VBCR - October 2016, Vol 5, No 5 - In the Literature

In This Article

Impact of Biologic DMARDs Treatment on Risk for Sepsis or Mortality in Patients with Rheumatoid Arthritis

It is well known that biologic disease-modifying antirheumatic drugs (bDMARDs) increase the risk for serious infection, and that sepsis is a potentially fatal sequela of serious infection. An observational cohort study of patients with rheumatoid arthritis (RA) enrolled in the German biologics register RABBIT (RA: Observation of Biologic Therapy) demonstrated that bDMARDs appear to have a protective effect against the risk for sepsis after serious infection, as well as against the risk for a fatal outcome (Richter A, et al. Ann Rheum Dis. 2016;75:1667-1673). This is an early study, and further investigation is needed to validate these results, according to the researchers.

This study suggests, but does not prove, that successful immunosuppression may prevent an unregulated host response to serious infection and escalation to sepsis.

“This is the first study that investigated simultaneously the risks of sepsis and mortality as possible outcomes of SIs [serious infections] in patients with RA,” the investigators explained.

Sepsis occurred in the 30 days after serious infection in 135 of 947 patients; 85 of the patients died. A serious infection escalated to sepsis or death in 1 of 5 patients. A total of 53 patients who did not have documented sepsis died within 90 days of serious infection. In an adjusted analysis, older age and chronic renal disease increased the risk for developing sepsis. Heart failure, renal disease, and age were associated with increased risk for both serious infection and sepsis.

Compared with conventional DMARDs, the risks for sepsis and fatal outcomes of serious infection were significantly lower when patients were exposed to bDMARDs at the time of serious infection.

Risk factors associated with fatal serious infections were older age, use of higher doses of glucocorticoids, and heart failure. Factors associated with lower mortality risk with a serious in­fection included treatment with bDMARDs and better physical function.

The study was based on outcomes in 947 patients with RA. These outcomes were recovery without complication, sepsis within 30 days of serious in­fection, and death within 90 days of serious infection without known sepsis.

Another important finding of the study was that the protective effect of bDMARDs diminished when treatment with these agents was discontinued. In addition, adverse outcomes of serious infection (eg, death or sepsis) were more likely to occur in patients who were biologic-naïve than in those exposed to bDMARDs at the time of serious infection.

These findings, related to discontinuation of bDMARDs, appear to raise more questions, and further study is needed to determine the associated risks.

“We cannot conclude from our study that bDMARDs should be continued in case of an SI [serious infection] since this is the first study showing these results. They have to be confirmed by other studies before any clinical consequences can be drawn,” the researchers concluded.

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Skin Temperature Screenings for Progressive Rheumatoid Arthritis

Measuring the skin temperature over an inflamed (ie, “hot”) joint can identify patients with RA who are most likely to sustain radiographic damage within 1 year, according to the results of a recent observational study (Greenwald M, et al. Arthritis Care Res [Hoboken]. 2016;68:1201-1205). This simple, widely available, and inexpensive tool may replace more expensive and time-consuming strategies used to identify patients who need more aggressive therapy (eg, biologics).

“Our findings suggest that dermal temperature can quickly and accurately identify individual, specific RA patients at high risk for further destructive change. Patients with hot joints had a nearly 4-fold higher risk of new radiographic damage than those with cool joints, and more than 70% of patients with hot joints had clear radiographic evidence of new destructive radiographic joint damage 1 year later. Joint temperature had high sensitivity and specificity for predicting new damage in the next year,” the investigators reported.

Currently used prognostic factors (eg, age, early disease onset, and seropositive status) are typically augmented with laboratory tests and scales to measure inflammation as well as imaging of joints and functional assessment tools. These complex workups can be time-consuming and costly.

“There is a need for a simple, cost-effective tool for determining which patients will develop progressive, destructive RA,” the researchers explained. They also stated that the main objective of their study was to identify a single assessment tool “that could be used easily from Uganda to Uruguay, and not involve subjective measurement, literacy, high cost, or a lot of time.”

The study included 208 patients with seropositive RA who were naïve to biologic therapy and maintained on a stable dosage of methotrexate: 104 fell into the hot-joint category, and 104 into the cool-joint category. The hot-joint cohort had a joint skin temperature greater than their body temperature. Hand and wrist radiographs were obtained at baseline and 1 year after enrollment, and scored using a single reader.

At baseline, the hot-joint cohort had active inflammatory disease, were younger, and had less time since diagnosis compared with the cool-joint cohort. Baseline C-reactive protein levels and the percentage of women were similar in both cohorts.

Patients with hot joints had a mean joint temperature 1.06°F above central body temperature, and an approximately 4-fold higher risk for new radiographic damage compared with those with cool joints (Sharp/van der Heijde score 8.7 vs 2.5, respectively; P <.001). At 1 year, changes in Sharp/van der Heijde scores were significantly greater among the hot-joint cohort compared with the cool-joint group (P <.001).

Among those with hot joints, 77 (74%) patients had clear radiographic evidence of new joint damage, and the remaining 27 (26%) had no radiographic evidence of progressive, destructive disease. Among the patients with cool joints, 97 (93%) had no radiographic evidence of new joint damage, whereas the remaining 7 (7%) patients had bone or cartilage damage.

The sensitivity and specificity of using joint temperature to predict joint damage occurrence were 92% and 78%, respectively.

These results suggest that serum markers, such as erythrocyte sedimentation rate and C-reactive protein, may not be necessary to identify patients at high risk for radiographic progression. These markers are poorly correlated with radiographic progression in patients with RA, and require added time and costs. In addition, scales such as the American College of Rheumatology 20% improvement criteria, Disease Activity Score, Health Assessment Questionnaire, and Routine Assessment of Patient Index Data require time-consuming questionnaires, clinical assessments, and scoring.

Joint temperature is a simple clinical assessment that patients can easily understand and relate to, and may positively impact acceptance of therapy and adherence, the investigators asserted. Unlike with other assessment tools, it takes <1 minute to assess joint temperature as part of ascertaining vital signs, and at no added cost.

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EULAR Revises Its Recommendations for the Management of Fibromyalgia

Although fibromyalgia is common—with 2% prevalence in the general population—diagnosis and management of the condition remain a challenge for patients and healthcare providers. Through the use of qualitative systematic reviews, a working group for the European League Against Rheumatism (EULAR) has developed new recommendations that incorporate a decade of evidence in relation to pharmacologic and non­pharmacologic fibromyalgia management (Macfarlane GJ, et al. Ann Rheum Dis. 2016 Jul 4. Epub ahead of print). It has also identified and proposed priority areas for future research.

“The original European League Against Rheumatism (EULAR) recommendations for the management of fibromyalgia assessed evidence up to and including 2005,” the investigators explained. “Given the paucity of information and poor quality of the studies available, it was recommended that the guidelines be revised after a period of 4 years. However, no subsequent revision took place and thus a decade later we revisit the recommendations with the aim of making them more evidence based.”

An 18-member, multidisciplinary working group that included clinicians, nonclinical scientists, patients, patient representatives, and nurses evaluated data with a focus on systematic reviews and meta-analyses concerned with pharmacologic and nonpharmacologic management of fibromyalgia. A total of 2979 titles were identified, from which 275 full papers were selected for review, and 107 reviews were evaluated as eligible for consideration.

Pharmacologic (eg, amitriptyline, cyclobenzaprine, monoamine oxidase inhibitors) and nonpharmacologic (eg, exercise, massage, acupuncture) therapies were evaluated and categorized according to the 4-point Grading of Recommendations Assessment, Development and Evaluation system. Per this scale, recommendations are considered strong for, weak for, weak against, strong against. Recommendations may also be deemed as “use only for research.”

“The strength of recommendation is based on the balance between desirable and undesirable effects (considering values and preferences), confidence in the magnitude of effects and resource use,” according to the researcher. “A strong recommendation implies that, if presented with the evidence, all or almost all informed persons would make the recommendation for or against the therapy, while a weak recommendation would imply that most people would, although a substantial minority would not.”

Per the meta-analyses, exercise was the only guideline recommendation deemed “strong for.” According to expert opinion, initial management of fibromyalgia should involve patient education and focus on nonpharmacologic therapies. In nonresponsive situations, further therapies—all of which were evaluated as “weak for”—should be individualized to the specific needs of the patient. These may include psychologic therapies (for mood disorders and unhelpful coping strategies), pharmacotherapy (for severe pain or sleep disturbance), and a multimodal rehabilitation program (for severe disability).

“We were unanimous in providing a ‘strong for’ recommendation for the use of exercise, particularly given its effect on pain, physical function and well-being, availability, relatively low cost and lack of safety concerns,” the investigators stated.

“Despite the very large increase in the amount of trial data summarised in meta-analyses, there are no major changes to the approach of managing patients with fibromyalgia, although we provide new evidence in support for some additional nonpharmacological therapies,” they added.

According to the researchers, these recommendations will undergo dissemination by the international working group via national rheumatology societies (eg, scientific meetings, newsletters, and continuing education programs).

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