American College of Rheumatology/Association of Rheumatology Health Professionals (ACR/ARHP) 2012 Annual Meeting

November 9-14, 2012; Washington, DC

Depression and Mortality Associated With Rheumatoid Arthritis

Although rates of depression are increased among people with rheumatoid arthritis (RA) and studies of elderly people and cardiovascular disease show depression as a risk factor for mortality, little attention has been paid to the potential risk of mortality in RA patients with depression. A study presented by Patricia Katz, PhD, associate professor of medicine and health policy, Division of Rheumatology, University of California, San Francisco, and colleagues at the ACR/ARHP 2012 meeting shed light on this issue. The study found an increase in all-cause mortality associated with depression in RA patients, and Katz noted that identifying and managing depression in people with RA, particularly in men, is important.

Katz and colleagues conducted a longitudinal cohort study of people with RA recruited from community rheumatology practices in Northern California. Using annual telephone surveys, the investigators collected data from 530 people with RA to assess symptoms of depression as well as the potential impact of the disease. Mean age of the participants was 60 years, with a mean disease duration of 19 years. Most were women (84%), and 46% reported at least one cardiovascular disease risk factor. All people included in the survey were required to score ≥5 on the Geriatric Depression Scale (GDS), to have undergone a telephone interview in either 2002 or 2003 (with at least one follow-up interview), and to have been followed until 2009.

Using Cox regression models, the investigators estimated the association between depression and all-cause mortality based on two analyses. One analysis examined all-cause mortality risk associated with depression as defined as a GDS score >5 in the last interview before death or censorship. The second analysis examined all-cause mortality risk associated with a 2-point increase in GDS score from the penultimate to the last interview before death or censorship. Both analyses controlled for sex, age, disease duration, and cardiovascular disease risk factors.

At a mean follow-up of 4.9 years until death or censorship, the study found that 63 of the 530 (12%) participants died. Under both analyses, the study found that depression was associated with an increased risk of death (hazard ratio [HR], 3.5; 95% confidence interval [CI], 2.1-5.8). Mortality risk was also associated with depression when looking at a worsening of GDS score by >2 points (HR, 2.5; 95% CI, 1.5-4.2). This increased mortality risk associated with depression remained when controlling for age, disease duration, and cardiovascular risk factors.

In separate analyses that examined the effects of both sex and depression on increased mortality risk, the study found that men without depression had five times the risk of death compared with women without depression (HR, 5.1; 95% CI, 2.2-11.8 vs HR, 1, respectively, based on worsening of GDS score by >2 points; and HR, 5.9; 95% CI, 2.7-13.1 vs HR, 1, respectively, based on baseline GDS score >5).

After controlling for covariates, a greater mortality risk was still observed in men without depression compared with women without depression. Based on these findings, healthcare providers need to be aware of the problem of depression in RA patients, said Katz. She also emphasized the need for strategies to motivate men in particular to seek treatment for their depression, including regular monitoring of depression in a way that enables them to provide information on manifestations of depressive symptoms, which may be achieved by healthcare providers using motivational interviewing techniques to help handle resistance to treatment and downplaying of symptoms.
—Mary Beth Nierengarten

Use of Disease-Modifying Antirheumatic Drugs Low Among Unsubsidized Medicare Beneficiaries With Rheumatoid Arthritis

Results of a study presented at the ACR/ARHP 2012 meeting suggest that the choice of biologic disease-modifying antirheumatic drugs (DMARDs) for patients with rheumatoid arthritis (RA) who receive care through Medicare may be influenced by subsidy status, rather than clinical factors that balance risks, benefits, and patient preference.

Conducted by investigators from the University of California, San Francisco, the study examined the potential impact of cost-sharing for Medicare beneficiaries. The authors compared drug use and out-of-pocket (OOP) costs for biologic and nonbiologic DMARDs for patients with RA who reach the coverage gap (or donut hole) in Part D with patients with RA who are eligible for a low-income subsidy (LIS) with reduced cost-sharing.

Under Part D, patients pay 100% of drug costs when the cost of their drugs reaches $2700 through $6514. This is considered the coverage gap period, or donut hole. Prior to and after these amounts, Medicare picks up the majority of the expense.

The need to see how the design of Part D affects utilization of DMARDs for RA in Medicare beneficiaries is important given the high cost of these drugs, particularly injectable biologics. Jinoos Yazdany, MD, MPH, a co-investigator of the study who presented the results, emphasized that there are no generic treatments with the biologic agents, and that all RA patients on DMARDs will reach the donut hole when taking these drugs.

Using data from a 5% random sample of Medicare fee-for-service claims for 2009 linked to Part D prescription drug files, the study included 5808 patients who were ≥65 years of age, had two or more face-to-face encounters for RA, were continuously enrolled in a Part D drug plan, and had one or more DMARD prescription. The mean age of the patients was 76 years, 82% were women, 85% were white, 97% had received any nonbiologic DMARD, and 11% had received any biologic DMARD.

Of the 5808 patients, 1414 (24%) received the LIS whereby their OOP costs were reduced and not affected when reaching the donut hole, unlike the 70% of other Medicare beneficiaries who were responsible for covering the cost of the drugs during the coverage gap.

The study compared the mean annual RA drug OOP costs per patient in those using biologic DMARDs (with or without nonbiologic DMARDs) with those using only nonbiologic DMARDs. It also compared patients who had no, partial, or full coverage during the gap phase with patients who were eligible for an LIS.

Of the patients, 679 (12%) used biologic DMARDs and 5129 (88%) used nonbiologic DMARDs. In addition, 44% of patients who used biologic DMARDs received a LIS compared with 22% of nonbiologic DMARD users.

The OOP annual costs for biologic DMARDs were low for the patients eligible for an LIS ($26) compared with the unsubsidized patients OOP annual costs ($3009); this was similarly true for nonbiologic DMARD use between the two groups ($11 vs $85, respectively). The largest OOP cost was incurred for the biologic DMARDs during the coverage gap, which totaled about $2347 for unsubsidized beneficiaries.

The study also looked at biologic DMARD use as covered by Medicare Part D and Part B and found that most unsubsidized patients received their biologics through Part B.

Significantly more beneficiaries enrolled in an LIS program received biologic DMARDs compared with those who used nonbiologic DMARDs. Although more work is needed to determine whether the low rate of use of biologic DMARDs among unsubsidized beneficiaries is a consequence of substantial cost-sharing, Yazdany advocated for a more coherent coverage of the biologics. She also emphasized the importance of balancing short-term costs of newer drugs with long-term costs to society and the need for medical necessity to drive treatment decisions.—Mary Beth Nierengarten

Allopurinol May Not Sufficiently Achieve Target Serum Uric Acid Levels in Patients With Gout

Inflammation and severe pain are common symptoms of gout in older adults, but over time deposits of uric acid crystals may cause joint deformity, resulting in severe disability. In nursing home residents, many of whom have renal insufficiency, serum uric acid (SUA) levels and activities of daily living (ADLs) require evaluation and resident care management. During a poster session at the ACR/ARHP meeting, Joy Higa, Takeda Pharmaceuticals, and colleagues reported the findings of a study that compared patients’ characteristics, SUA levels, and ADLs while taking allopurinol. 

Between October 2010 and March 2011, the researchers conducted on-site chart reviews of 14 Hawaii-based nursing homes. The charts included patients’ serum creatinine levels, SUA levels, characteristics from the Minimum Data Set (MDS), and medication records. Patients were considered eligible for the study if they were above the age of 65 years, had been a nursing home resident for more than 30 days, and had recent SUA and ADL assessments. Residents with gout taking allopurinol (identified by the term “cases”; n=202) were compared with a control group of patients without gout who were identified by simple random sampling from the same time frame (two controls per case, n=404). A global ADL score was calculated from the most recent MDS per the Carpenter study (BMC Geriatr. 2006;6:7). 

The team found that of the nursing home residents with gout, 69% had SUA levels ≥6 mg/dL despite allopurinol treatment. Age was found to be a related factor. When compared with the control group, residents with SUA levels ≥6 mg/dL were more likely to be younger than 85 years (39% vs 53%; P<.001) and more likely to be of Hawaiian ancestry (odds ratio [OR]=7.3;P<.001). Cases in this study were more likely to have coronary artery disease (OR=4.0; P<.001), diabetes (OR=3.6; P<.001), previous myocardial infarction (OR=7.3; P<.001), and charted renal failure (OR=4.9; P<.001). Body mass index was also 2.3 points higher for cases of gout versus the control group (P<.001). Gout was independently associated with a 7.26-point higher Carpenter ADL score (P<.001). Cases were also more likely to receive an opiate than the control arm (adjusted OR=8.7; P<.001). 

Higa and colleagues concluded that gout is independently associated with worsened ADL scores and they should be factored into pre-admission evaluation upon entering a nursing home. Furthermore, they noted, allopurinol may not be sufficient to achieve target SUA levels, even when given at maximum renally-adjusted doses.—Kerri Fitzgerald

CAPRA-2 Trial Finds Prednisone May Improve Rheumatoid Arthritis–Associated Fatigue

For patients with rheumatoid arthritis (RA), disease-related pain and inflammation can cause fatigue and negatively impact overall quality of life. Recent studies have shown that glucocorticoid treatment and chronotherapy with delayed-release prednisone may improve patient-reported fatigue. During a poster session at the ACR/ARHP meeting, Rieke Alten, Schlosspark-Klinik, University Medicine, Germany, and colleagues analyzed the results of the CAPRA-2 trial (Circadian Administration of Prednisone in Rheumatoid Arthritis-2) and found that delayed-release prednisone may  significantly reduce fatigue in RA patients.

During a 12-week, double-blind, placebo-controlled study, 350 patients with RA were randomized to receive either 5 mg delayed-release prednisone (n=231) or placebo (n=119) taken once daily at bedtime in addition to standard treatment with a disease-modifying antirheumatic drug. At the 12-week follow-up, the primary end point of the study was the proportion of patients achieving a 20% improvement in tender or swollen joints, as defined by the American College of Rheumatology criteria (ACR20). One of the secondary objectives was to observe improvement in fatigue symptoms, measured by change from baseline status on the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) questionnaire. The FACIT-F is a 13-item questionnaire that assesses the effect of fatigue on daily activity and function on a 5-point scale with a total score range of 0 to 52. 

The results of their analysis showed mean baseline scores on the FACIT-F were comparable between the prednisone group and the placebo group (28.81 vs 28.73). By week 12, the difference in FACIT-F score between these two groups reached clinical significance. At week 12, the least square mean (LSM) change from baseline was significantly greater for 5 mg delayed-release prednisone than for placebo (LSM difference=2.24; 95% confidence interval, 0.76, 3.72; P=.0032). The findings were consistent with improvement in ACR20 score.

The study concluded that patients treated with 5 mg delayed-release prednisone demonstrated significant improvements in their FACIT-F scores when compared with patients receiving placebo, which indicates a reduction in fatigue and, therefore, a major improvement to quality of life for RA patients. The authors concluded, “chronotherapy with a [delayed-release] prednisone formulation improves ACR scores and provides a potential new treatment option for patients with RA that can also improve symptoms of fatigue.”—Kerri Fitzgerald

Researchers Analyze Relationships Between Morning Stiffness Severity and Duration in Patients With Rheumatoid Arthritis

Morning stiffness (MS), which is commonly reported by patients with rheumatoid arthritis (RA), is predictive of functional disability and escalated RA care in older adults; however, clinicians are still unsure of the best way to evaluate MS in RA patients. A recent study, presented in a poster session at the ACR/ARHP meeting, reported that morning pain, MS severity, and MS duration are the key patient-reported outcomes in RA treatment response and disease progression. In this study, Frank Buttgereit, MD, Charite University Medicine, Berlin, and colleagues examined data taken from CAPRA-2 (Circadian Administration of Prednisone in Rheumatoid Arthritis-2), a study in which RA patients were randomized to receive either 5 mg delayed-release prednisone (n=231) or placebo (n=119) in addition to standard treatment with an antirheumatic disease-modifying drug. The primary end point at the 12 week-follow-up was the proportion of patients achieving a response according to the American College of Rheumatology criteria (ACR20). A secondary objective was a reduction in patients’ self-reported MS. The team used these data to evaluate MS duration, MS severity, and pain intensity (PI) in patients upon waking, with other RA measures representing disease progression and response, to determine if one is more clearly related to the disease activity. The extent of these relationships were assessed using patient response criteria from the ACR20, the Disease Activity Score 28 Calculator (DAS28), and the Health Assessment Questionnaire for Rheumatoid Arthritis (HAQ-DI).

Changes from baseline in MS duration, MS severity, and PI were assessed using Pearson Correlations. In addition, a Wilcoxon rank sum analysis was completed between responders and nonresponders based on MS duration, ACR20, DAS28, and HAQ-DI. The results of the study indicated significant correlations among MS duration, MS severity, and PI with the DAS28 and HAQ-DI in all group analyses (P<.0001). There were stronger absolute correlations seen with MS severity and PI when compared with MS duration. A moderately strong correlation was seen between DAS28 and MS severity and PI in both the treatment and placebo groups. Overall, MS severity and PI were strongly correlated. 

The authors noted that the findings in this study were consistent with previous studies showing that joint impairment is moderately correlated with disability, as measured by self-report questionnaires. The researchers found that responders had a greater relative reduction in MS duration than non-responders, especially in the RA patients treated with delayed-release prednisone. 

The authors concluded, “Patients who met ACR20, DAS28, and HAQ-DI response criteria had a significantly greater reduction in MS than nonresponders.”—Kerri Fitzgerald

Study Examines Effect of TNF Inhibitors on MRSA Carriage in Patients With Rheumatologic Disease

Methicillin-resistant Staphylococcus aureus (MRSA) presents great risk for patients and healthcare providers, representing a significant source of financial burden and morbidity and mortality. While numerous studies of MRSA have assessed the relationship between colonization and drugs with immunosuppressive properties, they tend to be limited to transplant patients, cancer patients, and those with human immunodeficiency virus. In a poster session at the ACR/ARHP meeting, Daniel E. Kreutz, MD, and colleagues, Scott & White Healthcare/Texas A&M University, presented the findings of their study, which sought to identify the influence of tumor necrosis factor (TNF) inhibitor drugs on MRSA carrier states in patients with psoriasis (PS), psoriatic arthritis (PsA), rheumatoid arthritis (RA), or ankylosing spondylitis (AS). 

Medical records of patients admitted to two large referral hospitals between January 1, 2007, and March 31, 2010, were reviewed for this study. Eligible patients were adults aged 18 years or older with PS, PsA, RA, or AS admitted during this time period (N=1001). Using a retrospective chart review, 436 patients were screened for nasal MRSA, which is the most common colonization site.

Of this group with nasal MRSA, 10 patients (2.3%) had PsA, 15 (3.4%) had AS, 72 (16.5%) had PS, and 341 (78.2%) had RA. Approximately 12% of patients (n=53) were noted to have MRSA colonization, compared with the overall rate of 6.7% in adults. Additionally, 12.4% (n=54) of patients had a TNF inhibitor in their medication regimen, 11.1% of whom were MRSA-positive. 

The study found patients with MRSA tended to have a longer length of hospital stay (P=.0529) and were more likely to have come from a nursing home (27.5%). The presence of MRSA was strongly associated with nursing home residence, the authors noted (P=.0003).

The researchers concluded that patients with PS and rheumatologic diseases had a higher rate of MRSA colonization than the general patient population who participated in the study. Patients treated with TNF inhibitors were no more likely than those being treated with traditional immune modulating agents to have a MRSA-positive screen, they noted. Additionally, patients transferred from a nursing facility to the hospital were more likely to have a MRSA-positive screen.—Kerri Fitzgerald