Dataset Information

Safety and Efficacy of Tofacitinib in Combination With Biologic Therapy for Refractory Crohn's Disease.

ABSTRACT:

Background

The majority of patients with Crohn's disease (CD) will not achieve endoscopic remission on current therapy. Addition of tofacitinib to biologics may improve remission rates.

Methods

We retrospectively assessed safety and clinical and endoscopic effectiveness of off-label tofacitinib and biologics for CD.

Results

We identified 19 patients treated with tofacitinib and a biologic for refractory CD between 2017 and 2019. Tofacitinib was added for luminal disease on colonoscopy (n = 13), luminal disease on capsule (n = 3), and pyoderma gangrenosum (n = 3). The mean age was 41.2 years (28-62), mean disease was duration 16.9 years (6-36), and prior exposure to biologics was a median of 4 (1-6). Mean treatment duration was 9.6 months (SD, 3.3). Adverse events (AEs) were reported in 36.8% of patients, most commonly minor infection or CD flare, and no patients had a serious AE; 80.0% (n = 8) achieved clinical response, and 60.0% (n = 6) achieved clinical remission based on Harvey-Bradshaw Index. Endoscopic improvement occurred in 54.5% (n = 6), endoscopic remission in 18.2% (n = 2), and endoscopic healing in 18.2% (n = 2) of patients. Mean Simple Endoscopic Score in CD significantly improved from 13.6 ± 5.2 to 6.5 ± 4.0 after treatment (P < .01).

Conclusions

In patients treated with tofacitinib in combination with a biologic, no new safety signals were observed. Combination tofacitinib and a biologic was effective in achieving clinical and endoscopic improvement in some patients with severe, refractory CD, although a larger sample size is needed to further assess the efficacy and long-term safety of this treatment strategy.

SUBMITTER: Lee SD

PROVIDER: S-EPMC8804506 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature

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Publications

Safety and Efficacy of Tofacitinib in Combination With Biologic Therapy for Refractory Crohn's Disease.

Lee Scott David SD Singla Anand A Harper Jason J Barahimi Mitra M Jacobs Jeffrey J Kamp Kendra J KJ Clark-Snustad Kindra Dawn KD

Inflammatory bowel diseases 20220201 2

<h4>Background</h4>The majority of patients with Crohn's disease (CD) will not achieve endoscopic remission on current therapy. Addition of tofacitinib to biologics may improve remission rates.<h4>Methods</h4>We retrospectively assessed safety and clinical and endoscopic effectiveness of off-label tofacitinib and biologics for CD.<h4>Results</h4>We identified 19 patients treated with tofacitinib and a biologic for refractory CD between 2017 and 2019. Tofacitinib was added for luminal disease on ...[more]

PMID: 34347103

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Project description:BackgroundBiologic therapies in patients with Crohn's disease often yield low clinical and endoscopic remission rates. After multiple failed therapies, combining two biologic therapies is possibly the sole medical alternative to recurrent surgery. However, data on this approach are limited.AimsTo assess the efficacy and safety of concomitant use of two biologic therapies in the largest cohort to date of refractory Crohn's disease patients.MethodsData were extracted from Crohn's disease patients started on dual biologic therapy at two referral centres. Biologics utilised include infliximab, adalimumab, vedolizumab, ustekinumab, certolizumab and golimumab. The primary outcome was endoscopic improvement (>50% reduction in Simplified Endoscopic Score-Crohn's disease [SES-CD] or explicitly stated). Endoscopic remission (SES-CD < 3 or stated), clinical response (Crohn's disease-patient-reported outcome-2 score [PRO2] reduced by 8), clinical remission (PRO2 < 8), and C-reactive protein (CRP) were also assessed.ResultsA total of 22 patients with 24 therapeutic trials of dual biologic therapy were identified. The majority of patients had prior surgical resections (91%), stricturing (59%) or penetrating (36%) phenotype, and perianal fistulas (50%). Median number of prior failed biologics was 4. Endoscopic improvement occurred in 43% of trials and 26% achieved endoscopic remission. Fifty per cent had clinical response and 41% achieved clinical remission. There were significant post-treatment reductions in median SES-CD (14.0 [12.0-17.5] to 6.0 [2.5-8.0], P = 0.0005], PRO-2 (24.1 [20.3-27.0] to 13.4 [4.6-21.8], P = 0.002] and CRP (17.0 [11.0-24.0] to 9.0 [4.0-14.0], P = 0.02). Presence of perianal fistulas decreased from 50% to 33%. Adverse events occurred in 13% of trials.ConclusionDual biologic therapy was associated with clinical, biomarker and endoscopic improvements in selected patients with refractory Crohn's disease who failed multiple biologics. Further studies are needed to validate this approach.

Project description:BACKGROUND:Recent studies have shown that oral combination antibiotics may improve disease course in refractory inflammatory bowel disease (IBD). Here, we describe the use of combination oral antibiotics as salvage therapy in refractory ulcerative colitis (UC), Crohn's colitis, and IBD-unclassified (IBD-U) at a large pediatric IBD center. METHODS:Clinical response, disease activity indices, adverse events, and clinical outcomes were measured up to 1 year after antibiotic treatment in this retrospective cohort study of children with medically refractory IBD colitis. RESULTS:Sixty-three patients with refractory UC, Crohn's colitis, and IBD-U (median age [interquartile range {IQR}], 15.3 [11.2-16.5] years; median disease duration [IQR], 1.2 [0.41-4.6] years) received a combination of 3 or 4 oral antibiotics (most commonly amoxicillin, metronidazole, and either doxycycline or ciprofloxacin) for a median (IQR) of 29 (21-58) days. Thirty-four patients (54%) were deemed corticosteroid-refractory or -dependent, with the majority (62/63) having a previous or present loss of response or primary nonresponse to anti-tumor necrosis factor alpha (anti-TNF?) therapy. Use of combination antibiotics led to a significant decrease in median Pediatric Ulcerative Colitis Activity Index (PUCAI) score (IQR) from 55 (40-65) to 10 (0-40; P < 0.0001) over 3 ± 1 weeks, with 25/63 (39.7%) patients achieving clinical remission (PUCAI <10 points). The clinical benefits of oral antibiotics were independent of anti-TNF? therapy optimization. Among children entering clinical remission (n = 25), only 1 patient required surgery at 1-year follow-up, vs 10 patients in the nonresponder group. Negative predictors of response to combination antibiotics were exposure to doxycycline (odds ratio [OR], 0.25; 95% CI, 0.08-0.76) and PUCAI ?65 at baseline (OR, 0.2; 95% CI, 0.05-0.74). CONCLUSIONS:Oral combination antibiotics appears to be an effective rescue and steroid-sparing therapy to induce remission in the short term in patients failing a biologic.

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Dataset Information

Safety and Efficacy of Tofacitinib in Combination With Biologic Therapy for Refractory Crohn's Disease.

Background

Methods

Results

Conclusions

Publications

Safety and Efficacy of Tofacitinib in Combination With Biologic Therapy for Refractory Crohn's Disease.

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