Daily Brief

Introduction:

Despite an expanding range of advanced therapies for inflammatory bowel disease (IBD), many patients fail to achieve durable remission or lose response over time. TL1A is an attractive therapeutic target because it is implicated in both intestinal inflammation and fibrotic remodelling. The phase 2b RELIEVE UCCD trial evaluated duvakitug, an anti-TL1A monoclonal antibody, simultaneously in Crohn’s disease (CD) and ulcerative colitis (UC).

Why was this study needed?

Current therapies do not provide sustained disease control for many patients with moderate-to-severe IBD.

Persistent inflammation in CD can lead to progressive bowel damage and fibrosis.

TL1A inhibition potentially targets pathways involved in both inflammation and fibrosis.

The study importantly included both advanced therapy–naive and previously treated patients.

Results:

In Crohn’s disease, endoscopic response at week 14 occurred in 48% with duvakitug 900 mg vs 13% with placebo; response with 450 mg was 26%.

In ulcerative colitis, clinical remission occurred in 48% with 900 mg and 36% with 450 mg vs 20% with placebo.

Benefit was observed in both advanced therapy–experienced and therapy-naive patients, with a particularly encouraging signal for the 900-mg dose.

No new major safety signal emerged; common adverse events included anemia, nasopharyngitis, headache, and upper respiratory infections.

Clinical Impact:

The most interesting feature of TL1A inhibition is its potential to move beyond conventional inflammatory suppression toward disease modification, particularly if an effect on fibrosis can eventually be demonstrated. The strong endoscopic response in CD is therefore especially relevant.

However, this remains a relatively small 14-week phase 2b study. Whether these responses translate into durable endoscopic remission, reduced bowel damage, fewer strictures or surgery, and acceptable long-term safety requires phase 3 confirmation.

Bottom Line:

Duvakitug produced strong early efficacy in both Crohn’s disease and ulcerative colitis, including patients previously exposed to advanced therapies. Anti-TL1A therapy is emerging as one of the most promising new mechanistic classes in IBD—but durability, long-term safety, and true antifibrotic benefit remain the key questions for phase 3 trials.

Introduction:

Paclitaxel remains an important second-line treatment for advanced gastric cancer, but intravenous administration requires infusion-centre visits and carries risks of neuropathy and hypersensitivity reactions. This phase III trial evaluated whether an oral paclitaxel formulation could provide comparable—or superior—outcomes after progression on fluoropyrimidine-based therapy.

Why was this study needed?

IV paclitaxel creates substantial treatment and infusion burden.

An effective oral taxane could improve convenience and avoid routine hypersensitivity premedication.

Oral administration may produce a different toxicity profile from conventional IV paclitaxel.

Phase III evidence was required to establish efficacy.

Results:

Among 536 patients, oral paclitaxel significantly improved median overall survival: 9.13 vs 6.54 months (HR 0.77).

PFS was similar (3.02 vs 2.89 months) and met the predefined noninferiority criterion.

Objective response was numerically higher with oral therapy (13.6% vs 9.8%).

Oral paclitaxel caused less neuropathy, alopecia, and hypersensitivity, but more diarrhea and treatment interruptions.

Clinical Impact:

An oral taxane producing an overall-survival advantage while eliminating IV administration is clinically attractive. However, an important limitation is the comparator: q3-weekly IV paclitaxel does not represent the contemporary ramucirumab plus weekly paclitaxel standard used in many regions. In addition, the trial population was entirely Chinese, limiting immediate global generalizability.

Bottom Line:

Oral paclitaxel improved overall survival and reduced several classic taxane toxicities compared with q3-weekly IV paclitaxel in second-line advanced gastric cancer. It is a promising and convenient therapeutic option—but comparison with contemporary standards and broader international validation are needed before it becomes globally practice-changing.

Introduction:

Conventional ERCP relies on fluoroscopy for biliary imaging and stone extraction, exposing patients and endoscopy teams to ionising radiation. Fluoroscopy-free direct solitary cholangioscopy (DSC) offers direct intraductal visualisation and potentially eliminates radiation altogether. This randomised trial compared DSC with conventional ERCP for noncomplex bile-duct stones.

Why was this study needed?

ERCP exposes both patients and staff to cumulative radiation.

Direct cholangioscopy enables real-time visualisation of stones and bile ducts.

Whether a completely fluoroscopy-free approach can achieve comparable stone clearance required randomised evidence.

Such an approach could be particularly useful when radiation exposure should be minimized.

Results:

Among 250 randomized patients, stone clearance was 87.1% with DSC vs 88.9% with conventional ERCP, meeting the prespecified criterion for noninferiority.

DSC completely eliminated fluoroscopic radiation exposure: 0 vs 2106 Gy·cm² median dose-area product.

Serious adverse events were comparable (5.6% vs 4.0%).

The trade-off was procedure duration: DSC required approximately 10 minutes longer than conventional ERCP.

Clinical Impact:

This trial demonstrates that fluoroscopy is not necessarily indispensable for selected noncomplex bile-duct stone extraction. Fluoroscopy-free DSC could be particularly attractive when radiation avoidance is important or fluoroscopy access is limited.

However, the longer procedure time, equipment requirements, operator expertise, and applicability primarily to noncomplex stones currently favor selective rather than universal adoption.

Bottom Line:

Fluoroscopy-free direct cholangioscopy achieved bile-duct stone clearance comparable with conventional ERCP while completely eliminating radiation exposure, without increasing serious adverse events. The price is a longer procedure—but for selected patients, “ERCP without radiation” may now be a realistic option.

Introduction:

Gastric variceal bleeding (GVB) is a high-risk portal hypertensive emergency in which conventional endoscopic therapy may be inadequate. EUS-guided coil embolisation plus cyanoacrylate (EUS-Coils+CYA) offers targeted variceal obliteration, whereas TIPS plus variceal embolisation (TIPS+VE) reduces portal pressure while directly treating the varix. This multicenter study compared these two approaches.

Why was this study needed?

Both EUS-guided therapy and TIPS are increasingly used for GVB.

Direct comparative evidence remains limited.

Treatment selection must balance bleeding control against complications such as hepatic encephalopathy (HE) and embolisation.

Identifying patients better suited to each strategy could personalise GVB management.

Results:

After propensity matching, 124 patients were analyzed; technical success was 100% with both strategies.

Rebleeding was similar with EUS-Coils+CYA and TIPS+VE (11.3% vs 9.7%), with no significant mortality difference.

HE was substantially lower with EUS-Coils+CYA (1.6% vs 14.5%), while TIPS+VE also caused more postprocedural abdominal pain.

Conversely, EUS-Coils+CYA carried a 9.7% risk of ectopic embolization, all pulmonary embolic events, versus none with TIPS+VE.

Clinical Impact:

The study suggests there may be no universally superior intervention for gastric variceal bleeding. EUS-guided therapy provides comparable bleeding control without creating a portosystemic shunt and may therefore be attractive when HE is a major concern. TIPS remains particularly relevant when portal decompression itself is required, but its encephalopathy burden must be considered.

Importantly, the pulmonary embolization signal with EUS-Coils+CYA emphasizes the need for meticulous technique and careful control of cyanoacrylate delivery.

Bottom Line:

EUS-guided coil plus cyanoacrylate and TIPS plus variceal embolization achieved similar rebleeding and survival outcomes in gastric variceal bleeding—but with different complication profiles: EUS therapy produced far less hepatic encephalopathy, whereas TIPS avoided the ectopic embolization seen with cyanoacrylate. Treatment should therefore be individualized according to portal-hypertension physiology, HE risk, anatomy, and local expertise.