Radiographic Progression in Psoriatic Arthritis Achieving a Good Response to Treatment: Data Using Newer Composite Indices of Disease Activity

Objective

To compare radiographic outcomes according to the magnitude of the response utilizing 3 new psoriatic composite disease activity measures (the Psoriatic Arthritis Disease Activity Score [PASDAS], the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis Composite Exercise [GRACE], and the Disease Activity in PsA [DAPSA]).

Methods

The data were taken from the GO‐REVEAL data set, a large randomized, double‐blind study that evaluated the safety and efficacy of 2 doses of the tumor necrosis factor inhibitor golimumab in subjects with active psoriatic arthritis (PsA). Response criteria at 24 weeks were applied across the whole data set, irrespective of treatment group. Radiographic scores at baseline and 24 weeks were assessed using the modified Sharp/van der Heijde method for PsA.

Results

Overall, for each measure, radiographic progression was significantly greater in subjects with a moderate or poor outcome, and absent in those with a good outcome. The proportion of subjects without radiographic progression in the good outcome group was 83% using the PASDAS (χ² = 7.9; P = 0.02), 80% using the GRACE (χ² = 5.8; P = 0.05), and 76% using the DAPSA (χ² = 3.4; P = 0.19).

Conclusion

Response criteria for disease‐specific composite measures enable separation between groups in terms of radiographic progression and may therefore be used as suitable targets for interventional studies, as well as in the clinic.

     

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.

     

Reductions in Radiographic Progression in Early Rheumatoid Arthritis Over Twenty‐Five Years: Changing Contribution From Rheumatoid Factor in Two Multicenter UK Inception Cohorts

Objective

To assess the 5‐year progression of erosions and joint space narrowing (JSN ) and their associations with rheumatoid factor (RF ) status in 2 large, multicenter, early rheumatoid arthritis cohorts, spanning 25 years.

Methods

Radiographic joint damage was recorded using the Sharp/van der Heijde (SHS ) method in the Early Rheumatoid Arthritis Study (ERAS ), 1986–2001, and the Early Rheumatoid Arthritis Network (ERAN ), 2002–2013. Mixed‐effects negative binomial regression estimated changes in radiographic damage over 5 years, including erosions and JSN , separately. RF , along with age, sex, and baseline markers of disease activity were controlled for.

Results

A total of 1,216 patients from ERAS and 446 from ERAN had radiographic data. Compared to ERAS , ERAN patients had a lower mean total SHS score at baseline (ERAN 6.2 versus ERAS 10.5; P < 0.001) and mean annual rate of change (ERAN 2.5 per year versus ERAS 6.9 per year; P < 0.001). Seventy‐four percent of ERAS and 27% of ERAN patients progressed ≥5 units. Lower scores at baseline in ERAN were largely driven by reductions in JSN (ERAS 3.9 versus ERAN 1.2; P < 0.001), along with erosions (ERAS 1.9 versus ERAN 0.8; P < 0.001). RF was associated with greater progression in each cohort, but the absolute difference in mean annual rate of change for RF ‐positive patients was substantially higher for ERAS (RF positive 8.6 versus RF negative 5.1; P < 0.001), relative to ERAN (RF positive 2.0 versus RF negative 1.9; P = 0.855).

Conclusion

Radiographic progression was shown to be significantly reduced between the 2 cohorts, and was associated with lower baseline damage and other factors, including changes in early disease‐modifying antirheumatic drug use. The impact of RF status as a prognostic marker of clinically meaningful change in radiographic progression has markedly diminished in the context of more modern treatment.

     

Timing and Impact of Decisions to Adjust Disease‐Modifying Antirheumatic Drug Therapy for Rheumatoid Arthritis Patients With Active Disease

Objective

Guidelines recommend that rheumatoid arthritis (RA) patients with moderate‐to‐high disease activity (MHDAS) adjust disease‐modifying antirheumatic drug (DMARD) therapy at least every 3 months until reaching low disease activity or remission (LDAS). We examined how quickly RA patients with MHDAS adjust DMARD therapy in clinical practice, and whether those who adjust DMARDs within 90 days in response to MHDAS reach LDAS sooner.

Methods

We identified RA patients with MHDAS in the University of Pittsburgh Rheumatoid Arthritis Comparative Effectiveness Research registry, and conducted a competing risks regression on time to DMARD therapy adjustment and a Cox regression on time to LDAS.

Results

We identified 538 eligible subjects with 943.5 patient‐years of followup. Sixty percent of patients with persistent MHDAS adjusted DMARDs within 90 days. Among all subjects, median times to DMARD adjustment and LDAS were 154 (interquartile range [IQR] 1–706) days and 301 (IQR 140–706) days, respectively. Being elderly (subdistribution hazard ratio [SHR] 0.61, P = 0.02), lower baseline disease activity (SHR 0.72, P < 0.01), longer duration of RA (SHR 0.98, P < 0.01), and biologic use (SHR 0.71, P < 0.01) were significantly associated with longer times to therapy adjustment. African American race (hazard ratio [HR] 0.63, P = 0.01), higher baseline disease activity (HR 0.75, P < 0.01), and not adjusting DMARD therapy within 90 days (HR 0.76, P = 0.01) were associated with longer times to LDAS.

Conclusion

Adjusting DMARDs within 90 days was associated with shorter times to LDAS, but many patients with persistent MHDAS waited >90 days to adjust DMARDs. Interventions are needed to address the timeliness of DMARD adjustments for RA patients with MHDAS.

     

Evaluation of a Methodologic Approach to Define an Inception Cohort of Rheumatoid Arthritis Patients Using Administrative Data

Objective

Identifying incident rheumatoid arthritis (RA) is desirable in order to create inception cohorts. We evaluated an approach to identify incident RA in health plan claims data.

Methods

Both Medicare and commercial claims data were linked to Corrona, a US RA registry. We evaluated the accuracy of year of RA onset in the registry (gold standard) versus different claims algorithms, varying International Classification of Diseases, Ninth Revision codes for RA/arthritis, duration of health plan enrollment preceding diagnosis (minimum of 1 versus 2 years), and use of RA medications. Results were reported as positive predictive values (PPVs) of the claims‐based algorithm for incident RA.

Results

Depending on the algorithm tested and whether patients were enrolled in Medicare or the commercial health plan, the PPVs for incident RA ranged from 68–81%. A 2‐year clean period free of all RA‐related diagnoses and medications was somewhat more optimal although, by comparison, a 1‐year clean period yielded similar PPVs and retained approximately 90% more RA patients for analysis.

Conclusion

Claims‐based algorithms can accurately identify incident RA.

     

Effect of Fatigue,Older Age,Higher Body Mass Index,and Female Sex on Disability in Early Rheumatoid Arthritis in the Treatment‐to‐Target Era

Objective

To compare disease activity and disability over 2 years in early rheumatoid arthritis (RA) before and after implementation of treat‐to‐target therapy and identify predictors of adverse outcome.

Methods

The Yorkshire Early Arthritis Register (YEAR) recruited 725 patients with early RA between 2002 and 2009, treated with a step‐up approach. The Inflammatory Arthritis Continuum study (IACON) recruited cases between 2010 and 2014 and treated to target. A total of 384 IACON cases met 2010 American College of Rheumatology/European League Against Rheumatism criteria. Latent growth curves of change in Disease Activity Score in 28 joints (DAS28) and the Health Assessment Questionnaire (HAQ) were compared between YEAR and IACON. Latent class growth analysis identified trajectories of change. Baseline predictors of trajectories were identified using logistic regression.

Results

The mean DAS28 over 2 years was lower in IACON than in YEAR. Latent trajectories of HAQ change in YEAR were high stable (21% of cohort), moderate reducing (35%), and low reducing (44%). Only moderate reducing (66%) and low reducing (34%) were seen in IACON. In both cohorts, female sex and fatigue predicted adverse HAQ trajectories (high stable and moderate reducing). Odds ratios (ORs) for moderate reducing compared to low reducing for women were 2.58 (95% confidence interval [95% CI] 1.69, 4.49) in YEAR and 5.81 (95% CI 2.44, 14.29) in IACON. ORs per centimeter fatigue visual analog score were 1.13 (95% CI 1.07, 1.20) in YEAR and 1.16 (95% CI 1.12, 1.20) in IACON.

Conclusion

Treat‐to‐target therapy gave more favorable trajectories of change in DAS28 and HAQ, but adverse HAQ trajectory was more likely in women with greater fatigue, suggesting such patients would benefit from interventions to improve function as well as reduce inflammation.

     

Pain Catastrophizing,Subjective Outcomes,and Inflammatory Assessments Including Ultrasound: Results From a Longitudinal Study of Rheumatoid Arthritis Patients

Objective

Pain catastrophizing is conceptualized as a negative cognitive–affective response to anticipated or actual pain and has been associated with important pain‐related outcomes. The objective of this prospective study of established rheumatoid arthritis (RA) patients was to explore how pain catastrophizing was related to patient‐reported outcomes (PROs), composite scores, and assessments of inflammatory activity.

Methods

RA patients starting biologic disease‐modifying antirheumatic drugs were examined at baseline and after 1, 2, 3, 6, and 12 months with PROs (joint pain/patient's global visual analog scale [VAS], modified Health Assessment Questionnaire, Rheumatoid Arthritis Impact of Disease score), clinical and laboratory assessments (tender/swollen joint count, assessor's global VAS, erythrocyte sedimentation rate/C‐reactive protein [CRP] level), ultrasound (US) (gray scale [GS]/power Doppler [PD] of 36 joints and 4 tendons), and pain catastrophizing. The composite scores for Disease Activity Score in 28 joints, Clinical Disease Activity Index, and Simplified Disease Activity Index were calculated. Statistical calculations included independent samples t‐test, paired samples t‐test, one‐way analysis of variance, Pearson's correlations, and linear and logistic regression.

Results

Of 209 patients included, 152 (72.7%) completed 12‐month followup. Pain catastrophizing, PROs, and clinical and inflammatory assessments decreased significantly (P < 0.001). Pain catastrophizing was strongly correlated with the PROs and composite scores (P < 0.001) but not with the inflammatory parameters (swollen joint count, CRP level, and GS/PD US). Patients with higher levels of pain catastrophizing had higher PROs and composite scores during the study (P < 0.001) but not inflammatory assessments. Baseline pain catastrophizing was negatively associated with achievement of remission at 6 and 12 months (P < 0.05).

Conclusion

Pain catastrophizing was strongly associated with PROs and composite measures, but not with markers of inflammation. High levels of pain catastrophizing reduced the likelihood of achieving composite score remission and should be a factor to consider in a treat‐to‐target strategy.

     

Occupation and Risk of Developing Rheumatoid Arthritis: Results From a Population‐Based Case–Control Study

Objective

Environmental factors are of importance for the etiology of rheumatoid arthritis (RA), but much remains unknown concerning the contributions from distinct occupational hazards. We explored the association between occupation and the risk of anti–citrullinated protein antibody (ACPA)+ RA or ACPA? RA.

Methods

We analyzed 3,522 cases and 5,580 controls from the Swedish population–based Epidemiological Investigation of Rheumatoid Arthritis case–control study. A questionnaire was used to obtain information on work history and lifestyle factors. Blood samples were drawn for serologic analyses. Unconditional logistic regression was used to calculate the odds ratio (OR) of RA associated with the last occupation before study inclusion. Analyses were performed with adjustments for known environmental exposures and lifestyle factors, including pack‐years of cigarette smoking, alcohol use, body mass index, and education.

Results

Among men, bricklayers and concrete workers (OR 2.9, 95% confidence interval [95% CI] 1.4–5.7), material handling operators (OR 2.4, 95% CI 1.3–4.4), and electrical and electronics workers (OR 2.1, 95% CI 1.1–3.8) had an increased risk of ACPA+ RA. For ACPA? RA, bricklayers and concrete workers (OR 2.4, 95% CI 1.0–5.7) and electrical and electronics workers (OR 2.6, 95% CI 1.3–5.0) had an increased risk. Among women, assistant nurses and attendants had a moderately increased risk of ACPA+ RA (OR 1.3, 95% CI 1.1–1.6). No occupations were significantly associated with ACPA? RA among women.

Conclusion

Mainly occupations related to potential noxious airborne agents were associated with an increased risk of ACPA+ or ACPA? RA, after adjustments for previously known confounders.

     

Determining the Risk Factors and Clinical Features Associated With Severe Gastrointestinal Dysmotility in Systemic Sclerosis

Objective

A subset of patients with systemic sclerosis (SSc) develop severe gastrointestinal (GI) dysmotility. We sought to determine predictors of severe SSc GI dysmotility and to identify distinct features associated with this phenotype.

Methods

Patients with SSc who required supplemental nutrition (enteral or parenteral tube feeding) were compared to SSc patients with mild GI symptoms in a cross‐sectional analysis. The association between severe GI dysmotility and clinical and serologic features was examined using logistic regression. Baseline data were examined to determine predictors of developing severe GI dysfunction using Cox regression.

Results

SSc patients with severe GI dysmotility (n = 66) were more likely than those patients with mild GI symptoms (n = 1,736) to be male (odds ratio [OR] 2.47 [95% confidence interval (95% CI) 1.34–4.56]; P = 0.004), and to have myopathy (OR 5.53 [95% CI 2.82–10.82]; P < 0.001), and sicca symptoms (OR 2.40 [95% CI 1.30–4.42]; P = 0.005), even after adjustment for potential confounders. Baseline features that were associated with the future development of severe GI dysfunction included male sex (hazard ratio [HR] 2.99 [95% CI 1.53–5.84]; P = 0.001) and myopathy (HR 5.08 [95% CI 2.21–11.67]; P < 0.001).

Conclusion

Distinct clinical features are present in SSc patients who are at risk of developing severe GI dysmotility. This finding is not only important clinically but also suggests that a unique pathologic process is at work in these patients.

     

Association of High Mobility Group Box Chromosomal Protein 1 and Receptor for Advanced Glycation End Products Serum Concentrations With Extraglandular Involvement and Disease Activity in Sjögren's Syndrome

Objective

To assess serum levels of high mobility group box chromosomal protein 1 (HMGB‐1) and the soluble receptor for advanced glycation end products (sRAGE) in patients with Sjögren's syndrome (SS) and explore correlations with disease activity.

Methods

Thirty‐nine patients with SS and 21 healthy controls were included in this cross‐sectional study. Clinical and laboratory values were obtained from all patients. Disease activity was assessed using the European League Against Rheumatism SS Disease Activity Index (ESSDAI). Serum samples were collected and HMGB‐1 and sRAGE levels were measured using enzyme‐linked immunosorbent assay (ELISA), and HMGB‐1 concentrations were semiquantified by Western blotting.

Results

In ELISA, HMGB‐1 serum levels did not differ between healthy controls and patients with SS (P = 0.783). When measured by semiquantitative Western blotting, HMGB‐1 levels were increased in patients with SS compared to healthy controls (P = 0.012). HMGB‐1 serum levels detected by Western blotting were higher in patients with extraglandular manifestations (P = 0.003) and were correlated with ESSDAI disease activity (r = 0.544, P < 0.0001). Furthermore, sRAGE was elevated in the sera of patients with SS (P = 0.003) compared to healthy controls and was also correlated with the ESSDAI (r = 0.545, P = 0.002).

Conclusion

Serum levels of total HMGB‐1 and sRAGE were elevated in patients with SS compared to healthy controls and correlated with disease activity as measured by the ESSDAI. Patients with extraglandular involvement had high serum levels of HMGB‐1.

     

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.

     

Disclosure of Personalized Rheumatoid Arthritis Risk Using Genetics,Biomarkers, and Lifestyle Factors to Motivate Health Behavior Improvements: A Randomized Controlled Trial

Objective

To determine the effect of disclosure of rheumatoid arthritis (RA) risk personalized with genetics, biomarkers, and lifestyle factors on health behavior intentions.

Methods

We performed a randomized controlled trial among first‐degree relatives without RA. Subjects assigned to the Personalized Risk Estimator for Rheumatoid Arthritis (PRE‐RA) group received the web‐based PRE‐RA tool for RA risk factor education and disclosure of personalized RA risk estimates, including genotype/autoantibody results and behaviors (n = 158). Subjects assigned to the comparison arm received standard RA education (n = 80). The primary outcome was readiness for change based on the trans‐theoretical model, using validated contemplation ladder scales. Increased motivation to improve RA risk–related behaviors (smoking, diet, exercise, or dental hygiene) was defined as an increase in any ladder score compared to baseline, assessed immediately, 6 weeks, and 6 months post‐intervention. Subjects reported behavior change at each visit. We performed intent‐to‐treat analyses using generalized estimating equations for the binary outcome.

Results

Subjects randomized to PRE‐RA were more likely to increase ladder scores over post‐intervention assessments (relative risk 1.23, 95% confidence interval [95% CI] 1.01, 1.51) than those randomized to nonpersonalized education. At 6 months, 63.9% of PRE‐RA subjects and 50.0% of comparison subjects increased motivation to improve behaviors (age‐adjusted difference 15.8%; 95% CI 2.8%, 28.8%). Compared to nonpersonalized education, more PRE‐RA subjects increased fish intake (45.0% versus 22.1%; P = 0.005), brushed more frequently (40.7% versus 22.9%; P = 0.01), flossed more frequently (55.7% versus 34.8%; P = 0.004), and quit smoking (62.5% versus 0.0% among 11 smokers; P = 0.18).

Conclusion

Disclosure of RA risk personalized with genotype/biomarker results and behaviors increased motivation to improve RA risk–related behaviors. Personalized medicine approaches may motivate health behavior improvements for those at risk for RA and provide rationale for larger studies evaluating effects of behavior changes on clinical outcomes, such as RA‐related autoantibody production or RA development.

     

Relationship Between Knee Pain and Infrapatellar Fat Pad Morphology: A Within‐ and Between‐Person Analysis From the Osteoarthritis Initiative

Objective

Inflammation is known to be strongly associated with knee pain in osteoarthritis. The infrapatellar fat pad represents a potential source of proinflammatory cytokines. Yet the relationship between infrapatellar fat pad morphology and osteoarthritis symptoms is unclear.

Methods

Here we investigate quantitative imaging parameters of infrapatellar fat pad morphology between painful versus contralateral pain‐free legs of subjects with unilateral knee pain and patients with chronic knee pain versus those of matched pain‐free control subjects. A total of 46 subjects with strictly unilateral frequent knee pain and bilateral radiographic osteoarthritis (Kellgren/Lawrence grade 2/3) were drawn from the Osteoarthritis Initiative. Further, 43 subjects with chronic knee pain over 4 years and 43 matched pain‐free controls without pain over this period were studied. Infrapatellar fat pad morphology (volume, surface area, and depth) was determined by manual segmentation of sagittal magnetic resonance images.

Results

No significant differences in infrapatellar fat pad morphology were observed between painful versus painless knees of persons with strictly unilateral knee pain (mean difference ?0.7% (95% confidence interval [95% CI] ?0.6, 0.9; P = 0.64) or between chronically painful knees versus matched painless controls (?2.1% [95% CI ?2.2, 1.1]; P = 0.51).

Conclusion

Independent of the ambiguous role of the infrapatellar fat pad in knee osteoarthritis (a potential source of proinflammatory cytokines or a mechanical shock absorber), the size of the infrapatellar fat pad does not appear to be related to knee pain.

     

Development and Pilot Testing of Multimedia Patient Education Tools for Patients With Knee Osteoarthritis,Osteoporosis, and Rheumatoid Arthritis

Objective

We developed and tested multimedia patient education tools (video tools) for patients with knee osteoarthritis (OA), osteoporosis (OP), and rheumatoid arthritis (RA).

Methods

We followed an “edutainment” model, incorporating educational patient story lines. The goals were designed to make the programs both didactic and entertaining, with navigation and graphic user interfaces as simple as possible. We created both English and Spanish language versions. Once the video tool was finalized, 60 patients, 20 per disease, were shown the tool and interviewed. Disease knowledge was our primary outcome, and decision conflict, disease management, and acceptability were secondary outcomes.

Results

We observed statistically significant differences in pre‐ to postintervention knowledge questionnaire scores (before and after viewing the video tool) (OA: P = 0.03, OP: P = 0.01, and RA: P < 0.0001). Most participants felt they gained “clarity” on disease duration, symptoms, and the time medication takes to start acting; were “encouraged to see their doctor regularly”; and were more aware about taking their medications. In terms of acceptability, most patients in all disease groups found the length and amount of information presented in the video tools to be “just right,” and the presentation to be “balanced.” In terms of comprehension, all participants provided a favorable evaluation of the video tool; all found the video easy to use, the vocabulary easy to understand, and the materials to be well organized.

Conclusion

Multimedia tools that incorporate videos may help patients better understand and manage their disease. Patient involvement in the development process is essential to ensure relevant content and usability.

     

Morphology of the Toe Flexor Muscles in Older Adults With Toe Deformities

Objective

It has been suggested that atrophied or weak toe flexor muscles are associated with the formation of toe deformities, but there is little evidence to support this theory. This study aimed to determine whether the size of the toe flexor muscles differed in older adults with and without toe deformities.

Methods

Forty‐four older adults (>60 years) were recruited for the study. Each participant had their feet assessed for the presence of hallux valgus or lesser toe deformities. Intrinsic and extrinsic toe flexor muscles were imaged with an ultrasound system using a standardized protocol. Assessor‐blinded measurements of muscle thickness and cross‐sectional area were taken using Image J software.

Results

Participants with lesser toe deformities (n = 20) were found to have significantly smaller quadratus plantae (P = 0.003), flexor digitorum brevis (P = 0.013), abductor hallucis (P = 0.004), and flexor hallucis brevis (P = 0.005) muscles than the participants without any toe deformities (n = 19). Female participants with hallux valgus (n = 10) were found to have significantly smaller abductor hallucis (P = 0.048) and flexor hallucis brevis (P = 0.013) muscles than the female participants without any toe deformities (n = 10; P < 0.05).

Conclusion

This is the first study to use ultrasound to investigate the size of the toe flexor muscles in older adults with hallux valgus and lesser toe deformities compared to otherwise healthy older adults. The sizes of the abductor hallucis and flexor hallucis brevis muscles were decreased in participants with hallux valgus, whereas the quadratus plantae, flexor digitorum brevis, abductor hallucis, and flexor hallucis brevis muscles were smaller in the participants with lesser toe deformities.

     

Effect of Comprehensive Behavioral and Exercise Intervention on Physical Function and Activity Participation After Total Knee Replacement: A Pilot Randomized Study

Objective

To test the feasibility of a comprehensive behavioral intervention (CBI) program that combines intense exercises with an education program, to be implemented at a later stage (3 months) following total knee replacement (TKR), and to get a first impression of the effects of the CBI as compared to a standard of care exercise (SCE) program on the outcomes of physical function and physical activity.

Methods

A total of 44 subjects participated in a 3‐month program of either CBI or SCE, followed by 3 months of a home exercise program. Outcomes of physical function and physical activity were measured at baseline and at 6‐month followup. Analysis of variance was used to compare statistical differences between groups, whereas responder analyses were used for clinically important differences.

Results

The CBI was found to be safe and well tolerated. As compared to the SCE group, the CBI group had less pain (P = 0.035) and better physical function based on the Short Form 36 health survey (P = 0.017) and the single‐leg stance test (P = 0.037). The other outcome measures did not demonstrate statistically significant differences between the 2 groups. Results from the responder analysis demonstrated that the CBI group had a 36% higher rate of responders in physical function as compared to the SCE group. Also, the CBI group had 23% more responders in the combined domains of physical function and physical activity.

Conclusion

The CBI program is feasible and improves physical function and physical activity in patients several months after TKR. Larger pragmatic randomized trials are needed to confirm the results of this study.

     

Nationwide Experience With Off‐Label Use of Interleukin‐1 Targeting Treatment in Familial Mediterranean Fever Patients

Objective

Approximately 30–45% of patients with familial Mediterranean fever (FMF) have been reported to have attacks despite colchicine treatment. Currently, data on the treatment of colchicine‐unresponsive or colchicine‐intolerant FMF patients are limited; the most promising alternatives seem to be anti–interleukin‐1 (anti–IL‐1) agents. Here we report our experience with the off‐label use of anti–IL‐1 agents in a large group of FMF patients.

Methods

In all, 21 centers from different geographical regions of Turkey were included in the current study. The medical records of all FMF patients who had used anti–IL‐1 treatment for at least 6 months were reviewed.

Results

In total, 172 FMF patients (83 [48%] female, mean age 36.2 years [range 18–68]) were included in the analysis; mean age at symptom onset was 12.6 years (range 1–48), and the mean colchicine dose was 1.7 mg/day (range 0.5–4.0). Of these patients, 151 were treated with anakinra and 21 with canakinumab. Anti–IL‐1 treatment was used because of colchicine‐resistant disease in 84% and amyloidosis in 12% of subjects. During the mean 19.6 months of treatment (range 6–98), the yearly attack frequency was significantly reduced (from 16.8 to 2.4; P < 0.001), and 42.1% of colchicine‐resistant FMF patients were attack free. Serum levels of C‐reactive protein, erythrocyte sedimentation rate, and 24‐hour urinary protein excretion (5,458.7 mg/24 hours before and 3,557.3 mg/24 hours after) were significantly reduced.

Conclusion

Anti–IL‐1 treatment is an effective alternative for controlling attacks and decreasing proteinuria in colchicine‐resistant FMF patients.

     

Impact of Obesity and Adiposity on Inflammatory Markers in Patients With Rheumatoid Arthritis

Objective

The C‐reactive protein (CRP ) level and erythrocyte sedimentation rate (ESR ) are important disease activity biomarkers in rheumatoid arthritis (RA ). This study aimed to determine to what extent obesity biases these biomarkers.

Methods

Body mass index (BMI ) associations with CRP level and ESR were assessed in 2 RA cohorts: the cross‐sectional Body Composition (BC ) cohort (n = 451), including whole‐body dual x‐ray absorptiometry measures of fat mass index; and the longitudinal Veterans Affairs Rheumatoid Arthritis (VARA ) registry (n = 1,652), using multivariable models stratified by sex. For comparison, associations were evaluated in the general population using the National Health and Nutrition Examination Survey.

Results

Among women with RA and in the general population, greater BMI was associated with greater CRP levels, especially among women with severe obesity (P < 0.001 for BMI ≥35 kg/m² versus 20–25 kg/m²). This association remained after adjustment for joint counts and patient global health scores (P < 0.001 in BC and P < 0.01 in VARA ), but was attenuated after adjustment for fat mass index (P = 0.17). Positive associations between BMI and ESR in women were more modest. In men with RA , lower BMI was associated with higher CRP levels and ESR , contrasting with positive associations among men in the general population.

Conclusion

Obesity is associated with higher CRP levels and ESR in women with RA . This association is related to fat mass and not RA disease activity. Low BMI is associated with higher CRP levels in men with RA ; this unexpected finding remains incompletely explained but likely is not a direct effect of adiposity.