Retrospective Database Analysis: Dose Escalation and Adherence in Patients Initiating Biologics for Ulcerative Colitis

Background: Biologic therapies are often used in patients with ulcerative colitis who are non-responsive to conventional treatments. However, non-response or loss of response to biologics often occurs, leading to dose escalation, combination therapy, and/or treatment switching. We investigated real-world treatment patterns of biologic therapies among patients with ulcerative colitis in the USA. Methods: This study analyzed data from the IBM® MarketScan® Commercial and Medicare Supplemental Databases (medical/pharmacy claims for >250 million patients in the USA) to identify patients with ulcerative colitis initiating a biologic therapy (adalimumab, infliximab, golimumab, or vedolizumab) with 12 months of follow-up post-initiation. Key measures were patient baseline characteristics, dose escalation (average maintenance dose >20% higher than label), adherence (proportion of days covered), and ulcerative colitis-related healthcare costs in the 12 months following biologic therapy initiation. Results: Of 2,331 patients included in the study (adalimumab [N=1,291], infliximab [N=810], golimumab [N=127], vedolizumab [N=103]), 28.1% used concomitant immunosuppressant therapy within 12 months post-initiation. Overall, 23.6% (adalimumab), 34.8% (infliximab), 9.9% (golimumab), and 39.2% (vedolizumab) of patients dose escalated within 12 months. Patients who dose escalated incurred $20,106 higher total ulcerative colitis-related healthcare costs over 12 months than those who did not. Adherence (covariate-adjusted proportion of days covered) ranged from 0.63 to 0.73, and 39.3% of patients discontinued within 12 months (median treatment duration=112 days). Conclusion: Dose escalation was common, and incurred higher costs, in patients with ulcerative colitis initiating biologic therapies. Sub-optimal adherence and/or discontinuation within 12 months of initiation occurred frequently, highlighting the challenges in managing these patients.

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P562 5-ASA in ulcerative colitis: Are they really needed in the biological therapy era?

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjz203.690 ◽

2020 ◽

Vol 14 (Supplement_1) ◽

pp. S474-S474

Author(s):

C Arieira ◽

F Dias de Castro ◽

T Cúrdia Gonçalves ◽

M J Moreira ◽

J Cotter

Keyword(s):

Colorectal Cancer ◽

Ulcerative Colitis ◽

Biologic Therapy ◽

Fecal Calprotectin ◽

Inflammatory Biomarkers ◽

Faecal Calprotectin ◽

Reactive Protein ◽

Maintenance Of Remission ◽

Treatment Escalation

Abstract Background Biologic therapy has demonstrated efficacy for induction and maintenance of remission in ulcerative colitis (UC). However, it remains unclear whether oral aminosalicylates (5-ASA) should be continued or stopped after treatment escalation to biologics. The aim of the study was to evaluate differences in inflammatory biomarkers or the occurrence of complications in UC patients being treated with a combination of 5-ASA and biologics vs. biologics alone. Methods Retrospective study, including patients with UC and on biologic therapy with a minimum follow-up of 6 months. Collected inflammatory biomarkers were faecal calprotectin, C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR). The occurrence of complications was defined as the need of hospitalisation, need of corticosteroids or other top-up therapy, surgery and the occurrence of dysplasia or colorectal cancer. Results We included 65 patients with UC, 56.9% female with a mean age of 32.8 (±12.8) years. The median follow-up was 30 (6–132) months. Regarding extension, 61.5% were E3, 35.4% E2 and 3.1% E1. While 44 patients (67.7%) were on 5-ASA and biologics (infliximab = 32, adalimumab = 6, vedolizumab = 6), 21 (32.3%) were on biologics alone (infliximab = 13, adalimumab = 3, vedolizumab = 5). The median duration of biologic therapy was 30 (6–126) months. Regarding baseline characteristics, including age, gender, duration of the disease or biologic therapy and age at UC diagnosis, there were no differences between groups. No differences regarding inflammatory biomarkers were observed – fecal calprotectin (p = 0.39), CRP (p = 0.9) and ESR (p = 0.61). No differences were found regarding complications, namely the need of hospitalisation (p = 0.06) or need of corticosteroids (p = 0.89). Only one patient developed dysplasia (under infliximab and 5-ASA). Any of the included patients needed surgery or developed colorectal cancer. Conclusion About two-thirds of the UC patients under biologics are co-treated with 5-ASA. No differences between UC patients under combination biologics+5-ASA vs. biologics alone were found regarding inflammatory biomarkers or the occurrence of complications. These results raise the question if continuing 5-ASA in UC patients under biologics is really necessary.

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P663 Efficacy of tofacitinib in patients with ulcerative colitis after previous ineffective biological therapies

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjz203.791 ◽

2020 ◽

Vol 14 (Supplement_1) ◽

pp. S545-S546

Author(s):

M Rutka ◽

K Farkas ◽

D Pigniczki ◽

K Szántó ◽

B Anita ◽

...

Keyword(s):

Ulcerative Colitis ◽

Clinical Response ◽

Induction Therapy ◽

Dose Escalation ◽

Real Life ◽

Janus Kinase ◽

Inadequate Response ◽

Mayo Score ◽

Number Of Patients

Abstract Background Tofacitinib (TFC) is an oral, small-molecule Janus kinase inhibitor, which was recently approved for moderate to severe ulcerative colitis (UC). The aim of the current real-life study was to determine efficacy of TFC induction therapy regarding the clinical response and remission in patients with active UC. We evaluated short-term efficacy data in a Hungarian cohort with prior exposure to other biological agents such as anti-TNF drugs and vedolizumab. Methods In this single-centre retrospective study, patients with TFC introduction were included. Since January 2019, a total of 16 patients received an oral TFC induction therapy in a dose of 10 mg twice daily for 8 weeks. Endoscopic activity was evaluated by endoscopic Mayo (eMayo) score before the introduction of TFC and in case of an inadequate therapeutic response to the 5-mg-therapy to confirm therapeutic decision-making. Based on the evaluation of clinical symptoms and laboratory parameters, we either kept the dosage or reduced the dose to 5 mg according to local regulations. We also collected data from the 16. and 24. weeks of the therapy. Primary endpoints were a clinical response (as a reduction in partial Mayo Score [pMayo] by minimum 3 points) or remission (as a Mayo score of the maximum of 2 points and without blood in stool) at week 8. Results Sixteen patients had received the induction therapy (mean age: 36 years, 7 males and 9 females) in our centre. After 8 weeks, 12 (75%) patients responded to the TFC induction therapy and 6 (37.5%) of them were in remission. Four patients were primary non-responders (25%). Corticosteroid therapy (18 ± 7 mg) was required during the induction in 4 responder cases, which could be stepped down by week 8. As a continuous maintenance therapy, 4 patients have already reached the 16th week and 8 have completed the 24th week. By the end of the follow-up, 12 patients responded and 10 was in remission. During the observation period, 3 patients had to remain on 10 mg TFC dose, 6 patients required dose escalation from 5 mg to 10 mg and 5 mg was sufficient in case of only 3 patients after the introduction. Endoscopic activity showed a moderate decrease from 2.5 ± 0.5 eMayo score to 2 ± 1 (n = 7) until week 16. In respect the responder patients, CRP levels decreased from the mean of 7.23 to 5.02. No serious side-effects were observed during the follow-up. Conclusion After the 8-week TFC induction therapy, the response rate was high and only every fourth patients were non-responder. A low number of patients had adequate reactions to the 5 mg-therapy after the introduction, but TFC is effective with dose-escalation in respect of clinical response and remission in patients with UC, who have had an inadequate response to previous biological therapy.

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New Potential Weapons for Refractory Scleritis in the Era of Targeted Therapy

Mediators of Inflammation ◽

10.1155/2020/8294560 ◽

2020 ◽

Vol 2020 ◽

pp. 1-6 ◽

Cited By ~ 2

Author(s):

Claudia Fabiani ◽

Jurgen Sota ◽

Maite Sainz-de-la-Maza ◽

Laura Pelegrín ◽

Giacomo Emmi ◽

...

Keyword(s):

Tumor Necrosis ◽

Biologic Therapy ◽

Biologic Agents ◽

Biologic Therapies ◽

Biologic Drugs ◽

Corrected Visual Acuity ◽

Immune Mediated ◽

Number Of Patients ◽

Necrosis Factor

Objective. To assess the efficacy of biologic drugs, beyond tumor necrosis factor- (TNF-) α inhibitors, in the management of noninfectious refractory scleritis, either idiopathic or associated with systemic immune-mediated disorders. Patients and Methods. This is a retrospective study assessing the efficacy of several biologic agents (rituximab, anakinra, tocilizumab, and abatacept) and the small molecule tofacitinib in the treatment of scleritis through assessment of scleral inflammation and relapses, as well as treatment impact on best-corrected visual acuity (BCVA) and safety profile. Results. Fourteen patients (19 eyes) were enrolled in the study. Scleritis inflammatory grading significantly improved from baseline to 3 months (p=0.002) and from baseline to the last follow-up visit (p=0.002). Scleritis relapses significantly decreased between the 12 months preceding and following biologic therapy (p=0.007). No differences regarding BCVA were observed (p=0.67). Regarding adverse events, only one patient developed pneumonia and septic shock under rituximab treatment. Conclusions. Our results, though limited to a low number of patients, highlight the effectiveness of different biologic therapies in the treatment of noninfectious refractory scleritis, showing to control scleral inflammation and allowing a significant reduction in the number of relapses.

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Remission of Recalcitrant Psoriasis on Combined Biologic Therapy With Infliximab and Ustekinumab

Journal of Psoriasis and Psoriatic Arthritis ◽

10.1177/24755303211029598 ◽

2021 ◽

pp. 247553032110295

Author(s):

Kayla H. Taylor ◽

Steven R. Feldman

Keyword(s):

Ulcerative Colitis ◽

Adverse Effects ◽

Biologic Therapy ◽

Biologic Therapies ◽

Case Presentation ◽

Inflammatory Bowel ◽

Psoriatic Lesions ◽

Long Term Adverse Effects ◽

Systemic Therapies

Introduction: Anti-TNF treatment is effective for inflammatory bowel disease (IBD), however it also has the potential to cause paradoxical psoriasis which can be challenging to manage. Discontinuation of anti-TNF agents may improve psoriatic lesions but may worsen IBD. Combining biologic therapies, though not yet commonly practiced, may be a useful approach to the treatment of both conditions. Case Presentation: We describe a case of paradoxical palmoplantar psoriasis in a 48-year-old woman with ulcerative colitis (UC). Her UC was well-managed on infliximab. Following trials of several other topical and systemic therapies for her psoriatic lesions, she ultimately received relief on combined ustekinumab and infliximab therapy without flare of her IBD. Discussion: While other publications report success using ustekinumab for paradoxical psoriasis following cessation of infliximab, this case report highlights successful treatment using a combination of ustekinumab and infliximab with no reported adverse effects at 3 months. Conclusion: Discontinuation of the anti-TNF agent and use of a single biologic that may treat both IBD and psoriasis is a treatment option. Additionally, combining biologic therapies, though not yet commonly practiced, may be a useful, albeit costly, approach to prevent potential flares of IBD that may accompany cessation of some biologics. Further studies may be beneficial to assess for long term adverse effects.

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Granulocyte-Monocyte Apheresis in Steroid-Dependent, Azathioprine-Intolerant/Resistant Moderate Ulcerative Colitis: A Prospective Multicenter Study

Gastroenterology Research and Practice ◽

10.1155/2017/9728324 ◽

2017 ◽

Vol 2017 ◽

pp. 1-5

Author(s):

Gianni Imperiali ◽

Arnaldo Amato ◽

Maria Maddalena Terpin ◽

Ivo Beverina ◽

Aurora Bortoli ◽

...

Keyword(s):

Ulcerative Colitis ◽

Clinical Remission ◽

Biological Therapy ◽

Biologic Therapy ◽

Inclusion Criteria ◽

Prospective Multicenter Study ◽

Steroid Dependent ◽

Specific Subgroup ◽

One Year

Background. Granulocyte-monocyte apheresis has been proposed for the treatment of ulcerative colitis, although it is limited by costs and variability of results. Aim. To assess effectiveness of granulocyte-monocyte apheresis in patients with steroid-dependent, azathioprine-intolerant/resistant moderate ulcerative colitis. Methods. Consecutive patients fulfilling inclusion criteria were prospectively enrolled, treated by apheresis, and followed up for 12 months. The primary end point of the study was steroid-free clinical remission at 12 months, with no need for biologic therapy or surgery. Results. From January to December 2013, 33 patients were enrolled. After one year of follow-up, 12 (36%) patients had clinical remission, were steroid-free, and had no need for biological therapy or surgery; 3 (9%) cases showed a clinical response (but not clinical remission). Moreover, 12 (36%) patients required biologic therapy, 4 (12%) underwent colectomy, and in the other 2 (6%) a reduction, but not withdrawal, of steroid dose was achieved. Conclusions. Our study shows that a standard course of granulocyte-monocyte apheresis is associated with a 36% steroid-free clinical remission in patients with steroid-dependent, azathioprine-intolerant or resistant moderate ulcerative colitis. Apheresis might represent an alternative to biologic therapy or surgery in this specific subgroup of patients. This trial is registered with Clinicaltrial.gov NCT03189888.

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P423 Treatment escalation and associated cost in German Ulcerative Colitis patients treated with advanced therapies

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjab076.547 ◽

2021 ◽

Vol 15 (Supplement_1) ◽

pp. S427-S427

Author(s):

N Picker ◽

H Patel ◽

T Wilke ◽

L Rosin ◽

B Bokemeyer

Keyword(s):

Ulcerative Colitis ◽

Dose Escalation ◽

Drug Costs ◽

P Value ◽

First Year ◽

Prescription Data ◽

Kaplan Meier ◽

Advanced Therapy ◽

Advanced Therapies

Abstract Background Advanced therapies used in moderate-to-severe Ulcerative Colitis (UC) may show a secondary loss of response (LOR) over time, requiring patients to undergo dose escalation or switching. Our study aimed to investigate the frequency of dose escalation in real-world practice and evaluated the associated cost. Methods Using German claims data (AOK PLUS) including prescription data, we identified UC patients by either at least two confirmed outpatient diagnoses or one primary inpatient diagnosis (ICD-10 K51). Analyzed patients initiated an advanced therapy (anti-TNF, vedolizumab, tofacitinib) between 01/01/2015-30/06/2019. Therapy escalation was defined as dose increase exceeding the recommended maintenance dose according to product labels by more than 150%. Time to first escalation was analyzed using a Kaplan-Meier estimation. The observation ended with the discontinuation of index therapy + 90 days, or loss to follow-up, whatever occurred first. End of therapy was determined in case of a supply gap of >60 days or switch of the advanced therapy. Patients with a follow-up < 6 months were excluded.Direct UC-related resource use and costs accounting for hospitalizations, outpatient treatment, drug costs according to pharmacy sales prices were reported per patient-year (PY). Results Among 574 UC patients who initiated an advanced therapy, 328 patients (median age: 37 years; female: 52.1%; biologic-naïve: 85.4%) with sufficient follow-up time (median: 12.2 months) were identified. Out of these, 59 patients (19%) were dose-escalated within the first year, whereas 73 patients (22%; anti-TNF: 61; vedolizumab: 12) were found to experience a therapy escalation during the whole follow-up time (average daily dose during maintenance therapy: adalimumab: 5.3 mg, infliximab: 14.6 mg, golimumab: 3.7 mg, vedolizumab: 11.1 mg, tofacitinib: n/a). Total observed direct cost related to UC amounted to €39,514/PY (95%-CI: 37,469-41,558), with €37,369/PY (34,852-39,885; Figure 1) caused by UC-related medication (95%). In comparison, UC-related total direct costs and drug costs for patients without any observable escalation were much lower (€30,425/PY [29,672-31,178]; p-value <0.001 and €28,066/PY [27,230-28,902]; p-value <0.001). Frequency of hospitalizations due to UC (0.3 [0.2-0.5] vs. 0.4 [0.3-0.5]; p-value: 0.947) and gastroenterologist visits (2.1 [1.6-2.6] vs. 2.3 [2.1-2.5]; p-value: 0.361) were similar among both groups. Conclusion Nearly one-fifth of observed patients required therapy escalation in the first year, most likely due to secondary LOR. This results in higher UC-related costs. Payers should consider rates and costs of dose escalations when evaluating the cost-effectiveness of advanced therapies.

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P466 Acute Severe Ulcerative Colitis in the modern era: biologic therapy-exposed patients and salvage therapy with intensified infliximab

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjab076.589 ◽

2021 ◽

Vol 15 (Supplement_1) ◽

pp. S457-S457

Author(s):

K Fasoulas ◽

K Soufleris ◽

N Kafalis ◽

P Kevrekidou ◽

S Bouzoukas ◽

...

Keyword(s):

Ulcerative Colitis ◽

Medical Therapy ◽

Salvage Therapy ◽

Biologic Therapy ◽

Rescue Therapy ◽

Fecal Calprotectin ◽

Disease Extent ◽

Severe Ulcerative Colitis ◽

Modern Era

Abstract Background Acute Severe Ulcerative Colitis (ASUC) is still associated with significant morbidity and risk of colectomy, almost 70 years since the landmark study of Truelove-Witts established steroid efficacy and 15 years since the Järnerot study introduced infliximab as an effective rescue therapy. It remains unclear if management of ASUC in the modern era (biologic-exposed patients and intensified infliximab regimens) leads to different outcomes. Methods A retrospective review of all recently hospitalized ASUC patients was performed. We aimed to compare rates of colectomy, response to steroids, and response to salvage infliximab in bio-naive and bio-exposed patients. Intensified infliximab was used as salvage therapy: 10 mg/kg infusions, aiming a trough level of at least 10 μg/ml at Week 10. We also tried to identify disease and patient related characteristics predictive of colectomy or response to medical therapy. Results 50 patients were included (male 66%, mean age: 47.4 years) and followed up for a mean of 24.2 months. 24 patients (48%) experienced ASUC while on biologic therapy: 11 on infliximab, 6 on vedolizumab, 5 on adalimumab, 2 on golimumab. Endoscopy showed deep ulcers at 23 patients (47%). Fecal calprotectin was > 1800 ng/ml in all patients. Half the patients (25) received rescue therapy with Infliximab due to steroid refractoriness. Eleven patients (22%) underwent colectomy, 2 (4%) of which during the index hospitalization. Although colectomy rates were similar among bio-naïve and bio-exposed (20% vs 25%, p:0.675), bio-exposed patients were more refractory to steroids (0dds Ratio:3.6 ;95% CI:1.01–13.2, p:0.047). Response to rescue infliximab was similar (Odds Ratio:0.45 ;95% CI:0.13–1.5, p:0.215), even in patients failing standard dosed infliximab. High CRP levels (4.89 mg/dl vs 2.64 mg/dl, p:0.014) and low albumin levels (3.4 g/dl vs 3.9 g/dl, p:0.013) were predictive of colectomy in contrast to endoscopic severity and disease extent. Conclusion ASUC remains a therapeutic challenge in the modern era, with considerable refractoriness to medical therapy and colectomy risk: 50% of our group of ASUC patients responded to steroids and 22% underwent colectomy within two years of follow-up. High inflammatory burden, depicted by high CRP values and hypoalbuminemia can predict need for colectomy. Bio-exposed patients were more refractory to steroids but they showed comparable response to intensified infliximab, so they can be managed in the same way, at least until therapy with small molecules proves more efficient by future studies.

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A comparison of long-term healthcare utilization and costs in patients with acute severe ulcerative colitis receiving infliximab versus early colectomy

Therapeutic Advances in Chronic Disease ◽

10.1177/2040622319825595 ◽

2019 ◽

Vol 10 ◽

pp. 204062231982559 ◽

Cited By ~ 1

Author(s):

Abhinav Vasudevan ◽

Asiri Arachchi ◽

Cian Scanlon ◽

Jarrod Greenhalgh ◽

Daniel R. Van Langenberg

Keyword(s):

Ulcerative Colitis ◽

Length Of Stay ◽

Healthcare Utilization ◽

Healthcare Costs ◽

Initial Therapy ◽

Severe Ulcerative Colitis ◽

Necrosis Factor ◽

Steroid Refractory

Background: Early intervention for acute severe ulcerative colitis (ASUC) improves outcomes. Outcomes and healthcare costs for an infliximab-first and colectomy-first approach were compared. Methods: This single-center retrospective cohort study of inpatients with steroid-refractory ASUC who received infliximab 5 mg/kg (1–3 doses without maintenance) or initial colectomy between 2004 and 2014 assessed long-term healthcare utilization and direct costs following infliximab or colectomy, using admission coding data until 31 December 2016. Results: A total of 118 patients received either infliximab ( n = 85, 72%) or colectomy ( n = 33, 28%) as initial therapy, with 35(41%) patients eventually requiring colectomy post-infliximab (median 213 days, range [6, 3739]). Median follow up was 7 years [0, 14]. Following infliximab for ASUC, 44% of patients then received antitumor necrosis factor maintenance. After ASUC therapy, length of stay and number of admissions did not significantly differ between groups but higher numbers of complications prompting readmission occurred in the colectomy group (median 4 versus 1, p < 0.001). There were no differences in admissions or total length of stay for patients who had received infliximab first then colectomy versus those treated with colectomy first (median 7.0 versus 4.0, 41.5 days versus 29 days, respectively, each p > 0.05). Total costs were lower at 6 months (mean AUD17,662 versus AUD24,852, p = 0.003), yet were similar at 7 years following an infliximab compared with colectomy approach (AUD72,834 versus AUD59,557, p = 0.23). After infliximab, costs were significantly higher at 7 years with biologic rather than immunomodulator-only maintenance therapy (AUD109,365 versus AUD47,842, p < 0.01). Conclusions: In support of current practice, infliximab salvage in steroid-refractory ASUC achieved reduced short-term healthcare costs compared with initial colectomy, though long-term costs were not significantly different.

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Living with Ulcerative Colitis in Japan: Biologic Persistence and Health-Care Resource Use

Inflammatory Intestinal Diseases ◽

10.1159/000519123 ◽

2021 ◽

pp. 1-13

Author(s):

Danielle Bargo ◽

Theo Tritton ◽

Joseph C. Cappelleri ◽

Marco DiBonaventura ◽

Timothy W. Smith ◽

...

Keyword(s):

Ulcerative Colitis ◽

Health Care ◽

Negative Binomial ◽

Biologic Therapy ◽

Cohort Analysis ◽

Japanese Patients ◽

Health Care Resource ◽

Administrative Database ◽

Outpatient Visits

Objective: The aim of the study was to improve understanding of adherence and persistence to biologics, and their association with health-care resource utilization (HCRU), in Japanese patients with moderate to severe ulcerative colitis (UC). Methods: Data were from Medical Data Vision, a secondary care administrative database. A retrospective, longitudinal cohort analysis was conducted of data from UC patients initiating biologic therapy between August 2013 and July 2016. Data collected for 2 years prior (baseline) and 2 years after (follow-up) the index date were evaluated. Patients completing biologic induction were identified, and adherence/persistence to biologic therapy calculated. HCRU, steroid, and immunosuppressant use during baseline and follow-up were assessed. Biologic switching during the follow-up was evaluated. Descriptive statistics (e.g., means and proportions) were obtained and inferential analyses (from Student’s t tests, Fisher’s exact tests, χ2 tests, the Cox proportional hazard model, and negative binomial regression) were performed. Results: The analysis included 649 patients (adalimumab: 265; infliximab: 384). Biologic induction was completed by 80% of patients. Adherence to adalimumab was higher than that to infliximab (p < 0.001). Persistence at 6, 12, 18, and 24 months was higher with infliximab than with adalimumab (p < 0.05). Overall, gastroenterology outpatient visits increased, and hospitalization frequency and duration decreased, from baseline to follow-up. UC-related hospitalizations were fewer and shorter, and endoscopies fewer, in persistent than in nonpersistent patients, although persistent patients made more outpatient visits than nonpersistent patients. Hospitalization duration was lower in persistent than nonpersistent patients. Approximately 50% of patients received an immunosuppressant during biologic therapy; 5% received a concomitant steroid during biologic therapy. Overall, 17% and 3% of patients, respectively, received 2nd line and 3rd line biologics. Conclusions: Poor biologic persistence was associated with increased non-medication-associated HCRU. Effective treatments with high persistence levels and limited associated HCRU are needed in UC.

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