Beyond class switching in multi-refractory inflammatory bowel disease: Nine case reports and review of literature.

BACKGROUND: A clinically relevant subset of patients with inflammatory bowel disease (IBD) remain partial responders despite multiple advanced therapies. In this setting, reflexive class switching risks forfeiting incremental mechanistic gains, whereas a deliberate "build-on-partial-response" strategy - through dose optimization, extended induction, and, in selected cases, advanced combination therapy (ACT) [an oral Janus kinase inhibitor (iJAK) plus a biologic] - may consolidate disease control. However, real-world data supporting ACT remain limited, particularly regarding phenotype-driven selection, objective reassessment, and safety considerations. CASE SUMMARY: We report nine multi-refractory IBD patients [ulcerative colitis (UC), n = 5; Crohn's disease, n = 4] managed with ACT after incomplete response to an initial advanced therapy. UC strategies included infliximab plus tofacitinib, ustekinumab plus tofacitinib, and vedolizumab combined with iJAK. Crohn's disease cases illustrate three patterns: Add-on anti-tumor necrosis factor therapy after partial iJAK response (e.g., upadacitinib plus adalimumab in two patients with stenosing or perianal phenotypes), interleukin-23 pathway intensification combined with iJAK (guselkumab plus tofacitinib), and phenotype discordance between extraintestinal and luminal disease control. Overall, 8/9 patients (89%) achieved clinical response with improvement in biochemical markers and/or endoscopic findings; among these, 6/9 (67%) achieved documented deep remission (clinical and biochemical, with endoscopic confirmation in 5/6). One patient with severe refractory UC failed ustekinumab plus tofacitinib and infliximab rescue and proceeded to colectomy with ileal pouch construction (11%). Patients did not present any adverse event associated with therapy, only secondary to uncontrolled disease. CONCLUSION: In multi-refractory IBD, add-on ACT may convert partial response into deep remission, averting surgery in selected patients.