Real world evidence of the association between medication and life expectancy in elderly inflammatory bowel disease: a population-based cohort study

Background Life expectancy in people with inflammatory bowel disease (IBD) has increased but remains shorter than in people without IBD. We describe the life expectancy associated with IBD therapies among the growing number of older adults living with IBD. Methods Older adults (≥ 65 years) with IBD were identified from population-based health administrative data using a validated algorithm. Life expectancy on patients’ 65th birthday, stratified by sex, was calculated using a period life table approach from age- and sex-specific mortality rates among patients receiving immunomodulator monotherapy, biologic monotherapy, combination therapy, mesalamine, systemic steroids, and no therapy. Results Among 28,260 older adults with IBD (239,125 person-years of follow-up), life expectancy at 65 years was longest for patients taking mesalamine (females: 22.1 years, 95% CI 21.8–22.5; males: 19.6 years, 95% CI 19.3–20.0) and shortest for patients taking steroids (females: 11.7 years, 95% CI 11.0–12.4; males 10.3 years, 95% CI 9.7–10.8). Life expectancy was similar for patients receiving immunomodulator monotherapy and biologic monotherapy. Immunomodulator monotherapy was associated with a reduction in life expectancy compared to combination therapy by 5.1 (95% CI 2.3–7.8) in females and 2.8 years (95% CI 0.1–5.5) in males. Conclusions Life expectancy varies across therapies used for IBD, with differences likely arising from a combination of medication effectiveness, safety profiles, disease severity, and comorbid conditions. These considerations should be balanced when deciding on a therapeutic approach for the management of IBD in older adults.

Triple therapy with adalimumab, ustekinumab and methotrexate for induction of remission in moderate to severe ileocolonic Crohn’s disease with upper gastrointestinal involvement in a biologic-experienced individual

Induction of remission in biologic-experienced individuals with moderate to severe Crohn’s disease (CD) can be a challenge. We hereby present a case of CD with secondary non-response to infliximab. Adding methotrexate and switching to ustekinumab plus methotrexate did not stop the inflammatory process. Therefore, combination therapy with two classes of biologics consisting of ustekinumab and adalimumab plus methotrexate was initiated. He achieved clinical remission in 4 weeks and remained on triple therapy for 6 months which was subsequently tailored to adalimumab/methotrexate combination therapy due to insurance restriction on ustekinumab. He remained in remission for the duration of follow-up, 14 months after initiation of triple therapy and 8 months after switching to methotrexate/adalimumab biologic monotherapy. Triple therapy with anti-TNF, IL-12/23 inhibitor and methotrexate could potentially be an option for induction of remission in biologic-experienced individuals with good initial clinical response to anti-TNF agents.

Treatment patterns in rheumatoid arthritis patients newly initiated on biologic and conventional synthetic disease-modifying antirheumatic drug therapy and enrolled in a North American clinical registry

Background Understanding the evolving treatment patterns in patients with rheumatoid arthritis (RA) is important for rheumatologists to make the best practice decisions and optimize treatment. Here, we describe treatment patterns among patients newly initiated on biologic and/or nonbiologic RA therapy over time after enrollment in the US Corrona RA registry. Methods This was a retrospective, cohort study of adult patients with RA enrolled in the Corrona RA registry. Patients were included in this study if they initiated therapy with conventional synthetic disease-modifying antirheumatic drug (csDMARD) monotherapy, TNF inhibitor (TNFi) monotherapy, other (non-TNFi) biologic monotherapy, or combination therapy (index therapy); initiated therapy between January 1, 2004, and December 31, 2015 (index date), after enrollment in the Corrona RA registry; had at least 6 months of follow-up time after the index date; and had at least one follow-up visit. Time periods of interest were based on the year of index therapy initiation: 2004–2007, 2008–2011, and 2012–2015. Results This study included 8027 patients. csDMARD monotherapy and TNFi + csDMARD combination therapy were the most common index therapies in the registry (39.9% and 44.9%, respectively, in the 2004–2007 period; 38.6% and 38.2%, respectively, in the 2008–2011 period; and 35.2% for both in the 2012–2015 period). At therapy initiation, a higher proportion of patients who initiated other biologics, whether as monotherapies (54.0%) or in combination with csDMARD (49.9%), had high disease activity than those who initiated csDMARD monotherapy (28.4%). For 2012–2015 vs 2004–2007 and 2008–2011 periods, persistence on a given therapy appeared to decrease for the TNFi monotherapy cohort (48.2% vs 64.3% and 52.4%) and other biologic monotherapy cohort (52.3% vs 71.4% and 54.5%) over 12 months; switching from one therapy to another was common in the Corrona RA registry. Conclusions Increased switching from one therapy to another and decreased time on a given therapy was observed in the Corrona RA registry in the 2012–2015 period. This observation is most likely due to the increased availability of additional treatment options and/or the change in clinical focus, particularly the emphasis on achievement of treat-to-target goals of remission or low disease activity along with more aggressive treatment.

POS1301 DRUG SURVIVAL OF BIOLOGICS WITH RESPECT TO COMBINATION WITH METHOTREXATE IN TREATMENT OF POLYARTICULAR JIA

Background:In polyarticular juvenile idiopathic arthritis (pJIA) biologic therapies are often combined with methotrexate (MTX). This combination was shown to increase efficacy in adult rheumatoid arthritis patients. MTX may also have a protective effect on the formation of anti-drug antibodies and thus may prolong drug survival. In pJIA, there are few and sometimes controversial data available.Objectives:To compare the effect of combination treatment with MTX on discontinuation due to inefficacy and on drug survival discontinuation of biologics approved for first line treatment of pJIA.Methods:Patients from the German BIKER registry with their first treatment course with Adalimumab, Etanercept, Golimumab or Tocilizumab were selected. Rates of ineffectiveness-related withdrawal were analysed and compared using χ2-test, Wald-test and Kaplan-Meier analysis of patients receiving biologic monotherapy or concomitant methotrexate. Cases were censored if MTX was discontinued before the biologic.Results:2173 pJIA patients were identified who for the first time received a biologic. Etanercept (ETA) was by far the most frequently used biologic for first line biologic treatment in pJIA (77%) followed by Adalimumab (ADA, 16%). Patients on Golimumab (GOL) received most frequently a combination with MTX (86.5%), while patients on Tocilizumab (TOC) had the lowest rate of combination treatment (53%).ETA/ADA/GOL/TOC was given as monotherapy in 500(30%)/89(26%)/5(13.5%)/46(47%) and combined with MTX in 1179 (70%)/259(74%)/32(86.5%)/51(53%) cases. More patients with rheumatoid-factor negative (54 vs 50%; p=0.04) and rheumatoid-factor positive pJIA (13 vs 10%, p=0.04) received combination with MTX, while more patients in the monotherapy cohort had extended oligoarthritis (40 vs 32%, p<0.001). Patients with MTX had a shorter disease duration (4 vs 5.5years, p<0.001) and received concomitant steroid more often (34 vs 24%), p<0.001). There was no statistical difference regarding disease activity parameters (active joint count, patient assessment and physician assessment of disease activity, ESR, CRP, CHAQ-DI, JADAS10). Discontinuation due to ineffectiveness was reported for ETA/ADA/GOL/TOC in 20%/18%/14%/28% of patients, respectively in 3.7/4.9/6/10.5 patients/100 treatment years. Thus discontinuation due to inefficacy was reported less frequently with ETA compared to ADA (p=0.046) and TOC (p<0.001) and with ADA compared to TOC (p<0.001).Patients on ETA and ADA had a slightly, but not statistically significant lower rate of withdrawal for ineffectiveness if on methotrexate (Figure 1). There was no difference regarding baseline disease activity parameters in patients with ETA/ADA monotherapy compared with combination with MTX, apart from patients with ETA+MTX receiving more often systemic steroids at baseline (36vs 24%,p<0-001). For both GOL and TOC treatment, no baseline differences in disease activity between cohorts with monotherapy and MTX combination could be shown. The combination with MTX led to significantly lower rates of discontinuation due to inefficacy (p<0.05) with GOL and TOC (Figure 1).Conclusion:Patients with pJIA mostly were treated with a combination of the biologic and MTX rather than with biologic monotherapy. Treatment was discontinued due to lack of efficacy in 14% to 28%. No statistically significant effect of combination treatment with MTX versus monotherapy could be observed regarding the rate of treatment failures in patients treated with ETA or ADA. However, combination treatment with MTX significantly prolonged the survival of GOL and TOC in patients with polyarticular JIA. The results are limited by low patient numbers in the GOL cohort and possible bias by JIA category.Figure 1.Kaplan Meier plot of drug survival in patients with monotherapy or with combination with MTX of the indicated biologicDisclosure of Interests:Gerd Horneff Speakers bureau: MSD, Grant/research support from: Pfizer, Roche, Chugai, MSD, Daniel Windschall: None declared, Kirsten Minden Speakers bureau: Pfizer, Abbvie, Grant/research support from: Pfizer, Toni Hospach: None declared, Frank Dressler: None declared, Frank Weller-Heinemann: None declared, Boris Huegle: None declared, Ivan Foeldvari Speakers bureau: Pfizer, Ariane Klein: None declared

A Systematic Review of Efficacy and Safety of Monotherapy and Combination Therapy With Biologic for Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis

Background Biologic drugs have the potential to halt the progression of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) by decreasing concentrations of tumor necrosis factor-α, a cytokine implicated in epithelial cell death. The objective of this systematic review is to investigate the efficacy and safety of biologic monotherapy and combination therapy for SJS/TEN. Methods MEDLINE and EMBASE in OVID were searched on October 28, 2020. Inclusion criteria were original studies containing human participants diagnosed with SJS/TEN and treated with biologics. Studies were excluded if they were literature reviews, systematic reviews, letters to the editor, or conference abstracts. Results The 38 articles reviewed included 27 (71.1%) case reports, 6 (15.8%) case series, 3 (7.9%) retrospective reviews, and 2 (5.3%) RCTs. The age range of the included studies was 2 to 85 years, the mean age was 46.4 years. The mean body surface (BSA) across the 38 included articles was 31.0%. The average actual mortality reported within the 38 included articles was 9.2%. Both biologic monotherapy and combination therapy were associated with improved outcomes in SJS/TEN. Furthermore, anti TNF-alpha therapy, specifically etanercept, showed improved outcomes as monotherapy. Conclusions Overall, reviewed studies presented a strong case for biologic treatment, both monotherapy and combination use, in SJS/TEN treatment. Based on the number of fatal adverse events observed, biologic monotherapy may be safer compared to combination therapy. Further research with a larger sample size and a randomized control trial design is required.

Effectiveness and Safety of Combining Tofacitinib with a Biologic in Patients with Refractory Inflammatory Bowel Diseases

ABSTRACT AND KEY WORDSBackgroundOne therapeutic option with limited data among patients with active moderate-to-severe ulcerative colitis (UC) and Crohn’s disease (CD) despite biologic monotherapy is using a combination of a biologic with Tofacitinib (TBT). Our aim was to examine the effectiveness and safety of TBT in this subset of patients.MethodsData of IBD patients at 2 referral centers on TBT were extracted. The primary outcome was clinical response (>50% reduction in symptoms) at week 8 and/or 16 determined by Physician Global Assessment. Secondary outcome was clinical remission (resolution of symptoms), corticosteroid-free clinical response and remission, normalization of CRP and endoscopic/radiographic response and remission. Adverse events (AEs) including any abnormal lipid profile or surgical complications were also assessed.ResultsThirty-five patients (25UC, 10CD) were included. Biologics combined with tofacitinib were vedolizumab (68.6%), ustekinumab (17.1%), and infliximab (14.3%) and the median follow-up duration was 4 months. A majority (57.2%) had failed at least two biologics prior to starting TBT. At weeks 8 and/or 16, 37.1% achieved clinical response with 5.7% in clinical remission. Among the 23 patients with endoscopically/radiographically active disease at baseline, 56.5% had endoscopic/radiographic response and 34.8% achieved remission. Three AEs occurred in 2 (5.7%) patients, with an IR of 20.5 (15.0–47.2)/100PYF. No VTE and herpes zoster was reported.ConclusionsTBT is effective at inducing endoscopic/radiographic response and a modest clinical response in UC and CD patients with active clinical symptoms despite prior biologic monotherapy. No new safety signals were detected beyond those reported with tofacitinib monotherapy.