Disease control and health‐related quality of life in juvenile idiopathic arthritis

Objective

To examine variability in health‐related quality of life (HRQOL) in children with juvenile idiopathic arthritis (JIA) experiencing no or minimal clinical symptoms, and in a subgroup with polyarticular JIA treated with biologic agents for 12 months.

Methods

We defined 3 samples using a database of patients ages 2–18 years with JIA (n = 524; patient visits [PV] = 2,354): visits (PV = 2,155) with no or minimal clinical symptoms on at least 1 of 4 measures (active joint count, pain, physician global disease rating, Childhood Health Assessment Questionnaire); visits (PV = 941) with no or minimal symptoms on all 4 measures; and children (n = 31) with polyarticular JIA treated with biologic agents for 12 months. HRQOL was measured using the Pediatric Quality of Life Inventory (PedsQL) and the percentage of patients with suboptimal HRQOL was determined.

Results

In PV with a PedsQL score, suboptimal HRQOL by self‐report occurred in 362 (20.6%) PV with at least 1 indicator of minimal symptoms, and in 64 (7.9%) PV with all 4 measures indicating minimal symptoms (519 [25.7%] and 95 [10.7%], respectively, by parent report). For children with polyarticular JIA treated for 12 months with biologic agents, 7 (25.9%) patients by self‐report and 10 (35.7%) patients by parent report were in the suboptimal range of HRQOL.

Conclusion

A substantial percentage of patients with JIA who report no or mild clinical symptoms experience suboptimal HRQOL. This is also true for patients with polyarticular JIA treated with biologic agents for 12 months. Although disease activity and clinical symptoms are related to HRQOL, considerable unexplained variation in HRQOL exists. HRQOL needs to be assessed independently regardless of clinical status.

     

Safety of the selective costimulation modulator abatacept in rheumatoid arthritis patients receiving background biologic and nonbiologic disease‐modifying antirheumatic drugs: A one‐year randomized,placebo‐controlled study

Objective

To assess the safety of abatacept, a selective costimulation modulator, in patients with active rheumatoid arthritis (RA) who had been receiving ≥1 traditional nonbiologic and/or biologic disease‐modifying antirheumatic drugs (DMARDs) approved for the treatment of RA for at least 3 months prior to entry into the study.

Methods

This was a 1‐year, multicenter, randomized, double‐blind, placebo‐controlled trial. Patients were randomized 2:1 to receive abatacept at a fixed dose approximating 10 mg/kg by weight range, or placebo.

Results

The abatacept and placebo groups exhibited similar frequencies of adverse events (90% and 87%, respectively), serious adverse events (13% and 12%, respectively), and discontinuations due to adverse events (5% and 4%, respectively). Five patients (0.5%) in the abatacept group and 4 patients (0.8%) in the placebo group died during the study. Serious infections were more frequent in the abatacept group than in the placebo group (2.9% versus 1.9%). Fewer than 4% of patients in either group experienced a severe or very severe infection. The incidence of neoplasms was 3.5% in both groups. When evaluated according to background therapy, serious adverse events occurred more frequently in the subgroup receiving abatacept plus a biologic agent (22.3%) than in the other subgroups (11.7–12.5%).

Conclusion

Abatacept in combination with synthetic DMARDs was well tolerated and improved physical function and physician‐ and patient‐reported disease outcomes. However, abatacept in combination with biologic background therapies was associated with an increase in the rate of serious adverse events. Therefore, abatacept is not recommended for use in combination with biologic therapy.

     

Abatacept in the treatment of patients with psoriatic arthritis: Results of a six‐month,multicenter, randomized,double‐blind,placebo‐controlled,phase II trial

Objective

To assess the safety and efficacy of abatacept, a selective T cell costimulation modulator, in patients with psoriatic arthritis (PsA).

Methods

In this 6‐month, multicenter, randomized, double‐blind, placebo‐controlled, phase II study, 170 PsA patients with a psoriasis target lesion (TL) ≥2 cm who had previously taken disease‐modifying antirheumatic drugs (DMARDs), including anti–tumor necrosis factor (anti‐TNF) agents, were randomized (1:1:1:1) to receive placebo or abatacept at doses of 3 mg/kg, 10 mg/kg, or 30/10 mg/kg (2 initial doses of 30 mg/kg, followed by 10 mg/kg) on days 1, 15, and 29 and then once every 28 days thereafter. The primary end point was the American College of Rheumatology 20% criteria for improvement (ACR20 response) on day 169. Other key end points were magnetic resonance imaging (MRI) scores for joint erosion, osteitis, and synovitis, scores on the Health Assessment Questionnaire (HAQ) and the Short Form‐36 (SF‐36) health survey, the investigator's global assessment of psoriasis, the TL score, and the Psoriasis Area and Severity Index (PASI) score.

Results

Proportions of patients achieving an ACR20 response were 19%, 33%, 48%, and 42% in the placebo, the abatacept 3 mg/kg, the abatacept 10 mg/kg, and the abatacept 30/10 mg/kg groups, respectively. Compared with placebo, improvements were significantly higher for the abatacept 10 mg/kg (P = 0.006) and 30/10 mg/kg (P = 0.022) groups, but not for 3 mg/kg group (P = 0.121). All abatacept regimens resulted in improved MRI, HAQ, and SF‐36 scores, with 10 mg/kg showing the greatest improvements. Improvements in the TL and PASI scores were observed in all abatacept arms; a response according to the investigator's global assessment was seen only with 3 mg/kg of abatacept. The safety profiles were similar among the treatment arms.

Conclusion

The results of this study suggest that 10 mg/kg of abatacept, the approved dosage for rheumatoid arthritis and juvenile idiopathic arthritis, may be an effective treatment option for PsA.

     

Health‐related quality of life in adolescents with juvenile idiopathic arthritis

Objective

To describe the health‐related quality of life (HRQOL) of adolescents with juvenile idiopathic arthritis (JIA), and to examine the usefulness of the Juvenile Arthritis Quality of Life Questionnaire (JAQQ) in a UK context. It was hypothesized that HRQOL would decrease with worsening disease and disability.

Methods

Patients with JIA ages 11, 14, and 17 years were recruited from 10 major rheumatology centers. HRQOL was measured using the JAQQ. Other data were core outcome variables including the Childhood Health Assessment Questionnaire, demographic characteristics, arthritis‐related knowledge, and satisfaction with health care.

Results

Questionnaires were completed by 308 adolescents. One‐fifth had persistent oligoarthritis. Median disease duration was 5.7 years (range <1–16 years). The JAQQ was shown to have good psychometric properties when used in the UK, but was not without limitations. HRQOL of adolescents with JIA was less than optimal, particularly in the domains of gross motor and systemic functioning. Items most frequently rated as adolescents' biggest psychological problems were “felt frustrated” and “felt depressed,” rated by 30.2% and 23.4%, respectively. These were particularly problematic for the 17‐year‐olds, with 39% reporting frustration as one of their biggest problems and 63.6% reporting depression. Variation in the adolescent JAQQ scores was explained by functional disability, pain, and disease activity.

Conclusion

JIA can have a significant adverse effect on the HRQOL of adolescents. The JAQQ is a useful tool to assess the HRQOL of UK adolescents with JIA, but there is need for improved measures that incorporate developmentally appropriate issues.

     

A randomized,placebo‐controlled,double‐masked clinical trial of etanercept for the treatment of uveitis associated with juvenile idiopathic arthritis

Objective

To investigate the safety and efficacy of etanercept in the treatment of uveitis associated with juvenile idiopathic arthritis (JIA).

Methods

Children who met the American College of Rheumatology diagnostic criteria for JIA with active uveitis, who had anterior chamber cells of ≥1+ or requiring topical corticosteroid ≥3 times daily, and who were on a stable regimen for arthritis treatment were eligible. Study participants received etanercept (0.4 mg/kg) or placebo administered subcutaneously twice weekly for 6 months. All participants received open‐label etanercept for an additional 6 months.

Results

Five patients received placebo and 7 received etanercept. Three of the 7 patients treated with etanercept and 2 of the 5 placebo‐treated patients were considered ophthalmic successes (P = 1.0). One patient in each treatment group was considered a treatment failure. Three of the 7 etanercept‐treated and 2 of the 5 placebo‐treated patients were neither successes nor failures by our definition. There were no serious adverse events for any patient during the entire study period. Reports of minor infections were comparable in each treatment group, 71% for etanercept and 60% for placebo (P = 0.58).

Conclusion

In this small pilot study there was no apparent difference in the anterior segment inflammation between patients treated with etanercept and placebo. The stringent criteria used to measure ophthalmic success of treatment and the small patient population limit the implications of our findings.

     

Psoriasis predicts a poor short‐term outcome in patients with spondylarthropathy

Objective

The outcome of patients with recent‐onset spondylarthropathy (SpA) is unclear. Therefore, the objective of this study was to prospectively correlate clinical and laboratory features with functional and radiologic outcome in patients with psoriatic SpA (PsS), undifferentiated SpA (uSpA), and Reiter's syndrome/reactive arthritis (ReA).

Methods

Patients presenting to an early arthritis clinic with a spondylarthropathy pattern of peripheral arthritis were selected and prospectively followed. Clinical and laboratory features were recorded at baseline, 12 months, and 24 months. Radiographs of affected joints were taken at presentation and at followup.

Results

The cohort consisted of 157 patients: 82 PsS, 59 uSpA, and 16 ReA. Symptom duration at presentation was progressively shorter, and the erythrocyte sedimentation rate/C‐reactive protein (ESR/CRP) incrementally higher in ReA, uSpA, and PsS, respectively. There was a higher swollen joint count (SJC) in PsS compared with uSpA. In PsS, strong positive correlations were observed between ESR/CRP and articular indices. Initially, functional impairment was greater in ReA compared with uSpA and PsS but resolved completely in ReA. Clinical remission rates at 2 years were ReA 61% and uSpA 63%, compared with PsS 14%. Remission at 2 years could be predicted in SpA by disease category and presentation SJC. Baseline erosions in PsS (28%) and uSpA (5%) increased to 45% and 25%, respectively, at 2 years.

Conclusion

These observations suggest a spectrum within the spondylarthropathy subgroups where at presentation the acute phase markers in ReA and uSpA reflect a systemic process, whereas in PsS they reflect articular manifestations. Although the clinical presentations are indistinguishable, PsS has a more aggressive clinical course with a poorer functional and radiologic outcome.

     

The efficacy and safety of abatacept in patients with non–life‐threatening manifestations of systemic lupus erythematosus: Results of a twelve‐month,multicenter, exploratory,phase IIb,randomized, double‐blind,placebo‐controlled trial

Objective

To evaluate abatacept therapy in patients with non–life‐threatening systemic lupus erythematosus (SLE) and polyarthritis, discoid lesions, or pleuritis and/or pericarditis.

Methods

In a 12‐month, multicenter, exploratory, phase IIb randomized, double‐blind, placebo‐controlled trial, SLE patients with polyarthritis, discoid lesions, or pleuritis and/or pericarditis were randomized at a ratio of 2:1 to receive abatacept (∼10 mg/kg of body weight) or placebo. Prednisone (30 mg/day or equivalent) was given for 1 month, and then the dosage was tapered. The primary end point was the proportion of patients with new flare (adjudicated) according to a score of A/B on the British Isles Lupus Assessment Group (BILAG) index after the start of the steroid taper.

Results

A total of 118 patients were randomized to receive abatacept and 57 to receive placebo. The baseline characteristics were similar in the 2 groups. The proportion of new BILAG A/B flares over 12 months was 79.7% (95% confidence interval [95% CI] 72.4, 86.9) in the abatacept group and 82.5% (95% CI 72.6, 92.3) in the placebo group (treatment difference −3.5 [95% CI −15.3, 8.3]). Other prespecified flare end points were not met. In post hoc analyses, the proportions of abatacept‐treated and placebo‐treated patients with a BILAG A flare were 40.7% (95% CI 31.8, 49.5) versus 54.4% (95% CI 41.5, 67.3), and the proportions with physician‐assessed flare were 63.6% (95% CI 54.9, 72.2) and 82.5% (95% CI 72.6, 92.3), respectively; treatment differences were greatest in the polyarthritis group. Prespecified exploratory patient‐reported outcomes (Short Form 36 health survey, sleep problems, fatigue) demonstrated a treatment effect with abatacept. The frequency of adverse events (AEs) was comparable in the abatacept and placebo groups (90.9% versus 91.5%), but serious AEs (SAEs) were higher in the abatacept group (19.8 versus 6.8%). Most SAEs were single, disease‐related events occurring during the first 6 months of the study (including the steroid taper period).

Conclusion

Although the primary/secondary end points were not met in this study, improvements in certain exploratory measures suggest some abatacept efficacy in patients with non–life‐threatening manifestations of SLE. The increased rate of SAEs requires further assessment.

     

Impact of fatigue on health‐related quality of life in rheumatoid arthritis

Objective

To multidimensionally assess fatigue in rheumatoid arthritis (RA) and to evaluate the impact of fatigue on health‐related quality of life (HRQOL).

Methods

The study was conducted in 1999 among 490 RA patients with varying disease duration. Fatigue was measured with the Multidimensional Fatigue Inventory (MFI‐20) and HRQOL with a validated Dutch version of the RAND 36‐Item Health Survey. We evaluated the impact of fatigue on HRQOL by multiple linear regression analyses taking into account RA‐related pain and depressive symptoms.

Results

Different aspects of fatigue selectively explained different dimensions of HRQOL. The MFI‐20 was entered last to the linear regression models, resulting in an additional increase of explained variance of 1% (mental health) to 14% (vitality).

Conclusion

The multidimensional portrayal of RA‐related fatigue can be used to develop intervention strategies targeted to specific aspects of fatigue. Fatigue, supplementary to RA‐related pain and depressive symptoms, appears to be a feasible and treatable target in the clinical management of RA to increase HRQOL.

     

Treatment of rheumatoid arthritis with the selective costimulation modulator abatacept: Twelve‐month results of a phase iib,double‐blind,randomized, placebo‐controlled trial

Objective

To determine the clinical efficacy, safety, and immunogenicity of abatacept (CTLA‐4Ig), a selective costimulation modulator, in patients with rheumatoid arthritis (RA) that has remained active despite methotrexate (MTX) therapy.

Methods

This was a 12‐month, multicenter, randomized, double‐blind, placebo‐controlled study. A total of 339 patients with active RA despite MTX therapy were randomly assigned to receive 10 mg/kg abatacept (n = 115), 2 mg/kg abatacept (n = 105), or placebo (n = 119). This report focuses on the results observed at month 12 of a phase IIb trial.

Results

A significantly greater percentage of patients treated with 10 mg/kg abatacept met the American College of Rheumatology 20% improvement criteria (achieved an ACR20 response) at 1 year compared with patients who received placebo (62.6% versus 36.1%; P < 0.001). Greater percentages of patients treated with 10 mg/kg abatacept also achieved ACR50 responses (41.7% versus 20.2%; P < 0.001) and ACR70 responses (20.9% versus 7.6%; P = 0.003) compared with patients who received placebo. For patients treated with 10 mg/kg abatacept, there were also statistically significant and clinically important improvements in modified Health Assessment Questionnaire scores compared with patients who received placebo (49.6% versus 27.7%; P < 0.001). Abatacept at a dosage of 10 mg/kg elicited an increase in rates of remission (Disease Activity Score in 28 joints of <2.6) compared with placebo at 1 year (34.8% versus 10.1%; P < 0.001). The incidence of adverse events was comparable between the groups, and no significant formation of neutralizing antibodies was noted.

Conclusion

Abatacept was associated with significant reductions in disease activity and improvements in physical function that were maintained over the course of 12 months in patients with RA that had remained active despite MTX treatment. Abatacept was found to be well tolerated and safe over the course of 1 year. Abatacept in combination with MTX has the potential to play an important role in future RA therapy.

     

Immunogenicity,Safety, and Efficacy of Abatacept Administered Subcutaneously With or Without Background Methotrexate in Patients With Rheumatoid Arthritis: Results From a Phase III,International, Multicenter,Parallel‐Arm,Open‐Label Study

Objective

To evaluate the impact of concomitant methotrexate (MTX) on subcutaneous (SC) abatacept immunogenicity, and to assess safety and efficacy.

Methods

This phase III, open‐label study had a 4‐month short‐term (ST) period and an ongoing long‐term extension (LTE) period. Rheumatoid arthritis patients were stratified to receive SC abatacept (125 mg/week) with (combination) or without MTX (monotherapy), with no intravenous loading dose; patients receiving monotherapy could add MTX in the LTE period. Immunogenicity (percentage of anti‐abatacept antibody–positive patients) was assessed. ST and LTE period data are reported, including efficacy through LTE month 14 and safety through LTE month 20.

Results

Ninety‐six of 100 enrolled patients completed the ST period; 3.9% (combination) and 4.1% of patients (monotherapy) developed transient immunogenicity, and no patients were antibody positive at month 4. Serious adverse events (SAEs) were reported in 3.9% (combination) and 6.1% of patients (monotherapy); 5.9% (combination) and 8.2% of patients (monotherapy) experienced SC injection reactions, and all were mild in intensity. Mean 28‐joint Disease Activity Score (DAS28) changes were ?1.67 (95% confidence interval [95% CI] ?2.06, ?1.28; combination) and ?1.94 (95% CI ?2.46, ?1.42; monotherapy) at month 4. Ninety patients entered and were treated in the LTE period; 83.3% (75 of 90) remained ongoing at month 24. One LTE‐treated patient (1.1%) developed immunogenicity, 14.4% of patients experienced SAEs, and no SC injection reactions were reported. For patients entering the LTE period, mean DAS28 changes from baseline were ?1.84 (95% CI ?2.23, ?1.34; combination) and ?2.86 (95% CI ?3.46, ?2.27; monotherapy) at month 18.

Conclusion

SC abatacept did not elicit immunogenicity associated with loss of safety or efficacy, either with or without MTX.

     

Feasibility and construct validity of the parent willingness‐to‐pay technique for children with juvenile idiopathic arthritis

Objective

To assess the feasibility and construct validity of the willingness‐to‐pay (WTP) technique for measuring health care preferences in families of children with juvenile idiopathic arthritis (JIA).

Methods

Parents were asked to estimate the monthly US dollar amount they would be willing to pay to obtain for their child the following hypothetical drugs: ARTHRO, which guarantees complete clinical response; and NO‐STOM‐ACHE, a drug that eliminates gastrointestinal (GI) symptoms. A yes/no question was used with random assignment of the starting bids. Parents who agreed to pay the starting bid were then asked whether they would be willing to pay 200% and then 400% of this initial bid. Socioeconomic data and information on medications, disease activity, patient physical function, wellbeing, and health‐related quality of life (HRQOL) were obtained.

Results

Sixty‐two families of children with JIA were interviewed. GI symptoms were present in 54%, and 53% of the children had joints with active arthritis or limited range of motion. Four parents (7%) were unwilling to pay anything for any of the studied medications. The mean amount (median; mean percentage of available family income) families were willing to pay was $395 ($300; 15%) for ARTHRO and $109 ($80; 4%) for NO‐STOM‐ACHE. Correlation and regression analysis supported that, adjusted for the available family income, the WTP for ARTHRO was associated with disease activity, pain, and the HRQOL of the patients. After correction for the starting bids and the available family income, the WTP for NO‐STOM‐ACHE was associated with the patient's HRQOL, pain, and the amount of GI discomfort.

Conclusion

The WTP technique is feasible and has construct validity for measuring health care preferences for children with JIA. Relatively large WTP estimates support a possible important negative impact of the disease on families of children with JIA.

     

Long‐term safety and efficacy of abatacept in children with juvenile idiopathic arthritis

Objective

We previously documented that abatacept was effective and safe in patients with juvenile idiopathic arthritis (JIA) who had not previously achieved a satisfactory clinical response with disease‐modifying antirheumatic drugs or tumor necrosis factor blockade. Here, we report results from the long‐term extension (LTE) phase of that study.

Methods

This report describes the long‐term, open‐label extension phase of a double‐blind, randomized, controlled withdrawal trial in 190 patients with JIA ages 6–17 years. Children were treated with 10 mg/kg abatacept administered intravenously every 4 weeks, with or without methotrexate. Efficacy results were based on data derived from the 153 patients who entered the open‐label LTE phase and reflect ≥21 months (589 days) of treatment. Safety results include all available open‐label data as of May 7, 2008.

Results

Of the 190 enrolled patients, 153 entered the LTE. By day 589, 90%, 88%, 75%, 57%, and 39% of patients treated with abatacept during the double‐blind and LTE phases achieved responses according to the American College of Rheumatology (ACR) Pediatric 30 (Pedi 30), Pedi 50, Pedi 70, Pedi 90, and Pedi 100 criteria for improvement, respectively. Similar response rates were observed by day 589 among patients previously treated with placebo. Among patients who had not achieved an ACR Pedi 30 response at the end of the open‐label lead‐in phase and who proceeded directly into the LTE, 73%, 64%, 46%, 18%, and 5% achieved ACR Pedi 30, Pedi 50, Pedi 70, Pedi 90, and Pedi 100 responses, respectively, by day 589 of the LTE. No cases of tuberculosis and no malignancies were reported during the LTE. Pneumonia developed in 3 patients, and multiple sclerosis developed in 1 patient.

Conclusion

Abatacept provided clinically significant and durable efficacy in patients with JIA, including those who did not initially achieve an ACR Pedi 30 response during the initial 4‐month open‐label lead‐in phase.

     

Performance of a generic health‐related quality of life measure in a clinic population with rheumatic disease

Objective

To assess the performance of a generic health‐related quality of life (HRQOL) measure in a rheumatology clinic population.

Methods

Participants (n = 619) with fibromyalgia, rheumatoid arthritis, or osteoarthritis receiving care from rheumatologists completed mailed questionnaires that included the Behavioral Risk Factor Surveillance System (BRFSS) HRQOL measure and condition‐specific measures assessing disability, pain, fatigue, and helplessness. The BRFSS assesses global health and number of days in the past 30 of poor physical or mental health or activity limitation. The overall sample was described, followed by comparison of adjusted scores on all HRQOL measures by diagnosis.

Results

Participants reported mild difficulty with activities of daily living, marked pain and fatigue, and moderate helplessness. Participants reported a mean of 8 or more days out of 30 of poor physical and mental health and activity limitations; more than 40% reported poor or fair health. Participants with fibromyalgia reported more ill health on condition‐specific measures and the BRFSS HRQOL measures than did participants with osteoarthritis or rheumatoid arthritis.

Conclusion

The BRFSS HRQOL measure is a brief, easily administered, generic health indicator that shows differences among rheumatic disease diagnoses.

     

Reductions in health‐related quality of life in patients with ankylosing spondylitis and improvements with etanercept therapy

Objective

To assess the impact of ankylosing spondylitis (AS) on patient health‐related quality of life (HRQOL) relative to both the general US and chronically‐ill populations, and to evaluate whether etanercept therapy can reverse impairments in HRQOL due to AS.

Methods

Two AS patient populations were evaluated: patients with AS from a US clinical trial who were randomized to receive either etanercept (n = 20) or placebo (n = 20) for 16 weeks, and placebo‐treated patients from a multinational sample who subsequently received etanercept (n = 129) during a 48‐week, open‐label extension study. A sample from the US general population and patients with other medical conditions derived from the National Survey of Functional Health Status were used as comparators to evaluate the relative impact of active AS on HRQOL, as measured by the Short Form 36 (SF‐36) questionnaire.

Results

At baseline, patients with AS in both the US and multinational samples had significantly lower scores than the US general population on all 8 SF‐36 scales. Compared with patients with other medical conditions, patients with AS had the lowest scores in the physical domains—Physical Functioning, Role Physical, and Bodily Pain. Impairments in SF‐36 scores for psychosocial domains, such as Social Functioning, Role Emotional, and Mental Health, were somewhat less pronounced in patients with AS. Treatment with etanercept significantly improved the HRQOL of patients with AS on all 8 SF‐36 scales, especially in the same physical domains that showed the greatest impairments prior to treatment (Physical Functioning, Role Physical, and Bodily Pain).

Conclusion

Patients with active AS despite conventional therapy have significantly reduced HRQOL across a wide range of domains. These reductions are most pronounced in the physical domains and exceed those seen in many other chronic diseases. Etanercept therapy significantly improves patient HRQOL, indicating that decrements in HRQOL due to AS may be at least partly reversible.

     

Prevalence,risk factors,and outcome of uveitis in juvenile idiopathic arthritis: A long‐term followup study

Objective

To assess the prevalence, risk factors, and long‐term outcome of uveitis in patients with juvenile idiopathic arthritis (JIA).

Methods

An inception cohort of all 1,081 patients diagnosed as having JIA at a single tertiary care center was established. A questionnaire and followup telephone calls were used to confirm the diagnosis of uveitis. Ophthalmologists' records of patients with uveitis were collected. Kaplan‐Meier and Cox regression analyses were used to assess risk factors for developing uveitis and for complications of uveitis.

Results

After a mean followup time of 6.9 years, 142 of 1,081 patients (13.1%) had developed uveitis. Risk factors were young age at diagnosis, female sex, antinuclear antibody positivity, and the subtype of JIA. The relative contribution of these risk factors was different for the different subtypes of JIA. Until the end of the study, uveitis complications had developed in 53 of 142 patients with uveitis (37.3%; 4.9% of the total cohort). Only 16 of 175 involved eyes (9.1%) in 14 of 108 patients (13%; 1.3% of the total cohort) for whom ophthalmology reports were available had best corrected visual acuity less than 20/40 (mean followup time for uveitis of 6.3 years). Abnormal vision was associated with synechiae or cataract.

Conclusion

Risk factors for developing uveitis were different among subtypes of JIA. The long‐term outcome of JIA‐associated uveitis in our cohort was excellent despite the high rate of complications.

     

Impact of fibromyalgia pain on health‐related quality of life before and after treatment with tramadol/acetaminophen

Objective

To assess health‐related quality of life (HRQOL) in patients with moderate‐to‐severe fibromyalgia pain compared with the general population, and to assess the relationship between pain severity and HRQOL before and after treatment with an analgesic.

Methods

Data were obtained from a randomized, double‐blind study of patients with moderate‐to‐severe fibromyalgia pain. Patients received either tramadol/acetaminophen or placebo 4 times/day as needed for 91 days. HRQOL was measured with the Short Form 36 Health Survey (SF‐36) and the Fibromyalgia Impact Questionnaire (FIQ). Baseline HRQOL scores were compared with a national sample of noninstitutionalized adults and a sample of patients with impaired HRQOL due to congestive heart failure. Patients with fibromyalgia were divided into tertiles by change in pain severity, and SF‐36 scores were compared across the tertiles. Mean changes in SF‐36 and FIQ scores were compared between treatment groups.

Results

Patients with fibromyalgia scored lower than the US norm on all SF‐36 scales (P < 0.0001) and lower than patients with congestive heart failure on most scales. More severe pain was associated with greater impairment of HRQOL compared with less severe pain (P < 0.0001). Patients in the highest tertile for improved pain severity had greater improvement in HRQOL scores than patients in the lower tertiles. Compared with patients who received placebo (n = 157), patients treated with tramadol/acetaminophen (n = 156) showed greater improvement on SF‐36 physical functioning, role physical, bodily pain, and physical summary scales, as well as FIQ scales for ability to do job, pain, and stiffness (P < 0.01).

Conclusion

Moderate‐to‐severe fibromyalgia pain significantly impairs HRQOL, and effective pain relief in these patients significantly increases HRQOL.

     

Anxiety and depressive symptoms and illness perceptions in psoriatic arthritis and associations with physical health‐related quality of life

Objective

Symptoms of psychological distress, including anxiety and depressive symptoms, and illness perceptions are important in determining outcome in patients with rheumatic disease. We aimed to compare psychological distress in psoriatic arthritis (PsA) and rheumatoid arthritis (RA) and to test whether the association between psychological variables and health‐related quality of life (HRQOL) was similar in the 2 forms of arthritis.

Methods

In 83 PsA patients and 199 RA patients, we used the Patient Health Questionnaire 9 (PHQ‐9), the Symptom Checklist‐90‐Revised, and the Brief Illness Perception Questionnaire to assess psychological variables and the World Health Organization Quality of Life Instrument, Short Form to assess HRQOL. We used hierarchical regression analysis to determine the associations between psychological variables and HRQOL after adjusting for demographic variables and disease parameters.

Results

The prevalence of moderate to severe levels of depressive symptoms (PHQ‐9 score ≥10) was 21.7% in PsA patients, 25.1% in RA patients, and 36.7% in those PsA patients with polyarthritis. After adjustment for severity of disease and pain, anxiety (β = ?0.28) and concern about bodily symptoms attributed to the illness (β = ?0.33) were independent correlates of physical HRQOL in PsA. In RA, depressive symptoms (β = ?0.29) and concern about the consequences of the arthritis (β = ?0.27) were independent correlates of physical HRQOL.

Conclusion

These findings suggest strongly that psychological factors are important correlates of HRQOL in PsA as well as in RA. Attention to patients' anxiety and their concern about numerous bodily symptoms attributed to the illness may enable rheumatologists to identify and manage treatable aspects of HRQOL in PsA.

     

Synovial fluid proteins differentiate between the subtypes of juvenile idiopathic arthritis

Objective

Juvenile idiopathic arthritis (JIA) is a heterogeneous group of inflammatory diseases, and no clinically useful prognostic markers to predict disease outcome in children with JIA are currently available. Synovial fluid likely reflects the proteins present in the inflamed synovium. The purpose of this study was to delineate the synovial fluid proteome and determine whether protein expression differs in the different subtypes of JIA.

Methods

Synovial fluid samples obtained from children with oligoarticular JIA, polyarticular JIA, or systemic JIA were compared. Two‐dimensional gel electrophoresis for protein separation and matrix‐assisted laser desorption ionization−time‐of‐flight mass spectrometry and quadripole time‐of‐flight mass spectrometry for protein identification were used for this study. Synovial fluid cells were analyzed by polymerase chain reaction (PCR) for the presence of haptoglobin messenger RNA (mRNA).

Results

The synovial fluid proteome of the samples was delineated. The majority of proteins showed overexpression in JIA synovial fluid as compared with noninflammatory control samples. There were 24 statistically significantly differentially expressed spots (>2‐fold change; P < 0.05) between the subtypes of JIA. PCR analysis revealed haptoglobin mRNA, suggesting that haptoglobin is locally produced in an inflamed joint in JIA.

Conclusion

Despite the similar histologic appearance of inflamed joints in patients with different subtypes of JIA, there are differences in protein expression according to the subtype of JIA. Haptoglobin is differentially expressed between the subtypes of JIA and is locally produced in an inflamed joint in JIA. Haptoglobin and other differentially expressed proteins may be potential biomarkers in JIA.

     

Ongoing disease activity and changing categories in a long‐term nordic cohort study of juvenile idiopathic arthritis

Objective

To describe the disease characteristics, long‐term course, and outcome of patients with juvenile idiopathic arthritis (JIA) in a population‐based setting.

Methods

Consecutive cases of JIA from defined geographic areas of Denmark, Finland, Sweden, and Norway in whom disease onset occurred in 1997–2000 were included in a prospective, multicenter cohort study. The study was designed to be as close to a population‐based study as possible, with centers participating only if they were able to include in their catchment area all children in whom JIA was diagnosed.

Results

Of 500 children included, 440 (88.0%) had repeated visits, with the last visit occurring at least 7 years after disease onset (median 98 months, range 84–147 months). Changes in the International League of Associations for Rheumatology category were observed in 10.8% of the children, and, in addition, extended oligoarthritis developed in 34.7% of the group with oligoarticular JIA. During the observation period, 58.0% of the children were treated with disease‐modifying antirheumatic drugs, including biologic medications. Ongoing disease activity was mostly mild, but some JIA‐related damage developed in 22.9% of the children. At the last followup visit, remission off medication was observed in 42.4% of the children, 8.9% were in remission on medication, and 48.7% were not in remission. The highest rates of remission were observed in patients with persistent oligoarticular JIA and in those with systemic JIA.

Conclusion

In this long‐term prospective study of JIA in a population‐based Nordic setting, ongoing disease was evident in a majority of the children. The present results underline the need to identify early predictors of outcome, to further improve therapy, and to continue long‐term followup of patients with JIA.