of 64 studies. Lancet HIV. 2021;8(9):531-43.
Machalek D, Poynten M, Jin F et al. Anal human papillomavirus infection and associated neoplastic lesions in men who have sex with men: a systematic review and meta-analysis. Lancet Oncol. 2012;13(5):487-500.
Stier E, Clarke M, Deshmukh A et al. International Anal Neoplasia Society's consensus guidelines for anal cancer screening.Int.J.Cancer.2024;154:1694-1702.

Introduction

Despite the progress in advanced therapies (AT) for ulcerative colitis (UC), selecting a second-line treatment after failure remains challenging. Recent guidelines recommend Ustekinumab (UST), Tofacitinib (TOFA), or Upadacitinib (UPA) as high-efficacy options after prior AT failure. However, no real-world studies have compared all three therapies.

Aims & Methods

Retrospective multicenter study (8 centers) of UC patients who failed ≥1 advanced therapy. Patients were stratified into UST, TOFA, or UPA groups and assessed at 16 and 52 weeks. The primary outcome was steroid-free clinical remission (SFCR) based on the Patient Reported Outcomes-2. Secondary outcomes included biochemical remission (fecal calprotectin ≤ 250 µg/g) and endoscopic remission (Mayo Endoscopic Subscore=0). Time to remission was assessed using Cox regression analysis. A subanalysis was performed including only second-line use after anti-TNF failure. Multivariate analysis was performed, adjusted for duration of disease, extent and number of prior therapies.

Results

We evaluated 259 cases [54.4% (n=141) female; diagnostic age 32.3 ± 15.1 years] who initiated UST (n=105; 40.5%), UPA (n=87; 33.6%) or TOFA (n=67; 25.9%). The groups were similar in disease duration (UST: 11.6 ± 8.0; UPA: 9.8 ± 6.4; TOFA: 10.4 ± 5.4 years) and 49.8% (n=129) had failed ≥2 previous AT
At week 16, UPA showed higher SFCR compared to UST (OR 2.1; p=0.014) and TOFA (OR 2.1; p=0.040), with no difference at week 52. Biochemical remission was higher with UPA at week 16 vs UST (OR 2.3; p=0.015) and TOFA (OR 2.1; p=0.039) and at week 52 vs UST (OR 4.7; p=0.010) and TOFA (OR 4.6; p=0.013). At week 16, endoscopic remission was higher with UST (OR 3.5; p=0.036) and UPA (OR 3.1; p=0.041) compared to TOFA; and at week 52, UPA was associated with higher endoscopic remission vs UST (OR 3.6; p=0.036).
In Cox regression, UPA achieved earlier biochemical remission than UST (HR 1.9; p<0.001) and TOFA (HR 1.8; p=0.011). JAK inhibitors led to earlier endoscopic remission than UST (vs UPA: HR 3.2; p<0.001; vs TOFA: HR 1.4; p=0.002).
In the subanalysis, UPA as second-line therapy demonstrated higher SFCR than TOFA (OR 3.6; p=0.035) and higher endoscopic remission at week 52 than TOFA (OR 12.0; p=0.017), and trend-wise compared to UST (OR 4.5; p=0.090).

Conclusion

Even though all three medication demonstrated high efficacy in bio-exposed UC patients, UPA achieved better results in this real world study.

References

Singh, Siddharth, et al. "AGA living clinical practice guideline on pharmacological management of moderate-to-severe ulcerative colitis." Gastroenterology 167.7 (2024): 1307-1343.

Clinical Case Summary

Introduction: Locally advanced pancreatic tumors can lead to both biliary and duodenal obstruction by invasion or compression. Quality of life is severely affected if obstruction occurs: jaundice, emesis and pain can become invalidating and patients become too frail for palliative chemotherapy and are sometimes declared unfit even for derivative surgery. Recently, endoscopic techniques under EUS or ERCP guidance are being used to create biliodigestive and enteral anastomoses.
Clinical case: A 75-year-old female was diagnosed with locally advanced pancreatic head adenocarcinoma in January 2024. The tumor was declared unresectable and chemotherapy was initiated. A plastic stent was inserted into the main biliary duct (MBD) to ensure biliary drainage. In May 2024, she presented with cholangitis and emesis. EGD revealed duodenal stenosis and ERCP failed due to tumor infiltration. A combined endoscopic approach was performed: EUS-guided hepatico-gastrostomy (EHG) for biliary drainage and EUS-guided gastro-enterostomy using a lumen-apposing metal stent (LAMS). In July 2024, the plastic stent was removed, and in August 2024, two fully covered 60 x 10 mm SEMS were inserted antegrade through the EHG into the MBD to improve patency. At 11 months post-intervention, the patient returned for routine reassessment, declaring good clinical performance: she remained asymptomatic, with routine blood tests, including bilirubin levels within normal range and with all stents patent and correctly positioned (confirmed radiologically and endoscopically). The patient was able to maintain oral intake and continue chemotherapy. No late adverse events were noted.
Conclusion: This case demonstrates the long-term clinical and technical success of a staged endoscopic triple bypass for the management of complex biliary and duodenal obstruction due to unresectable pancreatic cancer. The approach was minimally invasive, well tolerated and remarkably improved the patient's quality of life.

References

1. Adler, Douglas G MD; Baron, Todd H MD, FACP. Endoscopic Palliation of Malignant Gastric Outlet Obstruction Using Self-Expanding Metal Stents: Experience in 36 Patients. American Journal of Gastroenterology 97(1):p 72-78, January 2002. | DOI: 10.1111/j.1572-0241.2002.05423.x
2. Giovannini, Marc. (2019). EUS-guided hepaticogastrostomy. Endoscopic Ultrasound. 8. 35. 10.4103/eus.eus_47_19.
3. Dumonceau, Jean-Marc & Tringali, Andrea & Blero, Daniel & Devière, J & Laugiers, R & Heresbach, D & Costamagna, Guido. (2012). Biliary stenting: Indications, choice of stents and results: European Society of Gastrointestinal Endoscopy (ESGE) clinical guideline. Endoscopy. 44. 277-98. 10.1055/s-0031-1291633.
4. Van Der Merwe, S. W., Van Wanrooij, R. L., Bronswijk, M., Everett, S., Lakhtakia, S., Rimbas, M., ... & Van Hooft, J. E. (2022). Therapeutic endoscopic ultrasound: European society of gastrointestinal endoscopy (ESGE) guideline. Endoscopy, 54(02), 185-205. 10.1055/a-1717-1391

Introduction

In Australian patients receiving intravenous (IV) infliximab (IFX) treatment, 44% of patients do not respond to standard regimen and require dose escalation within a year. The REMSWITCH (6-month evaluation) and REMSWITCH-LT (18-months evaluation) investigated the effectiveness of switching from IV to subcutaneous (SC) IFX in patients with inflammatory bowel disease (IBD) who received standard and dose-escalated IV regimen. The two studies concluded that a fixed dose of 120 mg Q2W is feasible, safe and well-accepted leading to a low risk of long-term relapse in patients with escalated IV doses except for those on 10mg/kg/4weeks regimen. In this study, we developed a model to estimate the financial implications of switching.

Aims & Methods

Clinical efficacy parameters were derived from the REMSWITCH and REMSWITCH-LT studies and applied to the Australian context. Number of Australian patients who are on IFX, the proportion of patients on dose escalated regimen, and cost parameters were identified from the published literature or publicly available resources. A financial model was developed based on the assumption that a cohort of patients will receive either IV or SC IFX, and the analysis concluded with the cost difference.

Results

The model assumes that a total of 5.6K patients are receiving IV IFX, with 44.2% of them receiving dose escalation and/or shortened interval of IV IFX. The model produced 6 months and 12 months results, suggesting savings between 582 and 882 AUD per patient, respectively, and equates to a yearly societal savings of 5 million AUD.

Conclusion

IFX SC deserves premium over IFX IV, given that the novel formulation offers tangible and intangible benefits that originator Remicade and biosimilars cannot provide. There is a concern regarding the affordability of SC IFX because it is generally priced higher than IV IFX, which has many biosimilars on the market. However, this study asserts that fixed dosing of 120mg of IFX is cost-saving for society, considering highly prevalent practice of dose escalation and/or shortened intervals of IFX regimen.