The Burden of Work Productivity and Activity Impairment in Patients with Psoriasis, Psoriatic Arthritis, Ulcerative Colitis, and Crohn's Disease.

BACKGROUND: Comparisons among autoimmune diseases enable understanding of the burden and factors associated with work productivity loss and impairment. AIMS: The objective was to compare work productivity and activity and associated factors among patients with inflammatory bowel diseases and other autoimmune conditions. METHODS: This cross-sectional study included employed, adult patients (age 20-64 years) in the CorEvitas Inflammatory Bowel Disease, Psoriasis, and Psoriatic Arthritis/Spondyloarthritis Registries between 5/2017 and 6/2020. Any patient-reported impairment on four domains of the Work Productivity and Activity Index (WPAI) was collected across registries. Prevalence for each autoimmune disease was reported and stratified by disease activity using direct age-sex-standardization. Factors associated with the presence of any WPAI were identified in logistic regression models. RESULTS: A total of 7,169 patients with psoriasis (n = 4,768, 67%), psoriatic arthritis (n = 1,208, 17%), Crohn's disease (CD, n = 621, 9%), and ulcerative colitis (UC, n = 572, 8%) met inclusion criteria. Among patients not in remission across all disease cohorts, the age-sex-standardized prevalence of any presenteeism, work productivity loss, and activity impairment ranged from 54 to 97%. Patients with CD in remission had higher standardized prevalence of presenteeism (53% [48-57%]) and work productivity loss (54% [49-59%]), compared to those from other cohorts (presenteeism [range: 33-39%] and work productivity loss [range: 37-41%]). For all WPAI domains, the strongest adjusted associations were for moderate to severe disease activity and psychosocial symptoms. CONCLUSIONS: Patients with moderate to severe disease activity reported the highest WPAI burden. However, patients in remission or mild disease activity also report some WPAI burden, emphasizing a multidisciplinary treatment approach to improve work productivity loss and impairment.

Prevalence and Factors Associated With Patient-Clinician Discordance Among Patients With Rheumatoid Arthritis Initiating Advanced Therapy.

OBJECTIVE: To describe and identify associated factors for patient-clinician discordance of disease assessment at biologic or Janus kinase inhibitor (JAKi) initiation and over 12 months following initiation in patients with rheumatoid arthritis (RA) from a US RA registry. METHODS: Analyses included CorEvitas RA Registry patients who initiated their first biologic or JAKi on or after February 1, 2015, and had 6- and 12-month follow-up visits. Positive discordance was defined as patient global assessment (visual analog scale [VAS-100]) minus physician's global assessment (VAS-100) equal to 30 points or more. Persistent discordance was defined as positive discordance at all three visits. Mixed-effects logistic regression was used to determine risk factors for positive discordance at initiation and for persistent discordance. RESULTS: Among 2227 first-time biologic/JAKi-initiating patients, 613 had both follow-up visits available and were included in initiation visit analyses, and of these, 163 had positive discordance at initiation and were included in persistent discordance analyses. About 30% of all patients had positive discordance at any visit, and one third of these (10% total) were persistent at all three visits. Multivariable analyses revealed that worse scores on the Clinical Disease Activity Index, greater patient-reported pain and fatigue, and greater functional impairment were associated with positive discordance at the time of therapy initiation. Being disabled versus working full-time and being female were associated with higher odds and having Medicare versus no insurance was associated with lower odds of having persistent positive discordance. CONCLUSION: Results suggest positive discordance is common among real-world patients with RA initiating their first biologic or JAKi. The identified risk factors associated with patient-clinician discordance will help clinicians foster a more patient-centric discussion in treatment decisions.

Characteristics and 6-Month Outcomes in Patients with Rheumatoid Arthritis Initiating Infliximab Biosimilar IFX-dyyb in a Real-World Setting.

INTRODUCTION: Real-world studies describing biosimilar initiation or switching in patients with rheumatoid arthritis (RA) are limited. The aim of this study was to assess treatment patterns and effectiveness of real-world patients with RA initiating infliximab biosimilar IFX-dyyb (CT-P13; Inflectra®) in the USA. METHODS: This observational study evaluated patients with RA from the CorEvitas RA Registry who initiated IFX-dyyb and had Clinical Disease Activity Index (CDAI) recorded at baseline and 6 months. The primary outcome was reaching low disease activity (LDA; CDAI ≤ 10) at 6 months in patients with moderate or high disease activity (CDAI > 10) at baseline. Secondary outcomes were change at 6 months in CDAI and certain patient-reported outcomes (PROs). Patient data were stratified by prior treatment: biologic/targeted synthetic disease-modifying antirheumatic drug (tsDMARD)-naïve, reference infliximab (IFX-REF) or IFX biosimilar, or a non-IFX biologic or tsDMARD. RESULTS: Of 318 patients initiating IFX-dyyb, 176 had baseline and 6-month CDAI scores; 73 (41%) switched from IFX, 61 (35%) switched from another non-IFX/biologic/tsDMARD, 32 (18%) were naïve to biologics/tsDMARDs, and 10 (6%) switched from an IFX biosimilar. Among patients with moderate or high disease activity at baseline, 32.9% (95% CI 22.9, 42.9) achieved LDA at 6 months. Mean 6-month change from baseline in CDAI was - 1.8 (95% CI - 3.3, - 0.3) overall; - 4.7 (- 7.6, - 1.7) in patients who switched from a non-IFX biologic/tsDMARD, - 4.1 (- 7.8, - 0.3) in biologic/tsDMARD-naïve patients, and 1.1 (- 0.4, 2.6) in patients who switched from IFX-REF/IFX biosimilar. Other clinical outcomes/PROs improved at 6 months. Of the IFX-dyyb initiators, 68% remained on IFX-dyyb at 6 months. CONCLUSION: In this real-world population of patients with RA initiating IFX-dyyb, the majority switched from IFX-REF or a non-IFX biologic/tsDMARD. CDAI remained stable in patients switching from IFX-REF/IFX biosimilar and improved in patients switching from a non-IFX biologic/tsDMARD and in biologic/tsDMARD-naïve patients.

Infliximab is an effective treatment for rheumatoid arthritis (RA). Biosimilars­biologic drugs designed to be very similar to the originator products­are now available that may be more affordable with matching efficacy and safety. IFX-dyyb is a US Food and Drug Administration-approved infliximab biosimilar but little is known about its use in real-world clinical practice in patients with RA in the USA. This study used data from a large observational registry to look at treatment patterns and effectiveness of IFX-dyyb in adults with RA. One hundred and seventy-six patients were included who had data available at both baseline and at 6 months. Most patients (47%) switched to IFX-dyyb from the originator infliximab or another infliximab biosimilar; 35% switched from another RA treatment, and 18% were new to treatment. Six months after starting IFX-dyyb, 68% of patients were still receiving treatment. A measure of clinical disease activity remained stable in patients who switched from originator infliximab or another biosimilar, while this measure improved in patients switching to IFX-dyyb from other treatments or starting treatment for the first time. Other clinical measures and patient-reported outcomes such as pain and fatigue also improved over 6 months with IFX-dyyb. This real-world study of patients with RA initiating IFX-dyyb in the USA adds to our knowledge of the use of biosimilars in this patient population.

Treatment Patterns and Effectiveness of Tofacitinib in Patients Initiating Therapy for Rheumatoid Arthritis: Results From the CorEvitas Rheumatoid Arthritis Registry.

OBJECTIVE: This real-world analysis assessed baseline demographics/characteristics and treatment patterns/effectiveness in patients with rheumatoid arthritis (RA) initiating tofacitinib (TOF) in the US CorEvitas RA Registry. METHODS: The primary analysis of this study included patients with RA initiating TOF with a 12-month follow-up visit from November 2012 to January 2021. Outcomes included baseline demographics/characteristics and TOF initiation/discontinuation reasons, treatment patterns, and effectiveness (disease activity and patient-reported outcomes [PROs] at 12 months); the primary effectiveness outcome was Clinical Disease Activity Index low disease activity (CDAI LDA). All data, analyzed descriptively, were stratified by TOF regimen (monotherapy vs combination therapy), line of therapy (second- to fourth-line), time of initiation (2012-2014, 2015-2017, or 2018-2020), and dose (5 mg twice daily vs 11 mg once daily). RESULTS: Of 2874 patients with RA who initiated TOF, 1298 had a qualifying 12-month follow-up visit; of these, 43.1% were monotherapy and 66.5% were fourth-line therapy. Overall, tumor necrosis factor inhibitors (40.8%) were the most common treatment immediately prior to TOF initiation. The most common reason for TOF initiation (among those with a reason) was lack/loss of efficacy of prior treatment (67.7%). Overall, at 12 months, 31.9% and 10.1% had achieved CDAI LDA and remission, respectively; 22.4%, 10.4%, and 5% had achieved ≥ 20%, ≥ 50%, and ≥ 70% improvement in modified American College of Rheumatology core set measures, respectively; and improvements in PROs were observed. Effectiveness was generally similar across TOF stratifications. CONCLUSION: TOF effectiveness (CDAI LDA) was observed in a US real-world setting of patients with RA regardless of TOF regimen, line of therapy, time of initiation, and dose. (ClinicalTrials.gov: NCT04721808).

Comparative effectiveness of abatacept versus TNF inhibitors in rheumatoid arthritis patients who are ACPA and shared epitope positive.

BACKGROUND: The HLA-DRB1 shared epitope (SE) is a risk factor for the development of rheumatoid arthritis (RA) and the production of anti-citrullinated protein antibodies (ACPAs) in RA patients. Our objective was to examine the real-world effectiveness of abatacept versus tumor necrosis factor inhibitors (TNFi) in patients with RA who were SE and anti-cyclic citrullinated peptide antibody (anti-CCP3) positive. METHODS: Abatacept or TNFi initiators who were SE + and anti-CCP3+ (> 20 U/mL) at or prior to treatment and had moderate or high CDAI score (> 10) at initiation were identified. The primary outcome was mean change in CDAI score over six months. Analyses were conducted in propensity score (PS)-trimmed and -matched populations overall and a biologic-experienced subgroup. Mixed-effects models were used. RESULTS: In the overall PS-trimmed (abatacept, n = 170; TNFi, n = 157) and PS-matched cohorts (abatacept, n = 111; TNFi, n = 111), there were numerically greater improvements in mean change in CDAI between abatacept and TNFi but were not statistically significant. Similar trends were seen for biologic-experienced patients, except that statistical significance was reached for mean change in CDAI in the PS-trimmed cohort (abatacept, 12.22 [95% confidence interval (95%CI) 10.13 to 14.31]; TNFi, 9.28 [95%CI 7.08 to 11.48]; p = 0.045). CONCLUSION: In this real world cohort, there were numerical improvements in efficacy outcomes with abatacept over TNFi in patients with RA who were SE + and ACPA+, similar to results from a clinical trial population The only statistically significant finding after adjusting for covariates was greater improvement in CDAI with abatacept versus TNFi in the bio-experienced PS-trimmed cohort..

Comparative effectiveness of abatacept versus TNF inhibitors in rheumatoid arthritis patients who are ACPA and shared epitope positive

Abstract Background The HLA-DRB1 shared epitope (SE) is a risk factor for the development of rheumatoid arthritis (RA) and the production of anti-citrullinated protein antibodies (ACPAs) in RA patients. Our objective was to examine the real-world effectiveness of abatacept versus tumor necrosis factor inhibitors (TNFi) in patients with RA who were SE and anti-cyclic citrullinated peptide antibody (anti-CCP3) positive. Methods Abatacept or TNFi initiators who were SE + and anti-CCP3+ (> 20 U/mL) at or prior to treatment and had moderate or high CDAI score (> 10) at initiation were identified. The primary outcome was mean change in CDAI score over six months. Analyses were conducted in propensity score (PS)-trimmed and -matched populations overall and a biologic-experienced subgroup. Mixed-effects models were used. Results In the overall PS-trimmed (abatacept, n = 170; TNFi, n = 157) and PS-matched cohorts (abatacept, n = 111; TNFi, n = 111), there were numerically greater improvements in mean change in CDAI between abatacept and TNFi but were not statistically significant. Similar trends were seen for biologic-experienced patients, except that statistical significance was reached for mean change in CDAI in the PS-trimmed cohort (abatacept, 12.22 [95% confidence interval (95%CI) 10.13 to 14.31]; TNFi, 9.28 [95%CI 7.08 to 11.48]; p = 0.045). Conclusion In this real world cohort, there were numerical improvements in efficacy outcomes with abatacept over TNFi in patients with RA who were SE + and ACPA+, similar to results from a clinical trial population The only statistically significant finding after adjusting for covariates was greater improvement in CDAI with abatacept versus TNFi in the bio-experienced PS-trimmed cohort. .

Brentuximab vedotin with AVD for stage II-IV HIV-related Hodgkin lymphoma (AMC 085): phase 2 results from an open-label, single arm, multicentre phase 1/2 trial.

BACKGROUND: Brentuximab vedotin in combination with doxorubicin, vinblastine, and dacarbazine (AVD) is approved in the upfront setting for advanced stage classical Hodgkin lymphoma (cHL). People living with HIV have been excluded from these studies. We aimed to understand the activity and safety of brentuximab vedotin-AVD in people living with HIV diagnosed with Hodgkin lymphoma, while focusing on HIV disease parameters and antiretroviral therapy (ART) interactions. METHODS: We present the phase 2 portion of a multicentre phase 1/2 study. Eligible patients were 18 years or older, had untreated stage II-IV HIV-associated cHL (HIV-cHL), a Karnofsky performance status of more than 30%, a CD4+ T-cell count of 50 cells per µL or more, were required to take ART, and were not on strong CYP3A4 or P-glycoprotein inhibitors. Patients were treated intravenously with 1·2 mg/kg of brentuximab vedotin (recommended phase 2 dose) with standard doses of AVD for six cycles on days 1 and 15 of a 28-day cycle. The primary endpoint of the phase 2 portion was 2-year progression-free survival (PFS), assessed in all eligible participants who began treatment. Accrual has been completed. This trial is registered at ClinicalTrials.gov, NCT01771107. FINDINGS: Between March 8, 2013, and March 7, 2019, 41 patients received study therapy with a median follow up of 29 months (IQR 16-38). 34 (83%) of 41 patients presented with stage III-IV and seven (17%) with stage II unfavourable HIV-cHL. 37 (90%) of 41 patients completed therapy, all 37 of whom achieved complete response. The 2-year PFS was 87% (95% CI 71-94) and the overall survival was 92% (78-97). The most common grade 3 or worse adverse events were peripheral sensory neuropathy (four [10%] of 41 patients), neutropenia (18 [44%]), and febrile neutropenia (five [12%]). One treatment-related death was reported, due to infection. INTERPRETATION: Brentuximab vedotin-AVD was highly active and had a tolerable adverse event rate in HIV-cHL and is an important therapeutic option for people with HIV-cHL. The complete reponse rate is encouraging and is possibly related to a unique aspect of HIV-cHL biology. Upcoming 5-year data will evaluate the sustainability of the outcomes obtained. FUNDING: National Institutes of Health and National Cancer Institute.

Comparative Effectiveness of Abatacept vs. Tofacitinib in Rheumatoid Arthritis Patients who are CCP.

INTRODUCTION: Currently there is limited data to drive clinical decision making regarding  the choice of biologic/targeted synthetic disease-modifying antirheumatic drugs (DMARD); thus, head-to-head comparisons are needed to help guide prescribing. In recent years, significant advancements have helped clarify the mechanistic basis of the clinical associations of autoantibodies in rheumatoid arthritis (RA). This study evaluated the effectiveness of abatacept versus tofacitinib in anti-cyclic citrullinated peptide (CCP+) patients with rheumatoid arthritis (RA). METHODS: CorEvitas (formerly known as CORRONA) Registry patients aged ≥ 18 years, who were CCP+ before initiating abatacept or tofacitinib (December 2012 onwards through October 2019), had 6-month follow-up data (baseline and 6-month Clinical Disease Activity Index [CDAI]), and were not in remission at index were included. Patients were frequency matched 1:1 by prior biologic use before propensity score matching (PSM). Primary (mean change [D] in CDAI) and secondary outcomes 6 months after index were compared using mixed-effects models adjusted for variables that remained unbalanced after PSM. RESULTS: Following PSM, most baseline characteristics for 291 patient pairs were well balanced between treatments, although fewer patients initiating abatacept versus tofacitinib received prior non-TNFi biologic DMARDs, and patients initiating abatacept versus tofacitinib had a higher physician global assessment score, patient-reported fatigue, and modified Health Assessment Questionnaire (mHAQ). In adjusted analyses, there were no significant differences in mean [D] from baseline in CDAI at 6 months with abatacept versus tofacitinib (P = 0.936). Patients naïve for b/tsDMARDs initiating abatacept had a numerically greater mean [D] in CDAI at 6 months versus tofacitinib, although this difference was not statistically significant (P = 0.662). There were no significant differences for any secondary outcomes. CONCLUSIONS: In adjusted analyses, CCP+ patients with RA initiating treatment with abatacept versus tofacitinib did not show a statistically significant difference in reducing disease activity or improving patient-reported outcomes.

Characteristics of Patients with Crohn's Disease With or Without Perianal Fistulae in the CorEvitas Inflammatory Bowel Disease Registry.

BACKGROUND: There are limited real-world data characterizing perianal fistulae in patients with Crohn's disease (CD). AIM: To describe characteristics of patients with CD with and without perianal fistulae. METHODS: In this cross-sectional study, characteristics, treatment history, and health outcomes of patients with CD enrolled in the CorEvitas IBD Registry were described according to perianal fistula status (current/previous or none). RESULTS: Eight hundred and seventy-eight patients were included. Compared with patients with no perianal fistulae (n = 723), patients with current/previous perianal fistulae (n = 155) had longer disease duration since CD diagnosis (mean 16.5 vs 12.3 years; difference 4.3 years; 95% CI, 2.0, 6.6) and fewer had Harvey-Bradshaw Index scores indicative of remission (0-4, 56.8% vs 69.6%; difference - 12.9%; 95% CI, - 21.6, - 4.2). More patients with current/previous fistulae reported a history of IBD-related emergency room visits (67.7% vs 56.1%; difference 11.6%; 95% CI, 3.4, 19.8), hospitalizations (76.1% vs 58.4%; difference 17.7%; 95% CI, 10.1, 25.4), and surgeries (59.4% vs 27.7%; difference 31.7%; 95% CI, 23.3, 40.1), and a history of treatment with tumor necrosis factor inhibitors (81.3% vs 60.7%; difference 20.6%; 95% CI, 13.5, 27.7), immunosuppressants (51.6% vs 31.2%; difference 20.4%; 95% CI, 11.9, 29.0), and antibiotics (50.3% vs 23.7%; difference 26.6%; 95% CI, 18.2, 35.1) than patients without perianal fistulae. CONCLUSIONS: Patients with CD with current/previous perianal fistulae have more symptomatic experiences of disease, higher medication use, hospitalization rates, and emergency room visits than patients without perianal fistulae. Interventions to prevent/reduce risk of developing fistulae may help improve outcomes in CD.

Change in Urgency Status Among Ulcerative Colitis Patients: Understanding a Potential Unmet Patient Need From the CorEvitas Inflammatory Bowel Disease Registry.

Background and Aims: Fecal urgency is a common symptom of Ulcerative Colitis (UC). We explored the association between changes in fecal urgency for patient characteristics and evaluated the association between change in treatment and change in fecal urgency. Methods: The study cohort (n = 400) included UC patients in the CorEvitas Inflammatory Bowel Disease Registry between May 3, 2017 and September 1, 2020. Fecal urgency was defined using the Simple Clinical Colitis Activity Index. Urgency groups were formed by urgency at enrollment and 6-month follow-up visit: no persistent urgency at both visits (NPU); change from urgency to no urgency (UN); change from no urgency to urgency (NU); and persistent urgency at both visits (PU). Descriptive statistics were used to explore between urgency group differences at baseline and Kaplan-Meier curves to compare time to first treatment change. Results: Groups included NPU (n = 175), UN (n = 86), NU (n = 56), and PU (n = 83). At enrollment, we found differences between groups for increased depression, anxiety, prior infections, diabetes; also, greater fatigue, pain, work impairment, work hours affected, and daily activities impacted. Compared to NPU patients, UN, NU, and PU patients were more likely to change treatment between enrollment and 6-month follow-up visit, and a higher proportion of UN, NU, and PU patients on a biologic at enrollment changed treatment vs the NPU group between both visits. Conclusion: Among real-world UC patients, fecal urgency status is associated with increased comorbidities and worse patient-reported outcomes and significant differences in change of treatment and time to treatment change. Urgency at any time point diminishes quality of life and may be a sign of inadequate therapy, which often is an indication to switch therapy.