ABSTRACT
BackgroundPain is a debilitating symptom of ankylosing spondylitis (AS) that negatively affects patients' lives. Upadacitinib (UPA), a Janus kinase inhibitor approved for the treatment of AS and other inflammatory diseases, showed significant efficacy vs placebo (PBO) in the phase 2/3 SELECT-AXIS 1 study in patients with AS who were biologic-naive and in the phase 3 SELECT-AXIS 2 study in patients with active AS who had an inadequate response (IR) to biological therapy [1,2]. Improvement in pain outcomes with UPA was also previously demonstrated in the SELECT-AXIS 1 study [3].ObjectivesThe objective of this post-hoc analysis of SELECT-AXIS 2 was to evaluate the efficacy of UPA vs PBO on multiple pain assessments through 14 weeks in patients with IR to a biologic disease-modifying antirheumatic drug (bDMARD-IR).MethodsSELECT-AXIS 2 (NCT04169373) enrolled adults with active AS with IR to biological therapy, including patients who discontinued biologics due to lack of efficacy or intolerance [1]. Patients were randomized 1:1 to UPA 15 mg once daily (QD) or PBO for 14 weeks. Pain endpoints evaluated here included the proportion of patients achieving ≥30%, ≥50%, and ≥70% reduction from baseline, minimal clinically important difference (MCID, defined as ≥1 point reduction or ≥15% reduction from baseline), and much better improvement (MBI, defined as ≥2 point reduction and ≥33% reduction from baseline) in Patient's Global Assessment (PGA) of pain, total back pain, and nocturnal back pain on a 0–10 numeric rating scale [3,4]. Non-responder imputation incorporating multiple imputation to handle missing data due to COVID-19 was used.ResultsA total of 211 patients received UPA 15 mg QD and 209 patients received PBO. Higher proportions of patients receiving UPA vs PBO achieved ≥30% and ≥50% reductions in PGA of pain, total back pain, and nocturnal back pain as early as week 2 that were sustained at all time points through 14 weeks (nominal P<0.05;Figure 1a-c). Achievement of ≥70% reductions in PGA of pain and nocturnal back pain were higher at week 4 and sustained thereafter (Figures 1a and 1c), and achievement of ≥70% reduction in total back pain was higher at week 2 and week 8, but not week 4, and sustained thereafter (Figure 1b). Results were similar for the proportion of patients achieving MCID and MBI, with improvements in PGA of pain, total back pain, and nocturnal back pain for UPA vs PBO as early as week 1 (MCID) or week 2 (MBI) that were sustained through week 14 (all nominal P<0.001;Table 1).Table 1.Achievement of MCID and MBI in Pain Outcomes at Week 14 (NRI-MI)Responder Rate (95% CI), %Pain OutcomesUPA 15 mgPBONominal P ValuePGA of painMCID81.0 (75.8–86.3)62.7 (56.1–69.2)<0.0001MBI60.7 (54.1–67.3)24.9 (19.0–30.7)<0.0001Total back painMCID80.1 (74.7–85.5)65.1 (58.6–71.5)0.0005MBI58.3 (51.6–64.9)25.4 (19.5–31.3)<0.0001Nocturnal back painMCID82.9 (77.9–88.0)61.3 (54.7–67.9)<0.0001MBI61.6 (55.0–68.2)32.1 (25.7–38.4)<0.0001MBI, much better improvement;MCID, minimal clinically important difference;NRI-MI, non-responder imputation incorporating multiple imputation to handle missing data due to COVID-19;PBO, placebo;PGA, Patient's Global Assessment;UPA, upadacitinib.ConclusionIn patients with active AS who were bDMARD-IR, greater proportions of patients treated with UPA achieved rapid and clinically meaningful reductions in pain vs PBO as early as week 2 that were sustained through 14 weeks across multiple pain assessments.References[1]van der Heijde D, et al. Ann Rheum Dis. 2022;81(11):1515-1523.[2]van der Heijde D, et al. Lancet. 2019;394(10214):2108-2117.[3]McInnes IB, et al. RMD Open. 2022;8(1):doi:10.1136/rmdopen-2021-002049.[4]Salaffi F, et al. Eur J Pain. 2004;8(4):283-291.AcknowledgementsAbbVie funded this study and participated in the study design, research, analysis, data collection, interpretation of data, reviewing, and approval of the publication. All authors had access to relevant data and participated in the drafting, review, and approval of this p blication. No honoraria or payments were made for authorship. Medical writing support was provided by M. Hovenden and J. Matsuura of ICON plc (Blue Bell, PA, USA) and was funded by AbbVie.Disclosure of InterestsXenofon Baraliakos Consultant of: Novartis, Pfizer, AbbVie, Eli Lilly, UCB Pharma, Galapagos, Janssen, Celgene, and Amgen, Grant/research support from: Novartis, Pfizer, AbbVie, Eli Lilly, UCB Pharma, Galapagos, Janssen, Celgene, and Amgen, Marina Magrey Consultant of: UCB, Novartis, Eli Lilly, Pfizer, and Janssen, Grant/research support from: Amgen, AbbVie, BMS, and UCB Pharma, Louis Bessette Speakers bureau: Amgen, BMS, Janssen, UCB, AbbVie, Pfizer, Merck, Celgene, Lilly, Novartis, Organon, and Sanofi, Grant/research support from: Amgen, BMS, Janssen, UCB, AbbVie, Pfizer, Merck, Celgene, Lilly, Novartis, Sanofi, and Gilead, Kurt de Vlam Speakers bureau: Amgen, Celgene, Eli Lilly, Galapagos, Novartis, and UCB, Consultant of: Amgen, AbbVie, Celgene, Eli Lilly, Galapagos, Novartis, and UCB, Grant/research support from: Amgen, UCB, and MSD, Tianming Gao Shareholder of: AbbVie, Employee of: AbbVie, Anna Shmagel Shareholder of: AbbVie, Employee of: AbbVie, Ralph Lippe Shareholder of: AbbVie, Employee of: AbbVie, Ana Biljan Shareholder of: AbbVie, Employee of: AbbVie, Victoria Jasion Shareholder of: AbbVie, Employee of: AbbVie, Peter C. Taylor Speakers bureau: AbbVie, Consultant of: Lilly, AbbVie, Pfizer, Galapagos, Gilead, Janssen, GlaxoSmithKline, Sanofi, Fresenius, Nordic Pharma, UCB, and Biogen, Grant/research support from: Galapagos.
ABSTRACT
Background: During the COVID-19 pandemic, Canadians with RA faced considerable uncertainty due to greater risk of infection, hospitalization, changing access to RA medications, and very limited access to in-person RA care. Further, to reduce transmission of the virus and COVID-related hospitalizations, stringent mitigation measures were implemented across the country to greatly reduce social contacts including curfews, limits on private gatherings and business closures. Little is known about the impact of the COVID-19 pandemic and associated mitigation efforts in RA. We hypothesized that women and younger adults with RA would report greater impairments in HRQL. Objectives: To compare changes in HRQL prior-to and during the COVID-19 pandemic by sex and age groups in real-world RA patients seen in routine practice settings. Methods: Data were from patients in the Canadian Early Arthritis Cohort (CATCH) who completed a study visit in the year prior to the COVID-19 pandemic (Mar 2019 through Feb 2020) and a repeat assessment during the pandemic period (Mar 2020-Jan 2022). RA disease activity was assessed using the RA Flare Questionnaire, a validated patient-reported measure of current RA disease symptoms (pain, stiffness, fatigue) and function (physical, participation). An RA-FQ score ≥ 20 was used to classify RA symptoms consistent with an RA infammatory fare. HRQL was assessed using PROMIS-29 Adult Profiles. We compared changes in mean Physical (PHS) and Mental Health (MHS) scores, and the proportion of patients with impairments in each domain (i.e., scores ≥ 55 for pain interference, fatigue, anxiety, depression, and sleep and ≤45 for physical function and participation) before and during the COVID-19 pandemic across sex and age groups (<40, 40-64, ≥65 years). Results: The 938 CATCH participants in the analytic sample with data available at both time periods had a mean (SD) age of 60 (13) and RA symptom duration of 5.8 (3.7) years;72% were women, 88% were white, and 64% reported >high school education. Most (80%) were in CDAI REM/LDA at the most recent visit prior to start of pandemic. The proportion of patients with RA-FQ ≥20 were similar at both time periods. While physical and emotional RA symptom impacts remained stable in men prior to and during the COVID-19 pandemic, women reported signifcant increases in anxiety and depression during the pandemic period. Younger RA patients <40 reported increases in depression, and older RA patients (65+) reported increases in anxiety and greater impacts on participation. Conclusion: Our results illustrate that while the proportions of patients with high infammatory disease activity were similar prior to and during the COVID-19 pandemic, we observed disproportionate impacts on HRQL by sex and age with a higher proportion of women, adults <40, and those ≥65 years of age experiencing greater impairments in several HRQL domains.
ABSTRACT
Background: A growing number of studies indicate the considerable mental health impacts of the prolonged COVID-19 pandemic in the general population as chronic stress is a risk factor for the development of depression and anxiety. Mood disorders are more prevalent in RA and a history of anxiety or depressive disorders increases the risk of recurrence in the future. Objectives: To compare trends in prevalence of anxiety and depressive symptoms, prior to and during the COVID-19 pandemic in RA patients with and without a lifetime history of mood disorders. Methods: Data were from RA patients diagnosed and treated for RA in rheumatology clinics across Canada enrolled in the Canadian Early Arthritis Cohort (CATCH) Study. We estimated monthly trends in prevalence of clinically sig-nifcant levels of anxiety and depression (PROMIS Depression and Anxiety 4a score 55+) from all visits between Mar 2019 and Jan 2022 and compared monthly trends in anxiety and depression in the year prior to (Mar 2019-Feb 2020) and during the pandemic (Mar 2020 to Jan 2022) stratifed by lifetime history of mood disorders. Results: 4,148 visits were completed from Mar 2019 to Jan 2022 in 1,644 RA patients with a mean (SD) age of 60 (14) and disease duration of 6 (4) years. 73% were women, 84% white, 60% had completed some post-secondary education, and 77% were in CDAI REM/LDA at the visit closest to the start of pandemic. 253 (15%) reported a lifetime history of depression and 217 (13%) a lifetime history of anxiety;8% reported prior treatment for either. Patients with a history of mood disorders had higher levels of depression and anxiety prior-to and during the pandemic compared with patients without a history of mood disorders (Table 1). Proportions were highest during COVID waves in all and were substantially higher and more variable in people with a previous history of mood disorders as compared to those without a history (Figure 1). While depressive symptoms peaked early in the pandemic, anxiety increased with each wave, peaking in Wave 3 (May-Jun 2021). During the frst 22 months of the COVID-19 pandemic, the proportion of patients with depression and anxiety increased in all groups. More than half of those with a history of emotional distress had clinically signifcant levels of depression and anxiety;proportions were highest during COVID waves in all and were substantially higher in people with previous history as compared to those without a history (see Figure 1). Whereas depressive symptoms peaked early in the pandemic, anxiety increased with each wave, peaking in Wave 3 (May-Jun 2021). Conclusion: Symptoms of anxiety and depression were common in Canadian adults with RA prior to and after the onset of the COVID-19 pandemic. Whereas others have found that high levels of depression and anxiety occurred early in the pandemic but declined fairly rapidly in the general population1, emotional distress was not attenuated over time in this large cohort of RA patients. Individuals reporting lifetime history of mood disorders were more than twice as likely to report anxiety and depression, with depression peaking early in the pandemic and anxiety growing with each successive wave in the frst year. The results demonstrate the importance of applying a lifetime perspective as previous episodes of anxiety and depression may be an important marker of increased vulnerability and recurrence in RA patients, particularly during the pandemic.
ABSTRACT
Background: Real-world evidence on achieving treatment targets with apremilast (APR) in patients (pts) with PsA is limited. In the phase 3 PALACE trials, pts reached remission (REM)/low disease activity (LDA) targets at 52 wks most frequently when early APR treatment was initiated and pts were in moderate disease activity, as measured by Clinical Disease Activity Index for PsA (cDAPSA) score. In APPRAISE, we assessed APR effectiveness/tolerability in pts with PsA in routine clinical practice in Canada. Objectives: This interim efficacy analysis focused on the available data on APR effectiveness measuring rate of achieving cDAPSA REM or LDA at 12 mos and Pt Acceptable Symptom Status (PASS) results. Methods: The prospective, multicenter, observational APPRAISE study assessed APR effectiveness/tolerability in adults with active PsA in routine clinical care enrolled from July 2018-March 2020. Pts were followed from treatment initiation to 12 mos, with visits suggested every 4 mos. The primary effectiveness endpoint was the rate of achieving at least LDA (cDAPSA <14) at 12 mos. Pt-reported outcome measures were assessed. Data reported are as observed in pts continuing APR treatment. Results: In total, 101 pts were enrolled in APPRAISE. Mean age was 52 yrs;56% were women. Mean (SD) PsA duration at baseline (BL) was 6 (8) yrs. Oligoarticular disease (≤4 joint involvement) was most common (41%), followed by polyarticular (35%). Most pts (92%) received prior conventional DMARDs and 17% received prior biologic therapy;concomitant MTX was reported in 41% at BL. By 12 mos, 41/101 enrolled pts discontinued, 35 reached 12 mos follow-up (4 mos: n=92;8 mos: n=61), and 25 have yet to reach 12 mos. The majority (92%) of discontinuations due to lack/loss of effectiveness or AEs occurred within 4-8 mos. AEs were primarily GI related early in treatment. The proportion of pts with continued APR achieving cDAPSA REM/LDA treatment targets increased significantly over time (Figure 1). Significant reductions were seen over 12 mos in swollen/tender joint counts and plaque psoriasis, with reduced mean (SD) body surface area of -4% (9%) (Table 1). Prevalence of dactylitis/enthesitis at BL, 4, 8, and 12 mos was 17%/33%, 9%/24%, 5%/19%, and 0%/21%, respectively. Pain assessment (VAS) significantly improved over time. The proportion of pts achieving PASS with continued APR increased significantly over 12 mos (BL: 27%;12 mos: 65%) (Figure 1). COVID restrictions impacted in-office assessment visits, necessitating reliance on virtual visits. Conclusion: Pts with PsA receiving APR were assessed at regular intervals in routine clinical care in Canada. This interim analysis revealed a greater number of pts receiving APR (66%) who completed the 12-mo follow-up achieved REM or LDA, as measured by cDAPSA over 12 mos. A majority of pts (65%) reported satisfaction with their disease state, as measured by PASS. No new safety signals were observed.