Tuberculosis Risk in Ankylosing Spondylitis,Other Spondyloarthritis,and Psoriatic Arthritis in Sweden: A Population‐Based Cohort Study

Objective

Rheumatoid arthritis is a risk factor for tuberculosis (TB), particularly following treatment with biologic agents. Since these therapies are increasingly used in ankylosing spondylitis (AS), other types of spondyloarthritis (SpA), and psoriatic arthritis (PsA), we investigated the corresponding TB risks in these patients.

Methods

We identified individuals with AS/SpA/PsA, and non‐AS/SpA/PsA comparators by linking Swedish national patient, population, TB, and rheumatology registers, and followed them for TB occurrence. Incidence rates were estimated for biologic‐naive and biologic‐exposed patients and the comparators. We calculated hazard ratios (HRs), adjusted for age, sex, and country of birth.

Results

Included in this study were 38,702 patients with AS/SpA/PsA, and 200,417 persons from the general population. Among the patients, 11 active TB cases were identified, with an incidence rate (per 10⁵) of 22 (95% confidence interval [95% CI] 8.3–59.2) for biologic‐exposed patients, 2.7 (95% CI 1.3–5.6) for biologic‐naive patients, and 2.4 (95% CI 1.8–3.3) for non‐AS/SpA/PsA comparators. The adjusted HR comparing biologic‐naive patients to the general population was 1.2 (95% CI 0.5–2.7), and 7.5 (95% CI 1.9–29) comparing biologic‐exposed to biologic‐naive patients.

Conclusion

Biologic‐naive AS/SpA/PsA patients are not at an increased TB risk in Sweden. Following treatment with biologic agents, the risk increased, but the absolute TB risk was low.

     

Financial Incentives and Health Coaching to Improve Physical Activity Following Total Knee Replacement: A Randomized Controlled Trial

Objective

Most persons who undergo total knee replacement (TKR) do not increase their physical activity following surgery. We assessed whether financial incentives and health coaching would improve physical activity in persons undergoing TKR.

Methods

We designed a factorial randomized controlled trial among persons undergoing TKR for osteoarthritis. Subjects underwent normal perioperative procedures, including postoperative physical therapy, and were assigned to 1 of 4 arms: attention control, telephonic health coaching (THC), financial incentives (FI), or THC + FI. We objectively measured step counts and minutes of physical activity using a commercial accelerometer (Fitbit Zip) and compared the changes from pre‐TKR to 6 months post‐TKR across the 4 study arms.

Results

Of the 202 randomized subjects, 150 (74%) provided both pre‐TKR and 6 months post‐TKR accelerometer data. Among completers, the mean ± SE daily step count at 6 months ranged from 5,619 ± 381 in the THC arm to 7,152 ± 407 in the THC + FI arm (adjusting for baseline values). Daily step count 6 months post‐TKR increased by 680 (95% confidence interval [95% CI] ?94, 1,454) in the control arm, 274 (95% CI ?473, 1,021) in the THC arm, 826 (95% CI 89, 1,563) in the FI arm, and 1,808 (95% CI 1,010, 2,606) in the THC + FI arm. Weekly physical activity increased by mean ± SE 14 ± 10, 14 ± 10, 16 ± 10, and 39 ± 11 minutes in the control, THC, FI, and THC + FI arms, respectively.

Conclusion

A dual THC + FI intervention led to substantial improvements in step count and physical activity following TKR.

     

Association of Comorbidities in Spondyloarthritis With Poor Function,Work Disability,and Quality of Life: Results From the Assessment of SpondyloArthritis International Society Comorbidities in Spondyloarthritis Study

Objective

Comorbidities add to the burden of disease and its complexity, and may prevent the achievement of treat‐to‐target goals. The objective of this study was to study the relationship between comorbidities and key disease outcomes in spondyloarthritis (SpA), namely function, work ability, and quality of life.

Methods

Patients from the multinational (22 countries), cross‐sectional Assessment in SpondyloArthritis international Society (ASAS) Comorbidities in Spondyloarthritis study were included in the analysis, provided they fulfilled the ASAS criteria. Data on comorbidities based on both self‐ and physician‐report were collected through questionnaires and were subsequently used to compute the Rheumatic Disease Comorbidity Index (RDCI). Univariable and multivariable (adjusted for relevant confounders) multilevel (with country as a random effect) linear or logistic (as appropriate) regression analyses were conducted to investigate the relationship between the RDCI and functional ability, work ability, and quality of life.

Results

In total, 3,370 of 3,984 recruited patients (85%) fulfilled the ASAS criteria: 66% were male, mean ± SD age was 43 ± 14 years, mean ± SD disease duration was 8.4 ± 9.5 years, and mean ± SD RDCI was 0.7 ± 1.1. At least 1 comorbidity was reported in 51% of patients; 9% had ≥3 comorbidities. RDCI was independently associated with a higher Bath Ankylosing Spondylitis Functional Index score (β = 0.37, 95% confidence interval [95% CI] 0.30, 0.43), lower EuroQol 5‐domain questionnaire (β = ?0.03, 95% CI ?0.04, ?0.02), less work employment (odds ratio [OR] 0.83, 95% CI 0.76, 0.91), higher absenteeism (OR 1.18, 95% CI 1.04, 1.34), and higher presenteeism (OR 1.42, 95% CI 1.26, 1.61).

Conclusion

Comorbidities in SpA adversely influence physical function, work ability, and quality of life and are important to take into account in daily clinical practice.

     

Minimum Performance on Clinical Tests of Physical Function to Predict Walking 6,000 Steps/Day in Knee Osteoarthritis: An Observational Study

Objective

Evidence of physical function difficulties, such as difficulty rising from a chair, may limit daily walking for people with knee osteoarthritis (OA). The purpose of this study was to identify minimum performance thresholds on clinical tests of physical function predictive to walking ≥6,000 steps/day. This benchmark is known to discriminate people with knee OA who develop functional limitation over time from those who do not.

Methods

Using data from the Osteoarthritis Initiative, we quantified daily walking as average steps/day from an accelerometer (Actigraph GT1M) worn for ≥10 hours/day over 1 week. Physical function was quantified using 3 performance‐based clinical tests: 5 times sit‐to‐stand test, walking speed (tested over 20 meters), and 400‐meter walk test. To identify minimum performance thresholds for daily walking, we calculated physical function values corresponding to high specificity (80–95%) to predict walking ≥6,000 steps/day.

Results

Among 1,925 participants (mean ± SD age 65.1 ± 9.1 years, mean ± SD body mass index 28.4 ± 4.8 kg/m², and 55% female) with valid accelerometer data, 54.9% walked ≥6,000 steps/day. High specificity thresholds of physical function for walking ≥6,000 steps/day ranged 11.4–14.0 seconds on the 5 times sit‐to‐stand test, 1.13–1.26 meters/second for walking speed, or 315–349 seconds on the 400‐meter walk test.

Conclusion

Not meeting these minimum performance thresholds on clinical tests of physical function may indicate inadequate physical ability to walk ≥6,000 steps/day for people with knee OA. Rehabilitation may be indicated to address underlying impairments limiting physical function.

     

Effects of a Web‐Based Patient Decision Aid on Biologic and Small‐Molecule Agents for Rheumatoid Arthritis: Results From a Proof‐of‐Concept Study

Objective

To assess the extent to which ANSWER‐2, an interactive online patient decision aid, reduces patients’ decisional conflict and improves their medication‐related knowledge and self‐management capacity.

Methods

We used a pre–post study design. Eligible participants had a diagnosis of rheumatoid arthritis (RA), had been recommended to start using a biologic agent or small‐molecule agent or to switch to a new one, and had internet access. Access to ANSWER‐2 was provided immediately after enrollment. Outcome measures included 1) the Decisional Conflict Scale (DCS), 2) the Medication Education Impact Questionnaire (MeiQ), and 3) the Partners in Health Scale (PIHS). A paired t‐test was used to assess differences pre‐ and postintervention.

Results

The majority of the 50 participants were women (n = 40), and the mean ± SD age of participants was 49.6 ± 12.2 years. The median disease duration was 5 years (25th, 75th percentile: 2, 10 years). The mean ± SD DCS score was 45.9 ± 25.1 preintervention and 25.1 ± 21.8 postintervention (mean change of ?21.2 of 100 [95% confidence interval (95% CI) ?28.1, ?14.4], P < 0.001). Before using ANSWER‐2, 20% of participants had a DCS score of <25, compared to 52% of participants after the intervention. Similar results were observed in the PIHS (mean ± SD 25.3 ± 14.8 preintervention and 20.4 ± 13.0 postintervention; mean change of ?3.7 of 88 [95% CI ?6.3, ?1.0], P = 0.009). Findings from the MeiQ were mixed, with statistically significant differences found only in the self‐management subscales.

Conclusion

Patients’ decisional conflict decreased and perceived self‐management capacity improved after using ANSWER‐2. Future research comparing the effectiveness of ANSWER‐2 with that of educational material on biologic agents will provide further insight into its value in RA management.

     

Subjective and Objective Measures of Dryness Symptoms in Primary Sjögren's Syndrome: Capturing the Discrepancy

Objective

To develop a novel method for capturing the discrepancy between objective tests and subjective dryness symptoms (a sensitivity scale) and to explore predictors of dryness sensitivity.

Methods

Archive data from the UK Primary Sjögren's Syndrome Registry (n = 688) were used. Patients were classified on a scale from ?5 (stoical) to +5 (sensitive) depending on the degree of discrepancy between their objective and subjective symptoms classes. Sensitivity scores were correlated with demographic variables, disease‐related factors, and symptoms of pain, fatigue, anxiety, and depression.

Results

Patients were on average relatively stoical for both types of dryness symptoms (mean ± SD ocular dryness ?0.42 ± 2.2 and ?1.24 ± 1.6 oral dryness). Twenty‐seven percent of patients were classified as sensitive to ocular dryness and 9% to oral dryness. Hierarchical regression analyses identified the strongest predictor of ocular dryness sensitivity to be self‐reported pain and that of oral dryness sensitivity to be self‐reported fatigue.

Conclusion

Ocular and oral dryness sensitivity can be classified on a continuous scale. The 2 symptom types are predicted by different variables. A large number of factors remain to be explored that may impact symptom sensitivity in primary Sjögren?s syndrome, and the proposed method could be used to identify relatively sensitive and stoical patients for future studies.

     

Efficacy of Hydroxychloroquine in Hand Osteoarthritis: A Randomized,Double‐Blind,Placebo‐Controlled Trial

Objective

To determine the symptom‐modifying effect of hydroxychloroquine (HCQ) in hand osteoarthritis (OA).

Methods

In this randomized, double‐blind, multicenter trial, patients with symptomatic hand OA received either HCQ 400 mg once a day or placebo during 24 weeks. The primary outcome was change of pain measured on a 100‐mm visual analog scale (VAS) at 24 weeks. Secondary outcomes included decrease of pain at weeks 6 and 12 and change in Australian Canadian Hand Osteoarthritis Index (AUSCAN) and Arthritis Impact Measurement Scale 2 short form (AIMS2‐SF) total scores.

Results

A total of 196 patients was included (placebo n = 98, HCQ n = 98). Mean ± SD age was 58.0 ± 7.6 years, and 86% were female. Baseline mean ± SD pain VAS was 44.9 ± 22.9 mm in the placebo group and 43.2 ± 22.3 mm in the HCQ group. At 24 weeks, change in pain VAS was not significantly different between both groups (imputed mean VAS 42.7 in the HCQ group versus 45.3 in the placebo group after 24 weeks), as was the case in pain VAS at weeks 6 and 12. Changes in AUSCAN total score and AIMS2‐SF total score in both groups were similar between the groups. In total, 24 patients in the placebo group and 21 patients in the HCQ group reported ≥1 adverse event. In the HCQ group, 3 patients reported a severe allergic reaction. Fifteen patients withdrew from the study (5 placebo, 10 HCQ group) due to adverse events.

Conclusion

Treatment with HCQ at 24 weeks is not effective in reducing the symptoms of hand OA compared to placebo.

     

Dyslipidemia,Alcohol Consumption,and Obesity as Main Factors Associated With Poor Control of Urate Levels in Patients Receiving Urate‐Lowering Therapy

Objective

In real life, in a substantial proportion of gouty patients receiving urate‐lowering therapy (ULT), urate levels are not maintained below the target of 6.0 mg/dl. We aimed to search for factors associated with poor control of serum uric acid (UA) levels in a large population of patients with gout receiving ULT.

Methods

This cross‐sectional study involved adults with gout in primary care who were receiving ULT. Demographics, gout history, comorbidities, lifestyle, clinical factors, concomitant treatments, and laboratory data were compared in well‐controlled gout (serum UA ≤6.0 mg/dl) versus poorly controlled gout (serum UA >6.0 mg/dl) on univariate and multivariate analyses.

Results

Among the 1,995 patients receiving ULT, only 445 (22.3%) had reached the target of 6.0 mg/dl serum UA. Such patients had a lower rate of gout flares within the previous year than patients without the target (mean ± SD 1.7 ± 1.4 versus 2.1 ± 1.4; P < 0.0001). The main factors associated with poor serum UA level control in multivariate analysis were low high‐density lipoprotein cholesterol level (adjusted odds ratio [OR] 0.5 [95% confidence interval (95% CI) 0.26–0.96]; P = 0.04), high total cholesterol level (OR 1.83 [95% CI 1.29–2.60]; P = 0.0007), increased waist circumference (OR 1.55 [95% CI 1.11–2.13]; P = 0.008), and alcohol consumption (OR 1.52 [95% CI 1.15–2.00]; P = 0.003).

Conclusion

Dyslipidemia, abdominal obesity, and alcohol consumption are the main factors associated with a poor response to ULT. Knowledge of these factors might help physicians identify cases of gout that may be less likely to achieve target urate level.

     

Economic Evaluation of Lupus Nephritis in the Systemic Lupus International Collaborating Clinics Inception Cohort Using a Multistate Model Approach

Objective

Little is known about the long‐term costs of lupus nephritis (LN). The costs were compared between patients with and without LN using multistate modeling.

Methods

Patients from 32 centers in 11 countries were enrolled in the Systemic Lupus International Collaborating Clinics inception cohort within 15 months of diagnosis and provided annual data on renal function, hospitalizations, medications, dialysis, and selected procedures. LN was diagnosed by renal biopsy or the American College of Rheumatology classification criteria. Renal function was assessed annually using the estimated glomerular filtration rate (GFR) or estimated proteinuria. A multistate model was used to predict 10‐year cumulative costs by multiplying annual costs associated with each renal state by the expected state duration.

Results

A total of 1,545 patients participated; 89.3% were women, the mean ± age at diagnosis was 35.2 ± 13.4 years, 49% were white, and the mean followup duration was 6.3 ± 3.3 years. LN developed in 39.4% of these patients by the end of followup. Ten‐year cumulative costs were greater in those with LN and an estimated glomerular filtration rate (GFR) <30 ml/minute ($310,579 2015 Canadian dollars versus $19,987 if no LN and estimated GFR >60 ml/minute) or with LN and estimated proteinuria >3 gm/day ($84,040 versus $20,499 if no LN and estimated proteinuria <0.25 gm/day).

Conclusion

Patients with estimated GFR <30 ml/minute incurred 10‐year costs 15‐fold higher than those with normal estimated GFR. By estimating the expected duration in each renal state and incorporating associated annual costs, disease severity at presentation can be used to anticipate future health care costs. This is critical knowledge for cost‐effectiveness evaluations of novel therapies.

     

Risk of Allergic Conditions in Children Born to Women With Systemic Lupus Erythematosus

Objective

Limited evidence suggests a potentially increased risk of allergic conditions in offspring born to women with systemic lupus erythematosus (SLE). In a large population‐based study, we aimed to determine if children born to mothers with SLE have an increased risk of allergic conditions compared to children born to mothers without SLE.

Methods

Using the Offspring of SLE Mothers Registry, we identified children born live to mothers with SLE and their matched controls, and ascertained the number of allergic conditions (asthma, allergic rhinitis, eczema, urticaria, angioedema, and anaphylaxis) based on ≥1 hospitalization or ≥1 or 2 physician(s) visit(s) with a relevant diagnostic code. We adjusted for maternal age, education, race/ethnicity, obstetrics complications, calendar year of birth, sex of the child, and maternal medication.

Results

There were 509 women with SLE who had 719 children, while 5,824 matched controls had 8,493 children. The mean ± SD followup period was 9.1 ± 5.8 years. Compared to controls, more children born to mothers with SLE had evidence of allergic conditions (43.9% [95% confidence interval (95% CI) 40.4–47.6] versus 38.1% [95% CI 37.0–39.1]). In multivariate analysis (n = 9,212), children born to mothers with SLE had an increased risk of allergic conditions versus control children (odds ratio 1.35 [95% CI 1.13–1.61]).

Conclusion

Compared to children from the general population, children born to women with SLE may have an increased risk of allergic conditions. Genetics, shared environmental exposures, as well as in utero exposure to maternal autoantibodies and cytokines may mediate this increased risk.

     

Tele‐Health Followup Strategy for Tight Control of Disease Activity in Rheumatoid Arthritis: Results of a Randomized Controlled Trial

Objective

To test the effect of patient‐reported outcome (PRO)–based tele‐health followup for tight control of disease activity in patients with rheumatoid arthritis (RA), and the differences between tele‐health followup performed by rheumatologists or rheumatology nurses.

Methods

A total of 294 patients were randomized (1:1:1) to either PRO‐based tele‐health followup carried out by a nurse (PRO‐TN) or a rheumatologist (PRO‐TR), or conventional outpatient followup by physicians. The primary outcome was a change in the Disease Activity Score in 28 joints (DAS28) after week 52. Secondary outcomes were physical function, quality of life, and self‐efficacy. The noninferiority margin was a DAS28 score change of 0.6. Mean differences were estimated following per protocol, intent‐to‐treat (ITT), and multivariate imputation analysis.

Results

Overall, patients had low disease activity at baseline and end followup. Demographics and baseline characteristics were similar between groups. Noninferiority was established for the DAS28. In the ITT analysis, mean differences in the DAS28 score between PRO‐TR versus control were ?0.10 (90% confidence interval [90% CI] ?0.30, 0.13) and ?0.19 (90% CI ?0.41, 0.02) between PRO‐TN versus control. When including 1 yearly visit to the outpatient clinic, patients in PRO‐TN had mean ± SD 1.72 ± 1.03 visits/year, PRO‐TR had 1.75 ± 1.03 visits/year, and controls had 4.15 ± 1.0 visits/year. This included extra visits due to inflammatory flare.

Conclusion

Among RA patients with low disease activity or remission, a PRO‐based tele‐health followup for tight control of disease activity in RA can achieve similar disease control as conventional outpatient followup. The degree of disease control did not differ between patients seen by rheumatologists or rheumatology nurses.

     

Pelvic and Hip Kinematics During Walking in People With Patellofemoral Joint Osteoarthritis Compared to Healthy Age‐Matched Controls

Objective

Patellofemoral (PF) joint osteoarthritis (OA) is common, yet little is known about how this condition influences lower‐extremity biomechanical function. This study compared pelvis and lower‐extremity kinematics in people with and without PF joint OA.

Methods

Sixty‐nine participants (64% women, mean ± SD age 56 ± 10 years) with anterior knee pain aggravated by PF joint–loaded activities (e.g., stair ambulation, rising from sitting, or squatting) and radiographic lateral PF joint OA on skyline radiographs were compared with 18 controls (78% women, mean ± SD age 53 ± 7 years) with no lower‐extremity pain or radiographic OA. Knee Injury and Osteoarthritis Outcome Score (KOOS) data were collected from participants with PF joint OA. Quantitative gait analyses were conducted during overground walking at a self‐selected speed. Pelvis and lower‐extremity kinematics were calculated across the stance phase. Data were statistically analyzed using analyses of covariance, with age and sex as covariates (P < 0.05).

Results

Participants with PF joint OA reported a mean ± SD KOOS pain subscale score of 65 ± 15, KOOS symptoms subscale score of 63 ± 16, KOOS activities of daily living subscale score of 73 ± 13, KOOS sports/recreation subscale score of 45 ± 23, and KOOS quality of life subscale score of 43 ± 16. Participants with PF joint OA walked with greater anterior pelvic tilt throughout the stance phase, as well as greater lateral pelvic tilt (i.e., pelvis lower on the contralateral side), greater hip adduction, and lower hip extension during the late stance phase. No differences in knee and ankle joint angles were observed between groups.

Conclusion

People with PF joint OA walk with altered pelvic and hip movement patterns compared with aged‐matched controls. Restoring normal movement patterns during walking in people with PF joint OA may be warranted to help alleviate symptoms.

     

Efficacy of a Work Disability Prevention Program for People with Rheumatic and Musculoskeletal Conditions: A Single‐Blind Parallel‐Arm Randomized Controlled Trial

Objective

Work disability rates are high among people with rheumatic and musculoskeletal conditions. Effective disability preventive programs are needed. We examined the efficacy of a modified vocational rehabilitation approach delivered by trained occupational therapists and physical therapists on work limitation and work loss over 2 years among people with rheumatic and musculoskeletal conditions.

Methods

Eligibility criteria for this single‐blind, parallel‐arm randomized trial included ages 21–65 years, 15 or more hours/week employment, a self‐reported doctor‐diagnosed rheumatic or musculoskeletal condition, and concern about staying employed. The intervention consisted of a 1.5‐hour meeting, an action plan, written materials on employment supports, and telephone calls at 3 weeks and 3 months. Control group participants received the written materials. The primary outcome was the Work Limitations Questionnaire (WLQ) output job demand subscale. The secondary outcome was work loss. Intent‐to‐treat analyses were performed.

Results

Between October 2011 and January 2014, 652 individuals were assessed for eligibility. A total of 287 participants were randomized: 143 intervention and 144 control participants. In total, 264 participants (92%) completed 2‐year data collection. There was no difference in the mean ± SD WLQ change scores from baseline to 2‐year followup (?8.6 ± 1.9 intervention versus ?8.3 ± 2.2 control; P = 0.93). Of the 36 participants who experienced permanent work loss at 2 years, 11 (8%) were intervention participants and 25 (18%) control participants (P = 0.03).

Conclusion

The intervention did not have an effect on work limitations but reduced work loss. The intervention can be delivered by trained rehabilitation therapists.

     

Comparison of the Lupus Foundation of America–Rapid Evaluation of Activity in Lupus to More Complex Disease Activity Instruments As Evaluated by Clinical Investigators or Real‐World Clinicians

Objective

Lupus disease measures such as the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and the British Isles Lupus Assessment Group (BILAG) index are challenging to interpret. The Lupus Foundation of America–Rapid Evaluation of Activity in Lupus (LFA‐REAL) is intended to provide an efficient application of anchored visual analog scores, each representing the individual severity of active symptoms, with the sum of individual scores deriving an overall disease activity assessment. Our objective was to compare the performance of LFA‐REAL to systemic lupus erythematosus disease activity assessments and compare scores between trained lupus clinical investigators and clinicians.

Methods

Investigators scored the SLEDAI, BILAG, physician's global assessment (PGA), and LFA‐REAL, while the clinicians scored the LFA‐REAL. The level of agreement between physicians and instruments was determined.

Results

The study included 99 patients (93% women, 31% white, mean ± SD ages 43.4 ± 13.2 years). At the first visit, the mean ± SD SLEDAI score was 5.5 ± 4.5, BILAG score 6.7 ± 7.8, and PGA score 33.6 ± 24.5. The mean ± SD investigator LFA‐REAL score was 46.2 ± 42.9, and clinician LFA‐REAL score 56.1 ± 53.6. At the second visit, the mean ± SD investigator LFA‐REAL score was 41.3 ± 36.7, and clinician LFA‐REAL score 48.3 ± 42.6. Total LFA‐REAL scores correlated positively with PGA, SLEDAI, and BILAG (ρ = 0.58–0.88, P < 0.001). LFA‐REAL scores produced correlation coefficients of ρ > 0.7 for musculoskeletal, mucocutaneous, and renal BILAG domains. The intraclass correlation coefficient between the LFA‐REAL scores of investigators and clinicians was 0.79 for visit 1 (P < 0.001) and 0.86 for visit 2 (P < 0.001).

Conclusion

The LFA‐REAL provides a reliable surrogate for more complicated disease activity measures when used by lupus clinical investigators or clinicians.

     

Flares After Withdrawal of Biologic Therapies in Juvenile Idiopathic Arthritis: Clinical and Laboratory Correlates of Remission Duration

Objective

To assess the time in remission after discontinuing biologic therapy in patients with juvenile idiopathic arthritis (JIA).

Methods

We enrolled 135 patients followed in 3 tertiary‐care centers. The primary outcome was to assess, once remission was achieved, the time in remission up to the first flare after discontinuing treatment. Mann‐Whitney U test, Wilcoxon's signed rank test for paired samples, chi‐square tests, and Fisher's exact test were used to compare data. Pearson's and Spearman's correlation tests were used to determine correlation coefficients for different variables. To identify predictors of outcome, Cox regression model and Kaplan‐Meier curves were constructed, each one at the mean of entered covariates.

Results

The majority of enrolled patients flared after stopping treatment with biologics (102 of 135, 75.6%) after a median followup time in remission off therapy of 6 months (range 3–109 months). A higher probability of maintaining remission after discontinuing treatment was present in systemic‐onset disease compared to the rest of the JIA patients (Mantel‐Cox χ² = 8.31, P < 0.004). In analysis limited to children with JIA with polyarticular and oligoarticular disease, patients who received biologics >2 years after achieving remission had a higher probability of maintaining such remission off therapy (mean ± SD 18.64 ± 3.3 months versus 11.51 ± 2.7 months [P < 0.009]; Mantel‐Cox χ² = 9.06, P < 0.002). No other clinical variable was significantly associated with a long‐lasting remission.

Conclusion

Children with oligoarticular and polyarticular JIA who stop treatment before 2 years from remission have a higher chance of relapsing after biologic withdrawal.

     

Treatment of Chronic Chikungunya Arthritis With Methotrexate: A Systematic Review

Objective

Chikungunya virus infection is a rapidly emerging global viral infection that can cause chronic, debilitating arthritis that in some ways mimics rheumatoid arthritis. The aim of this study was to evaluate the available evidence regarding the efficacy and safety of methotrexate (MTX), a therapy that is widely used in rheumatoid arthritis, for the treatment of chronic chikungunya arthritis.

Methods

A systematic literature search was performed to identify all published trials that evaluated MTX as monotherapy or combination therapy in patients with chronic chikungunya arthritis. PubMed, SciELO, Scopus, and Cochrane Library databases were searched from study inception to August 2017. We also searched Google Scholar, the International Clinical Trials Registry Platform Search Portal, and clinicaltrials.gov.

Results

Among 131 possibly relevant studies, 6 met our criteria for evaluation: 4 were retrospective studies, 1 was a non‐controlled prospective study, and 1 was an unblinded randomized clinical trial of combination MTX therapy. In the randomized clinical trial, triple therapy with MTX, hydroxychloroquine, and sulfasalazine was superior to hydroxychloroquine monotherapy, as assessed by the mean ± SD Disease Activity Score in 28 joints using the erythrocyte sedimentation rate (3.39 ± 0.87 versus 4.74 ± 0.65; P < 0.0001) and the Health Assessment Questionnaire score (1.14 ± 0.31 versus 1.88 ± 0.47; P < 0.0001).

Conclusion

The number of available studies is limited, but taken together, these studies demonstrate that MTX is sufficiently efficacious to justify further study of MTX for the treatment of chronic chikungunya arthritis. The trials lacked rigorous study designs and used different treatment strategies and outcome measures. This systematic review underscores the need for randomized, prospective, placebo‐controlled studies of MTX monotherapy for the treatment of chronic chikungunya arthritis.

     

Quantifying Digital Ulcers in Systemic Sclerosis: Reliability of Computer‐Assisted Planimetry in Measuring Lesion Size

Objective

Digital ulcers are a major problem in patients with systemic sclerosis (SSc), causing severe pain and impairment of hand function. In addition, digital ulcers heal slowly and sometimes become infected, which can lead to gangrene and necessitate amputation if appropriate intervention is not taken. A reliable, objective method for assessing digital ulcer healing or progression is needed in both the clinical and research arenas. This study was undertaken to compare 2 computer‐assisted planimetry methods of measurement of digital ulcer area on photographs (ellipse and freehand regions of interest [ROIs]), and to assess the reliability of photographic calibration and the 2 methods of area measurement.

Methods

Photographs were taken of 107 digital ulcers in 36 patients with SSc spectrum disease. Three raters assessed the photographs. Custom software allowed raters to calibrate photograph dimensions and draw ellipse or freehand ROIs. The shapes and dimensions of the ROIs were saved for further analysis.

Results

Calibration (by a single rater performing 5 repeats per image) produced an intraclass correlation coefficient (intrarater reliability) of 0.99. The mean ± SD areas of digital ulcers assessed using ellipse and freehand ROIs were 18.7 ± 20.2 mm² and 17.6 ± 19.3 mm², respectively. Intrarater and interrater reliability of the ellipse ROI were 0.97 and 0.77, respectively. For the freehand ROI, the intrarater and interrater reliability were 0.98 and 0.76, respectively.

Conclusion

Our findings indicate that computer‐assisted planimetry methods applied to SSc‐related digital ulcers can be extremely reliable. Further work is needed to move toward applying these methods as outcome measures for clinical trials and in clinical settings.

     

Relationship Between Fish Consumption and Disease Activity in Rheumatoid Arthritis

Objective

To assess whether more frequent fish consumption is associated with lower rheumatoid arthritis (RA) disease activity scores among participants in an RA cohort.

Methods

We conducted a cross‐sectional analysis using baseline data from participants in the Evaluation of Subclinical Cardiovascular Disease and Predictors of Events in Rheumatoid Arthritis cohort study. Frequency of fish consumption was assessed by a baseline food frequency questionnaire assessing usual diet in the past year. Multivariable, total energy–adjusted linear regression models provided effect estimates and 95% confidence intervals (95% CIs) for frequency of fish consumption (i.e., never to <1 time/month, 1 time/month to <1 time/week, 1 time/week, and ≥2 times/week) on baseline Disease Activity Score in 28 joints (DAS28) using the C‐reactive protein (CRP) level. We also estimated the difference in DAS28‐CRP associated with increasing fish consumption by 1 serving per week.

Results

Among 176 participants, the median DAS28‐CRP score was 3.5 (interquartile range 2.9–4.3). In an adjusted linear regression model, subjects consuming fish ≥2 times/week had a significantly lower DAS28‐CRP compared with subjects who ate fish never to <1 time/month (difference ?0.49 [95% CI ?0.97, ?0.02]). For each additional serving of fish per week, DAS28‐CRP was significantly reduced by 0.18 (95% CI ?0.35, ?0.004).

Conclusion

Our findings suggest that higher intake of fish may be associated with lower disease activity in RA patients.

     

Association of Vitamin K Status Combined With Vitamin D Status and Lower‐Extremity Function: A Prospective Analysis of Two Knee Osteoarthritis Cohorts

Objective

Vitamins K and D are important for the function of vitamin K–dependent proteins in joint tissues. It is unclear whether these nutrients are mutually important to functional outcomes related to knee osteoarthritis (OA). We evaluated the association of vitamin K and D sufficiency with lower‐extremity function in the Health, Aging and Body Composition knee OA substudy (Health ABC) and conducted a replication analysis in an independent cohort, the Osteoarthritis Initiative (OAI).

Methods

In Health ABC (60% female, mean ± SD age 75 ± 3 years) baseline nutrient status was measured using circulating vitamin K and 25‐hydroxyvitamin D (25[OH]D). Lower‐extremity function was assessed using the Short Physical Performance Battery (SPPB) and usual 20‐meter gait speed. In the OAI (58% female, mean ± SD age 61 ± 9 years), baseline nutrient intake was estimated by food frequency questionnaire. Lower‐extremity function was assessed using usual 20‐meter gait speed and chair stand completion time. Multivariate mixed models were used to evaluate the association of vitamin K and D status and intake with lower‐extremity function over 4–5 years.

Results

Health ABC participants with sufficient plasma vitamin K (≥1.0 nmoles/liter) and serum 25(OH)D (≥50 nmoles/liter) generally had better SPPB scores and faster usual gait speed over followup (P ≤ 0.002). In the OAI, sufficient vitamin K and vitamin D intake combined was associated with overall faster usual gait speed and chair stand completion time over followup (P ≤ 0.029).

Conclusion

Sufficient vitamin K status combined with sufficient vitamin D status was associated with better lower‐extremity function in 2 knee OA cohorts. These findings merit confirmation in vitamin K and D co‐supplementation trials.

     

Association Between Anti–Citrullinated Fibrinogen Antibodies and Coronary Artery Disease in Rheumatoid Arthritis

Objective

Antibodies against citrullinated fibrinogen (anti–Cit‐fibrinogen) have been implicated in rheumatoid arthritis (RA) and associated with cardiovascular risk in RA. The objective of this study was to examine the association between anti–Cit‐fibrinogens and coronary artery disease (CAD) outcomes.

Methods

We performed the study in an RA cohort based in a large academic institution linked with electronic medical record data containing information on CAD outcomes from medical record review. Using a published bead‐based assay method, we measured 10 types of anti–Cit‐fibrinogens. We applied a score test to determine the association between the anti–Cit‐fibrinogens as a group with CAD outcomes. Principal components analysis (PCA) was performed to assess whether the anti–Cit‐fibrinogens clustered into groups. Each group was then additionally tested for association with CAD. Sensitivity analyses were also performed using a published International Classification of Disease, Ninth Revision code group for ischemic heart disease (IHD) as the outcome.

Results

We studied 1,006 RA subjects (mean ± SD age 61.0 ± 13.0 years; 72.2% anti–cyclic citrullinated peptide positive). As a group, anti–Cit‐fibrinogen was associated with CAD (P = 1.1 × 10^?4). From the PCA analysis, we observed 3 main groups, of which only 1 group, containing 7 of the 10 anti–Cit‐fibrinogens, was significantly associated with CAD outcomes (P = 0.015). In the sensitivity analysis, all anti–Cit‐fibrinogens as a group remained significantly associated with IHD (P = 2.9 × 10^?4).

Conclusion

Anti–Cit‐fibrinogen antibodies as a group were associated with CAD outcomes in our RA cohort, with the strongest signal for association arising from a subset of the autoantibodies.