Appropriate pain measurement relies on the use of valid, reliable tools. The aim of this study was to determine and compare the psychometric properties of 3 self-reported pain scales commonly used in the pediatric emergency department (ED). The inclusion criteria were children aged 6 to 17 years presenting to the ED with a musculoskeletal injury and self-reported pain scores ≥30 mm on the mechanical Visual Analogue Scale (VAS). Self-reported pain intensity was assessed using the mechanical VAS, Faces Pain Scale-Revised (FPS-R), and Colour Analogue Scale (CAS). Convergent validity was assessed by Pearson correlations and the Bland-Altman method; responsiveness to change was assessed using paired sample t tests and standardized mean responses; and reliability was estimated using relative and absolute indices. A total of 456 participants were included, with a mean age of 11.9 years ± 2.7 and a majority were boys (252/456, 55.3%). Correlations between each pair of scales were 0.78 (VAS/FPS-R), 0.92 (VAS/CAS), and 0.79 (CAS/FPS-R). Limits of agreement (95% confidence interval) were -3.77 to 2.33 (VAS/FPS-R), -1.74 to 1.75 (VAS/CAS), and -2.21 to 3.62 (CAS/FPS-R). Responsiveness to change was demonstrated by significant differences in mean pain scores among the scales (P < 0.0001). Intraclass correlation coefficient and coefficient of repeatability estimates suggested acceptable reliability for the 3 scales at, respectively, 0.79 and ±2.29 (VAS), 0.82 and ±2.07 (CAS), and 0.76 and ±2.82 (FPS-R). The scales demonstrated good psychometric properties for children with acute pain in the ED. The VAS and CAS showed a strong convergent validity, whereas FPS-R was not in agreement with the other scales.
Rheumatoid arthritis (RA) associated autoantibodies including anti-cyclic citrullinated peptide antibodies (ACPA) and rheumatoid factor (RF) may be present years before clinical presentation. The pre-clinical phase of RA may also be associated with subtle CRP elevations.
Objectives
The study aimed to test whether CRP levels and positive ACPA autoantibodies in pre-clinical disease may be associated with small joint imaging demonstrable synovitis.
Methods
21 patients identified from primary care and rheumatology clinics who were ACPA positive with musculoskeletal symptoms but without clinical synovitis, underwent 3T MRI scans of joints that were clinically uninvolved, but where early RA typically presents, namely the wrist, hand and forefeet. Pre- and post-contrast sequences images were scored blindly by 2 musculoskeletal radiologists for synovitis, bone oedema and erosions.
Results
91% (19/21) patients were female, median age was 51 years and median duration of early morning stiffness (EMS) 12.5 min (range 0 to 240 min). All were ACPA+ and 57% (12/21) were RF+. Median ESR at study entry was 14.5 mm/h (range 1-40 mm/h) and median CRP using a high sensitivity CRP (hs-CRP) test was 2.7 mg/L (range <0.01 to 29 mg/L). CRP levels for 14/21 (66.7%) patients fell within the normal range (<10mg/L) and x-ray erosions were not evident. All 21 cases had MRI determined synovitis. Synovitis was most frequently detected in the wrist (90.5% (19/21)). MCP synovitis was reported in 52.4% (11/21) and involvement of one or both forefeet in 66.7% (14/21). MRI determined bone oedema was evident in 52.4% (11/21) cases with 23.8% (5/21) documented in the wrists, 14.3% (3/21) in the MCPs and 33.3% (7/21) in the forefeet. MRI evident erosive change was noted in 13/21 (61.9%) of patients on MRI – 28.6% (6/21) in the wrists, 14.3% (3/21) in the MCPs and 42.9% (9/21) in the forefeet. Similar proportions of MRI changes were documented in patients who had (1) elevated CRP levels (>10mg/L) and (2) normal CRP levels (<10mg/L), including the subgroup with (3) low CRP levels detected only using a high sensitivity test (hs-CRP 0.1-5 mg/L). Synovitis was documented in each of the 3 subgroups in 7/7 (100%), 14/14 (100%) and 11/11 (100%) patients, bone oedema in 3/7 (42.9%), 8/14 (57.1%) and 5/11 (45.5%) patients and erosions in 5/7 (71.4%), 8/14 (57.1%) and 6/11 (64.5%) patients respectively.
Conclusions
This MRI imaging study of small joints in ACPA positive patients who do not have clinical evidence of joint inflammation showed that patients already have MRI determined small joint synovitis, irrespective of CRP levels. In these patients, musculoskeletal symptoms may be an early indicator of the presence of clinical synovitis. The study is ongoing to determine the specificity of these findings.
The order of use of biologic agents is still a question of debate. Phase III trial data in MTX-IR patients show very similar results across all biologic agents. No head to head study have yet been published. Prospective registries offer a unique opportunity to observe the effectiveness of these agents in a clinical setting.
Objectives
To evaluate if patients with rheumatoid arthritis (RA) treated with abatacept after failure to either a first line agent (MTX-IR) or a second line anti-TNF agents (TNF-IR) have a different drug survival rate compare to adalimumab or etanercept similarly prescribed in Rhumadata database. A secondary objective is to explore the role of MTX coprescription.
Methods
Data from patients with RA fulfilling the the ACR criteria and/or according to a rheumatologist diagnosis were extracted from the database from the 1st of January 2007. Two cohorts were extracted. The first cohort consists of patients that had failed MTX and had started either adalimumab (ADA), Etanercept (ETA) or Abatacept (ABA). Subjects in the second RA cohort had failed a first anti-TNF agent and had started an alternative treatment with either ADA, ETA or ABA. RHUMADATA® is a clinical database/software used in daily clinical practice at the IRM.
Results
290 patients were extracted. 203 were included in the first cohort and 87 composed the second cohort. Baseline demographics for both cohorts included age, disease duration, HAQ, fatigue and pain evaluation, TJC, SWC, DAS 28 ESR and SDAI. No significant differences in baseline variables were observed between treatment groups (GLM). Statistical analysis was performed using SAS version 9.3. The 5 year retention rate of abatacept, adalimumab and etanercept post MTX failure are respectively 63%, 54% and 50% without significant statistical differences (Wilcoxon p=0.6779). In that cohort, patients taking MTX with their biologic agent (ABA, ADA or ETA) demonstrated a better drug survival rate than those taking monotherapy (60% vs 32%, Wicoxon p=0.0079). All biologics combined to DMARDS exibited similar survival profiles (ETA 62%, ABA 58%, ADA 50% at 5 years, Wilcoxon p=0.4681). However, patients having failed a first anti-TNF agent showed a better drug survival rate if treated with ABA compared to ADA or ETA. Respective retention rates at 5 years are: ABA 48%, ADA and ETA 31% (Wilcoxon p=0.0381).
Conclusions
Abatacept, adalimumab and etanercept after MTX failure show similar 5-years retention rates. Combination with methotrexate improved the biologic agents survival rate at 5 years. Prescribing abatacept after a previous TNF agent failure seems to offer a more favorable alternative. References: Sequential use of biologic therapy in RA. Buch MH. Curr Opin Rheumatol 2010 May;22(3): 321-9Switching TNF-Alpha antagonists in RA: the experience of the Lorhen registry. Caporali R & al. Autoimmune Rev. 2010 Apr;9(6): 465-9Treatment options in patients with RA failing initial TNF inhibitor therapy: a critical review. Rubbert-Roth A, Finckh A. Arthritis Res Ther. 2009;11 Suppl 1:S1
Acknowledgements
The Rhumadata registry is supported by unrestricted grant from Abbott Canada, Amgen Canada, BMS Canada, Pfizer Canada, Roche Canada, UCB Canada Disclosure of Interest: None Declared
Since 2000, advanced therapies (AT) have revolutionized rheumatoid arthritis (RA) treatment. Initially, TNF-targeted therapies were the only options. Then, therapies with different modes of action (OMA) appeared. Habits and medication availability often determine second-line AT choices. Research suggests that specific sequences provide better long-term effectiveness [1,2].
Objectives
Evaluate which alternative medication provides the best sustainability following first-line TNF failure.
Methods
Data from AT prescribed since January 2007 was extracted from RHUMADATA™. Patients were followed until treatment discontinuation, loss to follow-up, or November 25, 2022. A descriptive statistic was used to compare patient characteristics. Kaplan-Meier was used to compare treatment discontinuation rates.
Results
A total of 611 patients (320 TNFi and 291 1237 OMA were included. The mean age at diagnosis was 44.5 (14.4) and 43.9 (14.8) in the TNFi and OMA groups, and disease duration at treatment initiation (TI) was 14.1 (11.1) and 12.9 (12.9). Women made up 72.8% and 81.1% of these groups. The age-adjusted Charlson Comorbidity index (ACCI) was 2.15 (1.7) and 2.1 (1.7). Patients reported more comorbidities, pain and fatigue, longer duration of morning stiffness, and higher HAQ score and disease activity in the OMA group (Table 1). The physician's global assessment of disease activity and the number of swollen and tender joints were also higher in the OMA group. OMAs retention was higher (Figure 1, logrank=0.0134) than TNFi retention following initial TNFi-IR. In a stratified analysis, rituximab (adjusted (Sidak) logrank=0.0048) had higher retention.
Conclusion
When a first TNFi fails, switching to an OMA, especially rituximab, appears to be the best strategy. Adequate assessment of more recent agents require longer observation periods.
References
[1]Choquette, D., Bessette, L., Alemao, E. et al. Arthritis Res Ther21, 138 (2019). [2]Lopatina E, Marshall DA, Coupal L, Le Lorier J, Choquette D. Curr Med Res Opin. 2021 Jan;37(1):157-166.
Acknowledgements:
NIL.
Disclosure of Interests
Denis Choquette Speakers bureau: Abbvie, Amgen, Eli Lilly, Fresenius Kabi, Novartis, Pfizer, Sandoz, Tevepharm, Consultant of: Abbvie, Amgen, Eli Lilly, Fresenius Kabi, Novartis, Pfizer, Sandoz, Tevepharm, Grant/research support from: Abbvie, Amgen, Eli Lilly, Fresenius Kabi, Novartis, Pfizer, Sandoz, Tevepharm, Louis Bessette Speakers bureau: Abbvie, Amgen, BMS, Eli Lilly, Fresenius Kabi, Janssen, Novartis, Pfizer, Sandoz, Tevepharm, UCB, Consultant of: Abbvie, Amgen, BMS, Celgene, Eli Lilly, Fresenius Kabi, Janssen, Novartis, Pfizer, Sandoz, Sanofi-Genzyme, Tevepharm, UCB, Grant/research support from: Abbvie, Amgen, BMS, Celgene, Eli Lilly, Janssen, Novartis, Pfizer, Roche, Sandoz, Sanofi-Genzyme, UCB, Loïc Choquette Sauvageau: None declared, Jacques Brown Speakers bureau: Amgen, Janssen, Consultant of: Amgen, Gilead, Paladin, Pfizer, Ultragenyx, Isabelle Ferdinand Speakers bureau: Pfizer, Consultant of: Abbvie, Eli Lilly, Fresenius Kabi, Janssen, Novartis, Pfizer, UCB, Paul Haraoui Speakers bureau: Pfizer, Consultant of: Abbvie, Amgen, Lilly, Pfizer, Sandoz, UCB, Grant/research support from: Abbvie, Amgen, Pfizer, UCB, Maxine Joly-Chevrier: None declared, Ariel Masetto Speakers bureau: Abbvie, Janssen, Novartis, Pfizer, Consultant of: Abbvie, Janssen, Novartis, Pfizer, Sanofi-Genzyme, UCB, Grant/research support from: Novartis, Frédéric Massicotte Speakers bureau: Jansen, Consultant of: Abbvie, Eli Lilly, Janssen, Pfizer, Valerie Nadon Consultant of: Abbvie, Eli Lilly, Janssen, Pfizer, Roche, Sanofi-Genzyme, Jean-Pierre Pelletier Shareholder of: ArthroLab Inc., Consultant of: TRB Chemedica SA, Grant/research support from: TRB Chemedica SA, Jean-Pierre Raynauld Speakers bureau: Abbvie, Amgen, BMS, Eli Lilly, Janssen, Novartis, Pfizer, Sandoz, Sanofi-Genzyme, Consultant of: Abbvie, ArthroLab Inc., Janssen, Pfizer, Sanofi-Genzyme, Diane Sauvageau: None declared, Angèle Turcotte: None declared, Édith Villeneuve Speakers bureau: Abbvie, BMS, Novartis, Pfizer, Consultant of: Abbvie, Amgen, Novartis, Pfizer, Louis Coupal: None declared.
To compare the efficacy of etanercept (ETN) and methotrexate (MTX) versus MTX monotherapy for remission induction in patients with early inflammatory arthritis.In a 78-week multicentre randomised placebo-controlled superiority trial, 110 DMARD-naïve patients with early clinical synovitis (≥1 tender and swollen joint, and within 3 months of diagnosis) and either rheumatoid factor, anticitrullinated protein antibodies or shared epitope positive were randomised 1:1 to receive MTX+ETN or MTX+placebo (PBO) for 52 weeks. Injections (ETN or PBO) were stopped in all patients at week 52. In those with no tender or swollen joints (NTSJ) for >26 weeks, injections were stopped early. If patients had NTSJ >12 weeks after stopping the injections, MTX was weaned. The primary endpoint was NTSJ at week 52.No statistically significant difference was seen for the primary endpoint (NTSJ at week 52 (32.5% vs 28.1% [adjusted OR 1.32 (0.56 to 3.09), p=0.522]) in the MTX+ETN and MTX+PBO groups, respectively). The secondary endpoints did not differ between groups at week 52 or 78. Exploratory analyses showed a higher proportions of patients with DAS28-CRP<2.6 in the MTX+ETN group at week 2 (38.5% vs 9.2%, adjusted OR 8.87 (2.53 to 31.17), p=0.001) and week 12 (65.1% vs 43.8%, adjusted OR 2.49 (1.12 to 5.54), p=0.026).In this group of patients with early inflammatory arthritis, almost a third had no tender, swollen joints after 1 year. MTX+ETN was not superior to MTX monotherapy in achieving this outcome. Clinical responses, however, including DAS28-CRP<2.6, were achieved earlier with MTX+ETN combination therapy.The EMPIRE trial is registered on the following trial registries: Eudract-2005-005467-29; ISRCTN 55428162 (http://www.controlled-trials.com/ISRCTN55428162/EMPIRE). The full trial protocol can be obtained from the corresponding author.
Background: Since the introduction of biologic agents around the turn of the century, the scientific evidence shows that the majority of agents, independent of the therapeutic target, have a better outcome when used in combination with methotrexate (MTX). In 2014, tofacitinib (TOFA), an agent targeting Janus kinase 1 and 3, has reached the Canadian market with data showing that the combination with MTX may not be necessary [1,2]. Objectives: To evaluate the efficacy and retention rate of TOFA in real-world patients with rheumatoid arthritis (RA). Methods: Two cohorts of patients prescribed TOFA was created. The first cohort was formed of patients who were receiving MTX concomitantly with TOFA (COMBO) and the other of patients using TOFA in monotherapy (MONO). MONO patients either never use MTX or were prescribed MTX post-TOFA initiation for at most 20% of the time they were on TOFA. COMBO patients received MTX at the time of TOFA initiation or were prescribed MTX post-TOFA initiation for at least 80% of the time. For all those patients, baseline demographic data definitions. Disease activity score and HAQ-DI were compared from the initiation of TOFA to the last visit. Time to medication discontinuation was extracted, and survival was estimated using Kaplan-Meier calculation for MONO and COMBO cohorts. Results: Overall, 194 patients were selected. Most were women (83%) on average younger than the men (men: 62.6 ± 11.0 years vs. women: 56.9 ± 12.1 years, p-value=0.0130). The patient’s assessments of global disease activity, pain and fatigue were respectively 5.0 ± 2.7, 5.2 ± 2.9, 5.1 ± 3.1 in the COMBO group and 6.2 ± 2.5, 6.5 ± 2.6, 6.3 ± 2.8 in the MONO group all differences being significant across groups. HAQ-DI at treatment initiation was 1.3 ± 0.7 and 1.5 ± 0.7 in the COMBO and MONO groups, respectively, p-value=0.0858. Similarly, the SDAI score at treatment initiation was 23.9 ± 9.4 and 25.2 ± 11.5, p-value=0.5546. Average changes in SDAI were -13.4 ± 15.5 (COMBO) and -8.9 ± 13.5 (MONO), p-value=0.1515, and changes in HAQ -0.21 ± 0.63 and -0.26 ± 0.74, p-value 0.6112. At treatment initiation, DAS28(4)ESR were 4.4 ± 1.4 (COMBO) and 4.6 ± 1.3 (MONO), p-value 0.5815, with respective average changes of -1.06 ± 2.07 and -0.70 ± 1.96, p-value=0.2852. The Kaplan-Meier analysis demonstrated that the COMBO and MONO retention curves were not statistically different (log-rank p-value=0.9318). Conclusion: Sustainability of TOFA in MONO or COMBO are not statistically different as are the changes in DAS28(4)ESR and SDAI. Despite this result, some patients may still benefit from combination with MTX. References: [1]Product Monograph - XELJANZ ® (tofacitinib) tablets for oral administration Initial U.S. Approval: 2012. [2] Reed GW, Gerber RA, Shan Y, et al. Real-World Comparative Effectiveness of Tofacitinib and Tumor Necrosis Factor Inhibitors as Monotherapy and Combination Therapy for Treatment of Rheumatoid Arthritis [published online ahead of print, 2019 Nov 9]. Rheumatol Ther . 2019;6(4):573–586. doi:10.1007/s40744-019-00177-4. Disclosure of Interests: Denis Choquette Grant/research support from: Rhumadata is supported by grants from Pfizer, Amgen, Abbvie, Gylead, BMS, Novartis, Sandoz, eli Lilly,, Consultant of: Pfizer, Amgen, Abbvie, Gylead, BMS, Novartis, Sandoz, eli Lilly,, Speakers bureau: Pfizer, Amgen, Abbvie, Gylead, BMS, Novartis, Sandoz, eli Lilly,, Louis Bessette Grant/research support from: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Merck, Novartis, Pfizer, Roche, Sanofi, UCB Pharma, Consultant of: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Merck, Novartis, Pfizer, Roche, Sanofi, UCB Pharma, Speakers bureau: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Merck, Novartis, Pfizer, Sanofi, Loïc Choquette Sauvageau: None declared, Isabelle Ferdinand Consultant of: Pfizer, Abbvie, Amgen, Novartis, Speakers bureau: Pfizer, Amgen, Boulos Haraoui Grant/research support from: Abbvie, Amgen, Pfizer, UCB, Grant/research support from: AbbVie, Amgen, BMS, Janssen, Pfizer, Roche, and UCB, Consultant of: Abbvie, Amgen, Lilly, Pfizer, Sandoz, UCB, Consultant of: AbbVie, Amgen, BMS, Celgene, Eli Lilly, Janssen, Merck, Pfizer, Roche, and UCB, Speakers bureau: Pfizer, Speakers bureau: Amgen, BMS, Janssen, Pfizer, and UCB, Frédéric Massicotte Consultant of: Abbvie, Janssen, Lilly, Pfizer, Speakers bureau: Janssen, Jean-Pierre Pelletier Shareholder of: ArthroLab Inc., Grant/research support from: TRB Chemedica, Speakers bureau: TRB Chemedica and Mylan, Jean-Pierre Raynauld Consultant of: ArthroLab Inc., Marie-Anaïs Rémillard Consultant of: Abbvie, Amgen, Eli Lilly, Novartis, Pfizer, Sandoz, Paid instructor for: Abbvie, Amgen, Eli Lilly, Novartis, Pfizer, Sandoz, Speakers bureau: Abbvie, Amgen, Eli Lilly, Novartis, Pfizer, Sandoz, Diane Sauvageau: None declared, Édith Villeneuve Consultant of: Abbvie, Amgen, BMS, Celgene, Pfizer, Roche, Sanofi-Genzyme, UCB, Paid instructor for: Abbvie, Speakers bureau: AbbVie, BMS, Pfizer, Roche, Louis Coupal: None declared
