Jaclyn Anderson

Rheumatoid Arthritis Disease Activity Measures: American College of Rheumatology Recommendations for Use in Clinical Practice

Although the systematic measurement of disease activity facilitates clinical decision making in rheumatoid arthritis (RA), no recommendations currently exist on which measures should be applied in clinical practice in the US. The American College of Rheumatology (ACR) convened a Working Group (WG) to comprehensively evaluate the validity, feasibility, and acceptability of available RA disease activity measures and derive recommendations for their use in clinical practice.

Comparison of statistically derived ASAS improvement criteria for ankylosing spondylitis with clinically relevant improvement according to an expert panel

Objective: To investigate whether the recently developed (statistically derived) “ASsessment in Ankylosing Spondylitis Working Group” improvement criteria (ASAS-IC) for ankylosing spondylitis (AS) reflect clinically relevant improvement according to the opinion of an expert panel. Methods: The ASAS-IC consist of four domains: physical function, spinal pain, patient global assessment, and inflammation. Scores on these four domains of 55 patients with AS, who had participated in a non-steroidal anti-inflammatory drug efficacy trial, were presented to an international expert panel (consisting of patients with AS and members of the ASAS Working Group) in a three round Delphi exercise. The number of (non-)responders according to the ASAS-IC was compared with the final consensus of the experts. The most important domains in the opinion of the experts were identified, and also selected with discriminant analysis. A number of provisional criteria sets that best represented the consensus of the experts were defined. Using other datasets, these clinically derived criteria sets as well as the statistically derived ASAS-IC were then tested for discriminative properties and for agreement with the end of trial efficacy by patient and doctor. Results: Forty experts completed the three Delphi rounds. The experts considered twice as many patients to be responders than the ASAS-IC (42 v 21). Overall agreement between experts and ASAS-IC was 62%. Spinal pain was considered the most important domain by most experts and was also selected as such by discriminant analysis. Provisional criteria sets with an agreement of ⩾80% compared with the consensus of the experts showed high placebo response rates (27–42%), in contrast with the ASAS-IC with a predefined placebo response rate of 25%. All criteria sets and the ASAS-IC discriminated well between active and placebo treatment (χ2=36–45; p<0.001). Compared with the end of trial efficacy assessment, the provisional criteria sets showed an agreement of 71–82%, sensitivity of 67–83%, and specificity of 81–88%. The ASAS-IC showed an agreement of 70%, sensitivity of 62%, and specificity of 89%. Conclusion: The ASAS-IC are strict in defining response, are highly specific, and consequently show lower sensitivity than the clinically derived criteria sets. However, those patients who are considered as responders by applying the ASAS-IC are acknowledged as such by the expert panel as well as by patients’ and doctors’ judgments, and are therefore likely to be true responders.

The Veterans Affairs Shift Change Physician-to-Physician Handoff Project

BACKGROUND Few studies on the safety or efficacy of current patient handoff systems exist, and few standardized electronic medical record (EMR)-based handoff tools are available. An EMR handoff tool was designed to provide a standardized approach to handoff communications and improve on previous handoff methods. METHODS In Phase I, existing handoff methods were analyzed through abstraction of printed handoff sheets and questionnaires of internal medicine residents at Department of Veterans Affairs medical centers (VAMCs). In Phase II, the handoff tool was designed, and the software was tested and revised through user feedback and regular conference calls. Phase III involved postimplementation systematic abstraction of printed handoff sheets and questionnaires of internal medicine residents. Two VAMCs participated in abstraction of printed handoff sheets, with four VAMCs responding to the questionnaires. RESULTS Handoffs were abstracted for 550 patients at baseline and 413 postimplementation. Improvements were found in consistency of information transfer for all handoff content, including code status, floor location, room number, two types of identifying information, typed format, medication, and allergy lists (p = .01). The 63 and 51 questionnaires completed pre- and postimplementation, respectively, showed improvement in perceptions of ease of use, efficiency, and readability (p < .05) and in perceptions of patient safety and quality (p < .01) without causing omission (p < .01) or commission of information (p = .02). DISCUSSION This standardized EMR-based handoff software improved data accuracy and content consistency, was well-received by users, and improved perceptions of handoff-related patient safety, quality, and efficiency. A final version of the software was incorporated into the national EMR software program and made available to all VAMCs.

Efficacy and safety of adalimumab in Chinese adults with active ankylosing spondylitis: results of a randomised, controlled trial

Background and objectives Efficacy of adalimumab for ankylosing spondylitis (AS) has been established for Western populations but not in the Chinese population. This study is the first to evaluate the efficacy and safety of adalimumab in Chinese patients with AS. Methods Chinese adults with active AS who had an inadequate response or were intolerant to ≥1 non-steroidal anti-inflammatory drugs were randomised to adalimumab 40 mg (N=229) or matching placebo (N=115) subcutaneously every other week (EOW) for 12 weeks, followed by a 12-week open-label adalimumab 40 mg EOW phase. The primary efficacy endpoint was the percentage of patients meeting the Assessment in Spondyloarthritis International Society (ASAS20) response criteria at week 12. The recently developed AS Disease Activity Score (ASDAS), as well as efficacy measures of spinal mobility, disease activity, physical function and quality of life were evaluated. Results At week 12, adalimumab treatment resulted in a significantly greater percentage of ASAS20 responders than placebo (67.2% versus 30.4%, respectively; p<0.001). Differences in ASAS20 were observed as early as week 2 (42.8% vs 6.1%, respectively; p<0.001). The percentages of patients achieving ASAS40, ASAS 5/6 and ASDAS inactive disease were significantly greater with adalimumab than placebo at week 12 (all p<0.001). Tuberculosis was reported in one patient. No cases of malignancy, lymphoma, demyelinating disease or lupus-like syndrome were reported during the study. Conclusions Adalimumab significantly reduced the signs and symptoms, improved physical function and quality of life of Chinese patients with active AS, and was generally safe and well tolerated in this population.

A Randomized, Double-Blind, Placebo-Controlled Multicenter Study of Adalimumab in Pediatric Patients With Enthesitis-Related Arthritis.

Enthesitis‐related arthritis (ERA) is a juvenile idiopathic arthritis (JIA) category, primarily affecting entheses and peripheral joints. This study evaluated efficacy, safety, and pharmacokinetics of adalimumab versus placebo in patients with ERA.

Converting modified health assessment questionnaire (HAQ), multidimensional HAQ, and HAQII scores into original HAQ scores using models developed with a large cohort of rheumatoid arthritis patients

The Stanford Health Assessment Questionnaire Disability Index (HAQ) is the gold standard functional status questionnaire in rheumatology, but it is lengthy. Three shorter versions, the modified HAQ (MHAQ), the Multidimensional HAQ (MDHAQ), and the HAQII are often used in outcomes research as HAQ substitutes. We developed conversion formulas between these modified versions and the original HAQ.

Non-radiographic axial spondyloarthritis patients without initial evidence of inflammation may develop objective inflammation over time

Abstract Objectives. In patients with active axial spondyloarthritis (axSpA), inflammation in the SIJ or spine on MRI, an elevated CRP level or both are considered useful objective assessments for disease activity and initiation of TNF antagonists. The aim of this post hoc analysis of the randomized, double-blind ABILITY-1 study (NCT00939003) was to assess changes in objective inflammation over time. Methods. Patients with non-radiographic axSpA (nr-axSpA) were randomized to receive adalimumab 40 mg every other week or placebo for 12 weeks in ABILITY-1. MRIs were performed at baseline and week 12; CRP was measured every 4 weeks. Results. Of 94 placebo-treated ABILITY-1 patients, 29 (30.9%) had a normal MRI of the SIJs and spine, 57 (60.6%) had normal CRP and 20 (21.3%) had a normal MRI of the SIJs and spine and a normal CRP at baseline. After 12 weeks of placebo, 9/29 (31.0%) patients subsequently developed inflammation on MRI, 14/57 (24.6%) patients developed elevated CRP and 10/20 (50.0%) patients developed a positive MRI and/or elevated CRP through week 12. Conclusions. Patients who have clinically active disease but who lack objective evidence of inflammation initially may benefit from subsequent retesting for inflammation to guide treatment.

Efficacy and safety of continuing versus withdrawing adalimumab therapy in maintaining remission in patients with non-radiographic axial spondyloarthritis (ABILITY-3): a multicentre, randomised, double-blind study

BACKGROUND Success of treatment withdrawal in patients with non-radiographic axial spondyloarthritis who are in remission remains unknown. The ABILITY-3 study explored the ability to withdraw adalimumab treatment in patients with non-radiographic axial spondyloarthritis who achieved sustained clinical remission after open-label treatment with adalimumab. METHODS ABILITY-3 was a multicentre, two-period study done in 107 sites in 20 countries. We enrolled adult patients (≥18 years) diagnosed with non-radiographic axial spondyloarthritis, fulfilling Assessment of SpondyloArthritis international Society classification criteria but not the modified New York radiologic criterion, who had objective evidence of active inflammation, active disease, and inadequate response to at least two non-steroidal anti-inflammatory drugs. Patients who achieved Ankylosing Spondylitis Disease Activity Score (ASDAS) inactive disease (<1·3) with open-label adalimumab (40 mg subcutaneously every other week for 28 weeks) at weeks 16, 20, 24, and 28 were randomly assigned (1:1) using an interactive voice or web response system to 40-week, double-blind treatment with adalimumab (continuation) or placebo (withdrawal). The primary efficacy endpoint was the proportion of patients who did not experience a flare (defined as ASDAS ≥2·1 at two consecutive visits) during the double-blind period. Patients who flared were rescued with open-label adalimumab. This study is registered with ClinicalTrials.gov, number NCT01808118. FINDINGS Between June 27, 2013, and October 22, 2015, 673 patients were enrolled to the study. The trial completed on April 14, 2017. Of 673 enrolled patients, 305 (45%) achieved sustained remission and were randomly assigned to double-blind treatment (152 patients to adalimumab and 153 to placebo). A greater proportion of patients continuing adalimumab than those receiving placebo did not experience a flare (107 [70%] of 152 patients vs 72 [47%] of 153 patients; p<0·0001) up to and including week 68. Among 673 patients receiving adalimumab at any time, 516 (77%) patients reported an adverse event and 28 (4%) experienced a serious adverse event. The most common adverse events in both the adalimumab and placebo groups were nasopharyngitis (25 [16%] vs 20 [13%]), upper respiratory tract infection (20 [13%] vs 12 [8%]), and worsening of axial spondyloarthritis (ten [7%] vs 21 [14%]). INTERPRETATION In patients with active non-radiographic axial spondyloarthritis who achieved sustained remission with adalimumab, continued therapy was associated with significantly fewer patients flaring than was treatment withdrawal. FUNDING AbbVie.

Relationship Between MRI and Clinical Remission In Patients With Non-Radiographic Axial Spondyloarthritis After Two Years Of Adalimumab Therapy

SUPPLEMENTSex Bias In Autoimmune Diseases : Increased Risk Of 47,XXX In Systemic Lupus Erythematosus (SLE) and Sjogrens Syndrome (SS) Supports The Gene Dose HypothesisBackground/Purpose: Human FoxP3+ Th-cells are heterogeneous in function and include not only suppressive cells (TRegs) but also nonsuppressive cells that abundantly secrete proinflammatory cytokines. We have previously shown that FoxP3+ Th-cells were increased in GPA-patients during remission as compared to healthy controls (HCs). In this group of patients, however, we observed a defective suppressor function of TRegs, and an increase in the percentage of Th-17 cells. These observations make it tempting to investigate whether increased FoxP3+ Th-cells in GPA-patients are attributed to an increase in the cytokine-secreting non-suppressive FoxP3+Th-cells. Methods: Peripheral blood mononuclear cells (PBMCs) were isolated from 46 GPA-patients in remission and from 22 age- and sex-matched HCs. Expression of CD4, CD45RO, and FoxP3 were determined by flow cytometric analysis. The expression levels of FoxP3 and CD45RO were used for distinction between activated suppressor TRegs (FoxP3HighCD45RO+; ASTReg), resting suppressor TRegs (FoxP3LowCD45RO-; RSTReg), and cytokine-secreting non-suppressor TRegs (FoxP3LowCD45RO+; NONTReg) cells. Intracellular expression of IFNg, IL-17, and IL-21 were determined in the various FoxP3+ Th-cell subsets after in vitro activation of PBMCs by PMA and Ca-Ionophore. Results: A significant increase in the frequency of NONTReg cells was observed in GPA-patients as compared with HCs, whereas no differences were detected in RSTReg- and ASTReg cells between GPA-patients and HCs. The distribution of RSTReg- and NONTReg cells did not differ between ANCA-negative and ANCA-positive patients, whereas lower percentages of ASTReg cells were observed in ANCA-positive patients as compared to ANCA-negative patients and HCs. Importantly, a significant increase in the percentage of IL-17+ and IL-21+ cells was seen within the NONTRegcells from ANCA-positive patients (n= 9) when compared to ANCA-negative (n= 10) and HCs (n= 12), whereas no differences were found between ANCA-negative and HCs. Conclusion: Increased FoxP3 expression in Th-cells from GPA-patients is related to an increase in a subset of non-suppressive Th-cells. Increased production of IL-17 and IL-21 cytokines, in NONTReg cells from ANCApositive patients points towards FoxP3+ effector cells and decrease in suppressive TReg cells in relation to ANCA production.Complex Functional Effects Within The HLA Contribute To Sjogrens Syndrome Pathogenesis and May Influence Both Transcriptional Regulation and Peptide Binding

SAT0578 Value of Treating Both Skin and Joint Manifestations of Psoriatic Arthritis: Post-HOC Analysis of the Adept Clinical Trial

Background Psoriatic arthritis (PsA) is a complex chronic inflammatory disease associated with psoriasis that primarily affects peripheral joints. The impact of both skin and joint manifestations of PsA on disease burden is not well characterized. Objectives To assess the relative contributions of skin and joint manifestations of PsA to the overall disease burden. Methods This post-hoc analysis of the Adalimumab Effectiveness in Psoriatic Arthritis Trial (ADEPT) evaluated the subset of patients aged ≥18 years with active PsA (≥3 swollen joints and ≥3 tender joints) and an inadequate response to NSAID therapy with ≥3% body surface area [BSA] skin involvement of psoriasis. Joint damage (modified Total Sharp Score [mTSS]), physical function (Health Assessment Questionnaire disability index [HAQ-DI]), HRQoL (Short Form-36 [SF-36] and Dermatology Life Quality Index [DLQI]), pain, fatigue (Functional Assessment of Chronic Illness Therapy-Fatigue [FACIT-F]), and physicians global assessment (PGA) were assessed at baseline and week 24. Multivariate linear regression was used to investigate associations of outcomes with skin and joint manifestations in patients with moderate (Psoriasis Area and Severity Index [PASI] ≤median, 6) or high (PASI >median, 6) skin involvement and low (DAS28 <3.2), moderate (DAS28 3.2–5.1) or high (DAS28 >5.1) joint involvement, with adjustment for age, sex, body weight, PsA duration, and methotrexate use. Results 140 patients were included. At baseline, increasing skin involvement (high vs moderate after controlling for DAS28 value) was associated with worse SF-36 mental component summary score (MCS; difference = 4.2, P=0.0371), FACIT-F (difference = 5.0, P=0.0095), DLQI (difference = 4.5, P=0.0001), and PGA (difference = 6.5, P=0.0141). Greater joint involvement (high vs low and moderate vs low after controlling for PASI score) was associated with worse HAQ-DI (difference = 0.98, P<0.0001; 0.41, P=0.0097), SF-36 physical component summary score (PCS; difference = 16.0 and 9.9, both P<0.0001), pain (difference = 40.8 and 25.4, both P<0.0001), FACIT-F (difference = 12.8, P=0.0002; 4.6, P=0.1222), DLQI (difference = 5.0, P=0.0120; 1.3, P=0.4686), and PGA (difference=17.3, P=0.0003; 6.9, P=.0963). Among the 41 patients who achieved joint remission (DAS28 <2.6) at week 24, those who also achieved skin remission (PASI ≤3) experienced greater improvements in most outcomes vs those who did not (Table). Conclusions Joint manifestations of PsA contributed to impaired physical function, physical health, pain, and fatigue. Skin manifestations contributed to decreased mental health, physical health, and fatigue. Despite achievement of joint remission, patients without skin remission experienced worse physical and functional impairments, pain, and physician-assessed outcomes. Management of PsA should aim to minimize both joint and skin involvement. Acknowledgements Financial support for the study and medical writing support (Eric Bertelsen, Arbor Communications, Ann Arbor, MI) was provided by AbbVie. AbbVie participated in the interpretation of data, review, and approval of the abstract. All authors contributed to the development of the publication and maintained control over the final content. Disclosure of Interest P. Mease Grant/research support from: AbbVie, Amgen, BMS, Celgene, Genentech, Janssen, Lilly, Merck, Novartis, Pfizer, Roche, UCB, Consultant for: AbbVie, Amgen, BMS, Celgene, Genentech, Janssen, Lilly, Merck, Novartis, Pfizer, Roche, UCB, Speakers bureau: AbbVie, Amgen, BMS, Celgene, Genentech, Janssen, Lilly, Merck, Novartis, Pfizer, Roche, UCB, M. Mittal Shareholder of: AbbVie, Employee of: AbbVie, A. Joshi Shareholder of: AbbVie, Employee of: AbbVie, N. Chen Shareholder of: AbbVie, Employee of: AbbVie, J. Anderson Shareholder of: AbbVie, Employee of: AbbVie, Y. Bao Shareholder of: AbbVie, Employee of: AbbVie