Canadian Rheumatology Association/Spondyloarthritis Research Consortium of Canada Living Treatment Recommendations for the Management of Axial Spondyloarthritis.

OBJECTIVE: To provide a set of living treatment recommendations that will provide contemporary guidance on the management of patients with axial spondyloarthritis (axSpA) in Canada. METHODS: The Spondyloarthritis Research Consortium of Canada (SPARCC), in conjunction with the Canadian Rheumatology Association, organized a treatment recommendations panel composed of rheumatologists, researchers, allied health professionals, and a patient advocate. A Grading of Recommendations Assessment, Development, and Evaluation (GRADE)-ADOLOPMENT approach was used in which existing guidelines were adopted or adapted to a Canadian context. Recommendations were also placed in a health equity framework. RESULTS: 56 recommendations were made for patients with active axSpA, stable axSpA, active or stable axSpA, comorbidities, and for assessment, screening, and imaging. Recommendations were also made for principles of management, disease monitoring, and ethical considerations. CONCLUSION: These living treatment recommendations will provide up to date guidance for the management of axSpA for Canadian practice. As part of the living model, they will be updated regularly as changes occur in the treatment landscape.

Early clinical response associates with long-term outcomes with ixekizumab in radiographic axial spondyloarthritis.

BACKGROUND: The Assessment of SpondyloArthritis international Society-European Alliance of Associations for Rheumatology recommendations for axial spondyloarthritis (axSpA) management include patient assessment for biological disease-modifying antirheumatic drug (bDMARD) treatment response after at least 12 weeks of treatment. The current treat-to-target strategy for axSpA is to achieve inactive disease (ID; Axial Spondyloarthritis Disease Activity Score (ASDAS) <1.3) or at least low disease activity (LDA; 1.3≤ASDAS<2.1).To investigate the association between treatment response at week 12 and/or week 24 and attainment of the ASDAS<2.1 treat-to-target recommendation at week 52 in bDMARD-naïve patients with radiographic (r-)axSpA treated with ixekizumab (IXE). METHODS: This post hoc analysis included patients randomly assigned to IXE 80 mg every 4 weeks from COAST-V (NCT02696785), a phase 3 trial in bDMARD-naïve patients with r-axSpA. The proportion of patients who achieved ASDAS<2.1 at week 52 was measured among those who attained or not clinically important improvement (CII, ∆ASDAS≥1.1) response, and among those with ID, LDA and high or very high disease activity at week 12 and/or week 24. Non-response was assumed for missing data. RESULTS: Amongst 81 patients, 47 (58.0%) achieved ASDAS CII at week 12, with 70.2% (n=33) achieving ASDAS<2.1 at week 52. At week 24, 52 (64.2%) patients achieved ASDAS CII, with 71.2% (n=37) achieving ASDAS<2.1 at week 52. Of the 24 patients who did not achieve ASDAS CII at either week 12 or week 24, 5 (20.8%) achieved ASDAS<2.1 at week 52. CONCLUSION: This analysis reinforces the current recommendation that continuing treatment in those achieving ASDAS CII at week 12 and/or week 24 increases the likelihood of obtaining ID/LDA at week 52. TRIAL REGISTRATION NUMBER: NCT02696785.

A Canadian Retrospective Chart Review Evaluating Concomitant Methotrexate De-escalation Patterns in Patients with Rheumatoid Arthritis Treated with Biologic or Targeted Synthetic DMARDs.

INTRODUCTION: Rheumatoid arthritis (RA) guidelines recommend methotrexate (MTX)-anchored therapy with biologic or targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs); however, tolerability issues often lead to non-adherence. Canadian data on MTX tapering and/or withdrawal following b/tsDMARD initiation are minimal. This chart review assessed frequency of MTX tapering or withdrawal following b/tsDMARD initiation and the impact on disease status in Canadian adults with RA. METHODS: Eligible patients had received MTX for ≥ 3 months before b/tsDMARD initiation. The b/tsDMARD was prescribed continuously for ≥ 18 months. Patients taking > 10 mg/day oral prednisone or equivalent were excluded. RESULTS: Eight hundred eighty-nine patients (mean baseline MTX dose 19.0 mg/week) prescribed b/tsDMARDs (tumor necrosis factor inhibitor 52.1%, Janus kinase inhibitor 18.3%, interleukin-6 inhibitor [IL-6i] 11.9%, other 17.7%) were evaluated at 22 Canadian centers. Within 2 years of b/tsDMARD initiation, MTX was tapered in 123 (13.8%) patients and discontinued in 147 (16.5%), most commonly due to planned tapering (36.6%) and patient decision (27.2%), respectively, and most commonly with IL-6i use (34.9%). The MTX dose was unchanged for 582 (65.5%) patients and increased for 37 (4.2%). Missing data limit interpretations of MTX dose effects on some secondary endpoints and challenge the assertion that a disease activity measure-based treat-to-target approach is routinely used in Canadian rheumatology practice. CONCLUSIONS: Methotrexate tapering or withdrawal occurred in 30.4% of Canadians with RA within 2 years following b/tsDMARD initiation. Baseline disease activity measures were missing from many medical records. However, for patients with baseline assessments, MTX tapering or discontinuation did not worsen disease activity.

Risk factors for prevalent and incident hypertension in rheumatoid arthritis: data from the Canadian Early Arthritis Cohort.

Objective: Hypertension (HTN) is a common comorbidity in RA. This study aimed to explore the prevalence and incidence of HTN and baseline factors associated with incident HTN in early RA (ERA). Methods: Data were from the Canadian Early Arthritis Cohort (CATCH), an inception cohort of ERA patients having <1 year of disease duration. HTN was determined by patient- or physician-reported diagnosis, the use of anti-hypertensives and/or blood pressure. Multivariable logistic regression was performed to determine baseline factors associated with prevalent and incident HTN in this population. Results: The study sample included 2052 ERA patients [mean age 55 years (s.d. 14), 71% female). The prevalence of HTN at study enrolment was 26% (23% in females and 34% in males). In both sexes, prevalent HTN was associated with older age, diabetes and hyperlipidaemia. HTN was associated with being overweight or high alcohol consumption in females. Of the RA patients who did not have HTN at enrolment, 24% (364/1518) developed HTN during the median follow-up period of 5 years (range 1-8). Baseline factors significantly associated with incident HTN were older age, being overweight, excess alcohol consumption and having hyperlipidaemia. Incident HTN was associated with high alcohol consumption in males and with hyperlipidaemia in females. RA-associated disease factors and treatments were not significantly associated with prevalent or incident HTN. Conclusions: Early RA patients had a high incidence of hypertension with the highest risk in older patients with traditional cardiovascular risk factors.

Which advanced treatment should be used following the failure of a first-line anti-TNF in patients with rheumatoid arthritis? 15 years of evidence from the Quebec registry RHUMADATA.

BACKGROUND: Since 2000, advanced therapies (AT) have revolutionized the treatment of moderate to severe rheumatoid arthritis (RA). Randomized control trials as well as observational studies together with medication availability often determine second-line choices after the failure of first Tumor Necrosis Factor inhibitors (TNFi). This led to the observation that specific sequences provide better long-term effectiveness. We investigated which alternative medication offers the best long-term sustainability following the first TNFi failure in RA. METHODS: Data were extracted from RHUMADATA from January2007. Patients were followed until treatment discontinuation, loss to follow-up, or November 25, 2022. Kaplan-Meier and Cox regression models were used to compare discontinuation between groups. Missing data were imputed, and propensity scores were computed to reduce potential attribution bias. Complete, unadjusted, and propensity score-adjusted imputed data analyses were produced. RESULTS: 611 patients (320 treated with a TNFi and 291 treated with molecules having another mechanism of action (OMA)) were included. The mean age at diagnosis was 44.5 and 43.9 years, respectively. The median retention was 2.84 and 4.48 years for TNFi and OMAs groups. Using multivariable analysis, the discontinuation rate of the OMA group was significantly lower than TNFi (adjHR: 0.65; 95% CI: 0.44-0.94). This remained true for the PS-adjusted MI Cox models. In a stratified analysis, rituximab (adjHR: 0.39; 95% CI: 0.18-0.84) had better retention than TNFi after adjusting for patient characteristics. CONCLUSION: Switching to an OMA, especially rituximab, in patients with failure to a first TNFi appears to be the best strategy as a second line of therapy.

Impact of anti-rheumatic treatment on the individual components of the ACR composite score in patients with rheumatoid arthritis: real-world data.

OBJECTIVES: Standard criteria for measuring treatment efficacy in patients with rheumatoid arthritis (RA) include American College of Rheumatology (ACR) response rates, which require meeting a threshold of ≥20/50/70% improvement in several physician- and patient-reported measures. We aimed to evaluate the impact of csDMARDs, TNF inhibitors (TNFi), and tofacitinib (TOFA) on ACR components in real-life practice. METHODS: Clinical data of RA patients with a CDAI >10 at the time they started a treatment were pooled from two registries: Ontario Best Practices Research Initiative (OBRI) and RHUMADATA. Endpoints included proportions of patients achieving: ACR20/50/70 responses, ≥20/50/70% improvements and mean percentage improvement in individual ACR components at Month 6. We also adjusted for potential confounders to compare impact of these medications on outcomes of interest. RESULTS: A total of 669 patients were included (csDMARD, n=157, TNFi, n=252; TOFA, n=260). An overall higher proportion in all three-medication groups achieved ≥20/50/70% improvement in primary ACR components vs. secondary components. Among secondary components, ≥20/50/70% improvement rates were numerically highest for PhGA and lowest for HAQ-DI and pain. Among ACR20/50/70 responders for all medications, the mean percentage improvement was more than 80% for primary components, and ranged from 30% to 80% for secondary components. A significantly lower proportion of patients in TNFi group achieved to at least 50% improvement in pain compared to TOFA after adjusting. CONCLUSIONS: In this real-world practice, physician-reported measures contribute slightly more to overall ACR20/50/70 responses. Pain was the most important factor in achieving an ACR50 TOFA users, possibly reflecting the different effects of JAKi on pain.

Long-term safety and efficacy of upadacitinib versus adalimumab in patients with rheumatoid arthritis: 5-year data from the phase 3, randomised SELECT-COMPARE study.

OBJECTIVES: To assess the safety and efficacy of upadacitinib versus adalimumab from SELECT-COMPARE over 5 years. METHODS: Patients with rheumatoid arthritis and inadequate response to methotrexate were randomised to receive upadacitinib 15 mg once daily, placebo or adalimumab 40 mg every other week, all with concomitant methotrexate. By week 26, patients with insufficient response to randomised treatment were rescued; patients remaining on placebo switched to upadacitinib. Patients completing the 48-week double-blind period could enter a long-term extension. Safety and efficacy were assessed through week 264, with radiographic progression analysed through week 192. Safety was assessed by treatment-emergent adverse events (TEAEs). Efficacy was analysed by randomised group (non-responder imputation (NRI)) or treatment sequence (as observed). RESULTS: Rates of TEAEs were generally similar with upadacitinib versus adalimumab, although numerically higher rates of herpes zoster, lymphopenia, creatine phosphokinase elevation, hepatic disorder and non-melanoma skin cancer were reported with upadacitinib. Numerically greater proportions of patients randomised to upadacitinib versus adalimumab achieved clinical responses (NRI); Clinical Disease Activity Index remission (≤2.8) and Disease Activity Score based on C reactive protein <2.6 were achieved by 24.6% vs 18.7% (nominal p=0.042) and 31.8% vs 23.2% (nominal p=0.006), respectively. Radiographic progression was numerically lower with continuous upadacitinib versus adalimumab at week 192. CONCLUSION: The safety profile of upadacitinib through 5 years was consistent with the known safety profile of upadacitinib, with no new safety risks. Clinical responses were numerically higher with upadacitinib versus adalimumab at 5 years. Upadacitinib demonstrates a favourable benefit-risk profile for long-term rheumatoid arthritis treatment. TRIAL REGISTRATION NUMBER: NCT02629159.

Having More Tender Than Swollen Joints Is Associated With Worse Patient-Reported Outcomes in Patients With Early RA.

BACKGROUND/OBJECTIVE: In patients with rheumatoid arthritis (RA), high tender-swollen joint differences (TSJDs) have been associated with worse outcomes. A better understanding of the phenotype and impact of high TSJD on patient-reported outcomes (PROs) in early RA may lead to earlier personalized treatment targeting domains that are important to patients today. Our objectives were to evaluate the impact of TSJD on updated PROs in patients with early RA over 1 year and to determine differences in associations by joint size. METHODS: This longitudinal cohort study followed patients with active, early RA enrolled in the Canadian Early Arthritis Cohort between 2016 and 2022, who completed clinical assessments and PROMIS-29 measures over 1 year. Twenty-eight joint counts were performed and TSJDs calculated. Adjusted associations between TSJD and PROMIS-29 scores were estimated using separate linear-mixed models. Separate analyses of large versus small-joint TJSDs were performed. RESULTS: Patients with early RA (n = 547; 70% female; mean [SD] age, 56 [15] years; mean [SD] symptom duration, 5.3 [2.9] months) were evaluated. A 1-point increase in TSJD was significantly associated with worse PROMIS T-scores in all domains: physical function (adjusted regression coefficient, -0.27; 95% confidence interval [CI], -0.39, -0.15), social participation (adjusted regression coefficient, -0.34; 95% CI, -0.50, -0.19), pain interference (adjusted regression coefficient, 0.49; 95% CI, 0.35, 0.64), sleep problems (adjusted regression coefficient, 0.29; 95% CI, 0.16, 0.43), fatigue (adjusted regression coefficient, 0.34; 95% CI, 0.18, 0.50), anxiety (adjusted regression coefficient, 0.23; 95% CI, 0.08, 0.38), and depression (adjusted regression coefficient, 0.20; 95% CI, 0.06, 0.35). Large-joint TSJD was associated with markedly worse PROs compared with small-joint TSJD. CONCLUSIONS: Elevated TSJD is associated with worse PROs particularly pain interference, social participation, and fatigue. Patients with more tender than swollen joints, especially large joints, may benefit from earlier, targeted therapeutic interventions.

Real-World Effectiveness of Upadacitinib for Treatment of Rheumatoid Arthritis in Canadian Patients: Interim Results from the Prospective Observational CLOSE-UP Study.

INTRODUCTION: Upadacitinib (UPA), a selective, reversible, oral Janus kinase (JAK)-1 inhibitor, was approved in 2019 in Canada for the treatment of adults with moderately to severely active rheumatoid arthritis (RA). This phase 4 prospective study aimed to characterise the effectiveness of UPA in the real-world population of patients with RA. METHODS: Adults with RA who initiated treatment with once daily UPA (15 mg) and enrolled in the Canadian Real-Life post-marketing Observational Study assessing the Effectiveness of UPadacitinib for treating rheumatoid arthritis (CLOSE-UP) and who completed a 6-month assessment as of 28 February 2023 were included. The primary endpoint of the CLOSE-UP study is the proportion of patients achieving a Disease Activity Score-28 Joint Count C-reactive protein (DAS28-CRP) < 2.6 at 6 months. Data was collected at routine visits. Data analysed and summarised descriptively for the overall interim population and for subgroups based on prior therapy included remission or low disease activity, patient-reported outcomes (PROs), and adverse events. RESULTS: A total of 392 patients were included in the interim analysis. Overall, 63.5% (191/301) of patients achieved a DAS28-CRP score < 2.6 at month 6, with similar rates observed for all subgroups analysed according to prior therapy including those with prior JAK inhibitor exposure (range 57.4-71.0%), and in patients who received UPA monotherapy (71.6% [48/67]). Early (month 3) and sustained improvements up to 6 months were observed for all PROs. The safety profile was consistent with previous reports. CONCLUSION: Real-world improvements in disease activity and PROs in response to UPA treatment were consistent with clinical trial data across a range of Canadian patients with prior therapy exposure and with UPA monotherapy, with an overall favourable benefit-risk profile. TRIAL REGISTRATION: NCT04574492.

Long-term Efficacy and Safety Following Switch Between Upadacitinib and Adalimumab in Patients with Rheumatoid Arthritis: 5-Year Data from SELECT-COMPARE.

INTRODUCTION: This study aimed to describe the long-term efficacy and safety of upadacitinib and adalimumab through 228 weeks following immediate switch to the alternate therapy with a different mechanism of action (MoA) in patients with rheumatoid arthritis (RA) not achieving treatment goals with their initial randomized therapy in the ongoing phase 3 SELECT-COMPARE study. METHODS: Patients with non-response or incomplete response to initially prescribed upadacitinib 15 mg once daily or adalimumab 40 mg every other week were switched to the alternate therapy by week 26. Efficacy was evaluated through 228 weeks post-switch using validated outcome measures, including Clinical Disease Activity Index (CDAI) low disease activity (LDA; ≤ 10)/remission (≤ 2.8); 28-joint Disease Activity Score based on C-reactive protein ≤ 3.2/< 2.6; ≥ 20%/50%/70% improvement in American College of Rheumatology (ACR) response criteria; and change from baseline in ACR core components. Data are reported as observed. Safety was assessed by treatment-emergent adverse events (TEAEs) through week 264. RESULTS: Of patients initially randomized to upadacitinib and adalimumab, 38.7% and 48.6%, respectively, switched to the alternate therapy by week 26. Clinically relevant improvements in all efficacy measures were observed through 228 weeks post-switch and were generally similar between groups, with small numeric differences mostly in favor of switching to upadacitinib. CDAI remission was achieved by 32.7% and 28.6% of initial non-responders, and 27.5% and 27.3% of incomplete responders, while CDAI LDA was achieved by 76.9% and 72.9% of non-responders, and 72.5% and 72.7% of incomplete responders switching to upadacitinib and to adalimumab, respectively. TEAE rates were similar between groups, although herpes zoster infection, lymphopenia, and creatine phosphokinase elevation were more frequent when switching to upadacitinib. No new safety signals were identified. CONCLUSION: Switching to a different MoA may provide long-term benefit to patients with RA not achieving treatment goals with their initial therapy, with acceptable safety profiles. TRIAL REGISTRATION: NCT02629159.

Having More Tender Than Swollen Joints is Associated With Worse Function and Work Impairment in Patients With Early Rheumatoid Arthritis.

OBJECTIVE: Patients with early rheumatoid arthritis (RA) may present with more tender than swollen joints, which can persist. Elevated tender-swollen joint difference (TSJD) is often challenging, because there may be multiple causes and it may contribute to overestimating disease activity. Little is known about the phenotype and impact of TSJDs on patient function. Our objective was to evaluate the impact of TSJD on functional outcomes in early RA and to see whether associations vary by joint size. METHODS: Data were from patients with active, early RA (≤12 months) enrolled in the Canadian Early Arthritis Cohort, who completed assessments of general function (Multidimensional Health Assessment Questionnaire [MDHAQ]), upper extremity (UE) function (Quality of Life in Neurological Disorders [Neuro-QoL] UE scale), and work/activity impairment (Work Productivity and Activity Impairment RA) over their first year of follow-up. A total of 28 joint counts were performed. TSJDs were calculated. Adjusted associations between TSJDs and functional outcomes were estimated in separate multivariable linear mixed effects models. Separate analyses were performed for large- versus small-joint TSJD. RESULTS: Patients (N = 547) were 70% female, mean age 56 (SD 15) years, mean disease duration 5.3 (SD 2.9) months. At baseline, 287 (52%) had TSJD >0 (43% involved large joints and 34% small joints), decreasing to 32% at 12 months. A one-point increase in TSJD was significantly associated with worse function (MDHAQ: adjusted mean change 0.10, 95% confidence interval [CI] 0.08-0.13; Neuro-QoL UE function T score: adjusted mean change -0.59, 95% CI -0.76 to -0.43; and greater work impairment: adjusted mean change 1.95%, 95% CI 0.85%-3.05%). Higher large-joint TSJDs were associated with the worst functional outcomes. CONCLUSION: Having more tender than swollen joints is common in early RA and is associated with worse function, most notably when involving large joints. Early identification and targeted intervention strategies may be needed.

Use of Apremilast to Achieve Psoriatic Arthritis Treatment Goals and Satisfaction at 1 Year in the Canadian Real-World APPRAISE Study.

INTRODUCTION: The APPRAISE study was conducted to better understand the 12-month effectiveness, tolerability, and patient satisfaction with apremilast treatment for patients with psoriatic arthritis (PsA) in real-world settings. METHODS: APPRAISE (NCT03608657), a prospective, multicenter, observational study, enrolled adults with active PsA prescribed apremilast per routine care between July 2018 and March 2020. Patients were followed for 12 months with visits suggested every 4 months. The primary outcome measure was achievement of remission (REM) or low disease activity (LDA), defined as a Clinical Disease Activity Index for Psoriatic Arthritis (cDAPSA) score ≤ 13. RESULTS: Of the 102 patients who enrolled, 45 (44.1%) discontinued the study by 12 months. Most patients (75.5%) had moderate or high disease activity, and 24.5% were in REM/LDA at baseline based on cDAPSA score. Achievement of cDAPSA REM/LDA was 63.7%, 67.2%, and 53.8% at months 4, 8, and 12, respectively. In those continuing in the study, significant improvements were seen in swollen and tender joint counts, pain visual analog scale, psoriasis body surface area, and complete dactylitis resolution. Enthesitis reduction was also observed. Improvements in treatment satisfaction and patient-reported outcomes, including Health Assessment Questionnaire-Disability Index and the 36-item Short Form physical and mental component scores, were observed over 12 months. The proportion of patients achieving a Patient-Acceptable Symptom State (PASS) increased significantly from baseline at months 4, 8, and 12 (P < 0.001). Apremilast was well tolerated; the most frequent adverse events (AEs) leading to discontinuation were diarrhea (9/102 [8.8%]), nausea (4/102 [3.9%]), and migraine (4/102 [3.9%]). CONCLUSION: In this real-world study conducted in Canadian rheumatology clinics, apremilast demonstrated clinical effectiveness in patients with active PsA, along with patient satisfaction with treatment. Safety findings were consistent with previously reported clinical data. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT03608657.

COVID-19 Vaccine in Immunosuppressed Adults with Autoimmune rheumatic Diseases (COVIAAD): safety, immunogenicity and antibody persistence at 12 months following Moderna Spikevax primary series.

OBJECTIVE: To assess the safety, immunogenicity and cellular responses following the Moderna Spikevax primary series in rheumatic disease. METHODS: We conducted a 12-month, prospective, non-randomised, open-label, comparative trial of adults with either rheumatoid arthritis (RA, n=131) on stable treatment; systemic lupus erythematosus (SLE, n=23) on mycophenolate mofetil (MMF); other rheumatic diseases on prednisone ≥10 mg/day (n=8) or age-matched/sex-matched controls (healthy control, HC, n=58). Adverse events (AEs), humoral immune responses (immunogenicity: IgG positivity for anti-SARS-CoV-2 spike protein and its receptor binding domain, neutralising antibodies (NAbs)), cellular responses (ELISpot) and COVID-19 infection rates were assessed. RESULTS: Frequency of solicited self-reported AEs following vaccination was similar across groups (HC 90%, RA 86%, SLE 90%); among them, musculoskeletal AEs were more frequent in RA (HC 48% vs RA 66% (Δ95% CI CI 3 to 32.6)). Disease activity scores did not increase postvaccination. No vaccine-related serious AEs were reported. Postvaccination immunogenicity was reduced in RA and SLE (RA 90.2%, SLE 86.4%; for both, ΔCIs compared with HC excluded the null). Similarly, NAbs were reduced among patients (RA 82.6%, SLE 81.8%). In RA, age >65 (OR 0.3, 95% CI 0.1 to 0.8) and rituximab treatment (OR 0.003, 95% CI 0.001 to 0.02) were negative predictors of immunogenicity. ELISpot was positive in 16/52 tested RA and 17/26 HC (ΔCI 11.2-53.3). During the study, 11 HC, 19 RA and 3 SLE patients self-reported COVID-infection. CONCLUSION: In COVID-19 Vaccine in Immunosuppressed Adults with Autoimmune Diseases, the Moderna Spikevax primary series was safe. MMF, RA age >65 and rituximab were associated with reduced vaccine-induced protection.

Late onset leflunomide-induced cutaneous ulcers in a seronegative arthritis patient: A case report.

The differential diagnosis for chronic cutaneous ulcers is wide. Once the common causes have been excluded, infrequent ones, including drugs, should be considered. We report the case of a 67 year old woman with multiple ulcers not responding to conventional treatment. Multiple investigations including laboratory testing, skin biopsies and tissue cultures were negative. A few cases of leflunomide-induced cutaneous ulcers are reported in the literature. Our patient was on this drug for 12 years. Discontinuation of leflunomide led to ulcers resolution. This is the longest reported time interval between leflunomide initiation and ulceration onset.

Treatment with Upadacitinib in Active Psoriatic Arthritis: Efficacy and Safety Data of the First 192 Patients from the UPJOINT Study, a Multicentre, Observational Study in Clinical Practice.

INTRODUCTION: Our aim was to investigate the efficacy and safety of upadacitinib (UPA) in patients with either oligo- or polyarticular active psoriatic arthritis (PsA) using routine clinical practice data from an observational, prospective, multicentre study. METHODS: This interim analysis contains upadacitinib efficacy and safety data from the UPJOINT study, collected from baseline to the week 24 visit with a focus on composite measures, clinical assessments and patient-reported outcomes, amongst others, including minimal disease activity (MDA), very low disease activity (VLDA), Disease Activity Index for Psoriatic Arthritis (DAPSA), Leeds Enthesitis Index (LEI), resolution of dactylitis and nail psoriasis and body surface area affected by skin psoriasis (BSA). RESULTS: A total of 296 patients with baseline data and 192 with completed week 24 visits were included in the analysis. The proportion of patients achieving MDA increased from 2.7% at baseline to 39.1% at week 24 (95% CI 32.1, 46.3). Similarly, the number of patients in DAPSA remission (DAPSA ≤ 4) increased from 0 at baseline to 32 (16.7%) by week 24. At that time, 59.4% of the patients were either in DAPSA remission or had low disease activity (DAPSA ≤ 14). During the 24 weeks time frame, the proportion of patients with BSA ≤ 3 increased from 80.7% to 91.1%. Furthermore, at weeks 12 and 24, 45.14% and 47.19% of affected patients showed a resolution of enthesitis. Active dactylitis and nail psoriasis at baseline were reported to affect 10.5% and 22.0%, decreasing to 2.6% and 5.7% at week 24, respectively. The safety findings are consistent with the known safety profile of upadacitinib in rheumatoid arthritis and PsA; no new safety risks were identified. CONCLUSION: The data from this study confirm the findings of previous randomized controlled trials suggesting UPA is an effective treatment for active PsA without any new safety signals in patients from daily clinical practice. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT04758117.

Upadacitinib is an antirheumatic medical therapy approved for treating psoriatic arthritis with insufficient response to previous conventional or biological therapies (DMARD-IR). Psoriatic arthritis is a chronic inflammatory disease affecting the joints, spine, tendons/entheses, skin, nails and other parts of the musculoskeletal system. Early diagnosis and treatment initiation are essential for patients with psoriatic arthritis given the potentially irreversible damage to joints, spine, and entheses and the considerable impact on quality of life. The results presented in this manuscript help clinicians evaluate whether the efficacy and the safety profile of upadacitinib found in previous clinical trials can be reproduced in patients seen in daily clinical practice. This analysis presents descriptive data on the real-world efficacy and safety of upadacitinib, measured by clinical and patient-reported outcomes assessed in four visits over 24 weeks. In summary, our findings confirm the results of previous clinical trials showing that upadacitinib effectively reduces symptom severity of PsA and substantially increases the proportion of patients achieving treatment goals relevant to clinical practice, such as remission or very low disease activity. In addition, safety data were consistent with previous studies of upadacitinib in rheumatoid arthritis or psoriatic arthritis; no new risks to the patients' safety were identified.

Effectiveness of a treat-to-target strategy in patients with moderate to severely active rheumatoid arthritis treated with abatacept.

BACKGROUND: To compare a treat-to-target (T2T) approach and routine care (RC) in adults with active to severely active rheumatoid arthritis (RA) initiating subcutaneous abatacept. METHODS: A 12-month cluster-randomized trial in active RA patients treated with abatacept was conducted. Physicians were randomized to RC or T2T with a primary endpoint of achieving sustained Clinical Disease Activity Index (CDAI) low disease activity (LDA) at two consecutive assessments approximately 3 months apart. Additional outcomes included Simple Disease Activity Index (SDAI), Disease Activity Score 28-CRP (DAS28-CRP), Routine Assessment of Patient Index Data 3 (RAPID3), and the Health Assessment Questionnaire-Disability Index (HAQ-DI). Time to achieve therapeutic endpoints was assessed with survival analysis. RESULTS: Among the 284 enrolled patients, 130 were in the T2T group and 154 in RC. Primary endpoint was achieved by 36.9% and 40.3% of patients in T2T and RC groups, respectively. No significant between-group differences were observed in the odds of achieving secondary outcomes, except for a higher likelihood of CDAI LDA in the T2T group vs. RC (odds ratio [95% confidence interval]: 1.33 [1.03-1.71], p = 0.0263). Compared with RC, patients in the T2T group achieved SDAI remission significantly faster (Kaplan-Meier-estimated mean [standard error]: 14.0 [0.6] vs. 19.3 [0.8] months, p = 0.0428) with a trend toward faster achievement of CDAI LDA/remission, DAS28-CRP remission, and HAQ-DI minimum clinically important difference. CONCLUSIONS: Patients managed per T2T and those under RC experienced significant improvements in RA disease activity at 12 months of abatacept treatment. T2T was associated with higher odds of CDAI LDA and a shorter time to achieving therapeutic endpoints. TRIAL REGISTRATION: Name of the registry: ClinicalTrials.gov. TRIAL REGISTRATIONS: NCT03274141 . Date of registration: September 6, 2017.

Does the Type of Failure and the Choice of the Second Biologic Influence Response and Persistence on Medication in Rheumatoid Arthritis?

BACKGROUND: The type of failure may predict response to a second biologic. We evaluated the response to a second tumor necrosis factor inhibitor (TNFi) or non-TNFi in patients failing their initial TNFi, either primarily or secondarily. METHODS: Patients with rheumatoid arthritis who were biologic-naive and had a Clinical Disease Activity Index (CDAI) >10, who started their first TNFi for ≥3 months and then switched to a second biologic, were included in the study. Secondary failure was defined as 2 consecutive low-CDAI visits and then switching to a second biologic while they had moderate/severe CDAI. Primary failure was defined if it did not meet the definition of secondary failure, or if they had at least 1 moderate/severe CDAI after 3 months on treatment. We used multivariable logistic regression comparing primary versus secondary failure for achievement of CDAI ≤10 (primary outcome) and minimal clinically important differences (secondary outcome) at 6 months after switch. RESULTS: Of the 462 patients included, 64.3% and 35.7% stopped the first TNFi because of a primary and secondary failure, respectively. Patients with primary failure had a more severe disease (CDAI mean, 26.39 vs. 21.61; p < 0.001). The likelihood of achieving CDAI ≤10 (odds ratio, 4.367; 95% confidence interval, 2.428-7.856) and minimal clinically important difference (odds ratio, 2.851; 95% confidence interval, 1.619-5.020) was significantly higher for secondary than primary failure regardless of choice of a second agent. CONCLUSION: Patients with rheumatoid arthritis with secondary failure to a first TNFi responded better to a second biologic agent, regardless of the choice of biologic.

Real-World Incidence and Determinants of Infection in Patients With Rheumatoid Arthritis Treated With Golimumab After a Median Follow-Up Time of 27 Months.

OBJECTIVE: To characterize the long-term incidence of infection in patients with rheumatoid arthritis (RA) treated with subcutaneous golimumab (GOL) in Canadian routine care, assess the effect of infections on GOL retention, and explore factors associated with infection incidence. METHODS: Patients with RA enrolled in the Biologic Treatment Registry Across Canada (BioTRAC) initiating GOL treatment were included. The incidence density rates (IDRs) of total infection (TI), serious infection (SI), and nonserious infection (NSI) were calculated for the overall follow-up (90 months) and by 6-month intervals. Determinants of infection over time or within the first 6 months were explored using generalized estimating equation models and logistic regression, respectively. RESULTS: Five hundred thirty patients were included; mean baseline age was 57.7 years and RA duration was 8.0 years. Over an average follow-up of 27.0 months, the IDR for TIs was 35.1 events per 100 person-years (PYs), the majority occurring during the first 6 months; IDRs for NSIs and SIs were 32.9 and 2.2 events per 100 PYs, respectively. No predictors were identified for infection incidence within 6 months. Comorbid pulmonary disease was associated with significantly higher odds of TIs and NSIs over time, whereas higher age and high corticosteroid (CS) dose (> 5 mg/day) predicted higher odds of SIs. Incidence of SIs, but not NSIs, was associated with significantly higher odds of GOL discontinuation. CONCLUSION: Long-term GOL treatment was associated with relatively low infection rates, most being nonserious and occurring during the first 6 months. Pulmonary disease, higher age, and high CS dose were identified as significant predictors of infections. SIs, but not NSIs, predicted higher odds of GOL discontinuation. (ClinicalTrials.gov: NCT00741793).

Sustained low functional impairment in axial spondyloarthritis (axSpA): which are the primary outcomes that should be targeted to achieve this?

OBJECTIVES: To (i) determine whether sustained disease activity states, as measured by Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Ankylosing Spondylitis Disease Activity Score (ASDAS), impact function, and (ii) evaluate characteristics predicting sustained low functional impairment in a prospective axial spondyloarthritis (axSpA) cohort. METHODS: Biologic Treatment Registry Across Canada (BioTRAC) was a multi-center, prospective registry that collected real-world data on axSpA patients receiving infliximab or golimumab between 2006 and 2017. Generalized estimating equations (GEE) were used to test baseline characteristics, treatment, and duration (at 6 and 12 months vs. only at 6 or 12 months vs. neither) of low BASDAI (< 3), ASDAS-inactive disease (ID)(< 1.3), and ASDAS-low disease activity (LDA) in predicting sustained low Bath Ankylosing Spondylitis Functional Index (BASFI)(< 3) between 12 and 18 months. The adjusted impact of achieving low disease state at 6 and/or 12 months on BASFI at 18 months was analyzed by generalized linear models. RESULTS: Eight hundred ten patients were enrolled. 33.7%, 13.4%, and 24.7% achieved sustained low BASDAI, ASDAS-ID, and ASDAS-LDA, respectively. In univariable GEE of baseline variables, age and baseline BASDAI, BASFI, and ASDAS significantly predicted sustained low BASFI. In multivariable GEE, sustained low BASDAI (p < 0.001), low BASDAI only at 6 or 12 months (p = 0.001), and baseline BASFI (p < 0.001) were the only predictors of sustained low BASFI. Sustained ASDAS-ID (p = 0.040) and ASDAS-LDA (p < 0.001) were also predictors when forced into the model. Similar results were obtained when evaluating the BASFI score at 18 months. CONCLUSION: Sustained BASDAI < 3 may be a valid and feasible target for a treat-to-target strategy in axSpA having function as treatment goal.