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

Table 1 Case series summary

Case	Age	Sex	Disease	Classification	Failed/prior treatments	Final combined therapy	Response	Complications/key notes
1	57	M	UC	E3; Mayo 2 (residual Mayo 2, August, 2021)	Mesalazine; budesonide; azathioprine; infliximab escalated to monthly (partial) → add-on iJAK	IFX (IV 500 mg every 4 weeks during severe phase) + TOFA 5 mg twice a day (later simplified to SC IFX 240 mg every 2 weeks)	Yes (deep remission)	Partial response to IFX → add-on TOFA; no surgery
2	42	F	UC	E3 (prior E1 → E3); E2M3 (October, 2022) → E3M2 (December, 2023) → E3M0 (October, 2025)	Mesalazine (multiple incomplete); vedolizumab (secondary loss of response); IFX + AZA (AZA stopped cytopenia/anemia; IFX immunogenic failure ADA+); golimumab + TOFA (partial despite TOFA 10 twice a day + golimumab 100 monthly)	USK + TOFA (TOFA 10 mg three times daily for 30 days, then 10 mg twice a day → 5 mg twice a day; USK escalated to every 4 weeks)	Yes (deep remission)	Transaminase changes → TOFA de-escalation; colectomy avoided
3	28	M	CD	Montreal A2 L2B2p (colonic + perianal; inflammatory stricture)	Mesalazine; multiple antibiotics; upadacitinib 45 → 30 mg (partial: Perianal + symptoms improved but SES-CD 8, stenosis)	UPA + ADA (UPA 15 mg daily + ADA every 14 days)	Yes (deep response; SES-CD 1)	Perianal disease requiring procedures; hepatic flexure inflammatory stenosis
4	28	F	CD	Colonic Crohn’s	Mesalazine; azathioprine; IFX 5 mg/kg every 8 weeks → escalated every 4 weeks (no response; FC 3171; CRP/ESR high); ustekinumab IV induction; pregnancy required TOFA stop; later guselkumab	USK + TOFA (10 mg twice a day) (later stopped for pregnancy; later TOFA reintroduced with guselkumab)	Yes (initial deep response); later fluctuating	Pregnancy; relapse in 2nd trimester → USK every 4 weeks; postpartum relapse and switching
5	42	F	CD	Montreal A2 L3B2, stenosing; SES-CD 12	Prior IL-17 (ixekizumab) for PsA; prior ADA for arthritis ineffective; UPA 45 mg → 30 mg (partial clinical; FC 678; persistent SES-CD 12)	UPA + ADA (ADA induction + UPA 15 mg)	Partial/ongoing (awaiting reassessment)	Stenosing disease; sub-occlusive episodes; arthritis control drove UPA continuation
6	21	M	UC	E3M3	Azathioprine; mesalazine; steroid-dependent; golimumab + TOFA (failed); infliximab (failed); UPA induction (partial)	UPA + VDZ (UPA 30 mg + VDZ 300 mg every 8 weeks)	Yes (clinical + biochemical response)	Severe stool frequency early; steroid dependence; colectomy avoided
7	54	F	UC	E3M3 (rectosigmoid severe December, 2024)	Mesalazine high-dose; long-term VDZ; steroids; TOFA initial signal but non-durable; USK + TOFA failed; IFX rescue induction (3 doses) failed	USK + TOFA (failed) → IFX rescue (failed)	No (colectomy)	Colectomy + IPAA (March, 2025), reversal August, 2025; late pouchitis/cuffitis December, 2025
8	36	F	CD	Colonic Crohn’s; severe SES-CD 25 → 32	IFX (dose increase, no benefit); ADA; AZA; USK; UPA trial (no response); risankizumab partial; add-on TOFA; access constraints	Guselkumab + TOFA	Yes (clinical); colonoscopy pending	Multi-refractory; awaiting endoscopic confirmation
9	30	F	UC	E3 (E3M3 April, 2023; E3M2 July, 2024; Mayo 2 May, 2025)	IFX 2020-21 (stopped 2022 after pneumonia); AZA + mesalazine + steroids; VDZ partial; TOFA 5 mg → 10 mg twice a day + VDZ every 4 weeks partial; relapse when TOFA stopped	UPA + VDZ (UPA 30 mg maintenance; VDZ 300 mg every 8 weeks)	Yes (clinical); objective reassessment planned	Pneumonia led to IFX stop; repeated relapse on TOFA interruption; now stable on UPA + VDZ

UC: Ulcerative colitis; CD: Crohn’s disease; IFX: Infliximab; iJAK: Janus kinase inhibitor; TOFA: Tofacitinib; SC: Subcutaneous; AZA: Azathioprine; ADA: Adalimumab; USK: Ustekinumab; SES-CD: Simple Endoscopic Score for Crohn’s disease; IL: Interleukin; UPA: Upadacitinib; PsA: Psoriatic arthritis; FC: Fecal calprotectin; VDZ: Vedolizumab; IPAA: Ileal pouch-anal anastomosis.