Response to NSAID Treatment Similar Among Patients with AS and Nonradiographic Axial SpA

VBCR - April 2017, Vol 6, No 1 - In the Literature

Results from a recent study show that patients with ankylosing spondylitis (AS) and nonradiographic axial spondyloarthritis (nr-axSpA) responded similarly to treatment with nonsteroidal anti-inflammatory drugs (NSAIDs) administered in accordance with current treatment recommendations from the Assessment of SpondyloArthritis International Society (ASAS) and the European League Against Rheumatism (EULAR; Baraliakos X, et al. Rheumatology [Oxford]. 2017;56:95-102). The significance of these results, according to the investigators, lies in their corroboration of existing literature demonstrating the many clinical similarities between patients with AS and nr-axSpA with regard to disease burden and response to anti–tumor necrosis factor (TNF) treatment.

In their effort to study the percentage of patients with AS and nr-axSpA who respond to treatment with NSAIDs as proposed by ASAS/EULAR recommendations, the researchers provided 100 patients (50 with AS and 50 with nr-axSpA) with a continuous regimen of NSAID therapy at the maximum recommended or tolerated dose for 4 weeks and then prospectively compared their responses. Patients were only included in the analysis if they had a Bath Ankylosing Spondylitis Disease Activity Index score of 54/10, and if they were naïve to anti-TNF drugs.

Participants underwent clinical visits before beginning treatment, and then after weeks 1 and 4 of treatment. Although all patients had magnetic resonance imaging (MRI) of their sacroiliac joint conducted at baseline, financial constraints allowed only 60 patients to receive a follow-up MRI after week 4.

Aside from C-reactive protein levels and MRI results, patients experienced significant disease activity improvement in all clinical assessments between baseline and week 4. With regard to response rates, 15 (30%) patients with nr-axSpA and 20 (40%) patients with AS achieved an ASAS 40% response at week 4. An ASAS partial remission was achieved in 7 (14%) patients with nr-axSpA and 9 (18%) patients with AS during the same time frame.

“In this prospective study we show that many patients with axSpA still have active disease after the recommended 4 weeks of NSAID therapy, although the majority improved. There was no difference between patients with nr-axSpA and AS,” the investigators concluded.

Allopurinol plus Lesinurad versus Allopurinol Monotherapy in Patients with Gout

Combination treatment consisting of allopurinol and lesinurad led to a greater decrease in serum urate levels in patients with gout compared with allo­purinol as monotherapy, and serves as a novel option for patients in need of therapy for lowering urate levels, according to the results of a recent, randomized, double-blind clinical trial (Saag KG, et al. Arthritis Rheumatol. 2017;69:203-212).

Despite being recommended as a first-line urate-lowering therapy in treatment guidelines for the management of patients with gout, allopurinol administered at the most common dosage of 300 mg daily does not lead to the achievement of a serum urate target of <6.0 mg/dL in >50% of patients in clinical trials. However, treatment with allopurinol plus lesinurad, a new, selective uric acid reabsorption inhibitor indicated for use in patients with gout in combination with a xanthine oxidase inhibitor, has been shown to benefit patients more than allopurinol monotherapy in terms of reducing serum urate levels.

To examine the percentage of patients who achieve a serum urate level of <6.0 mg/dL following 6 months of therapy with combination treatment versus allopurinol alone, the investigators conducted a phase 3, placebo-controlled, multicenter study of 603 patients with gout whose serum urate levels were ≥6.5 mg/dL at the time of screening.

Patients were randomized to receive an addition of lesinurad 200 mg or 400 mg daily, or placebo, to their existing allopurinol treatment. Over the course of the year-long study, patients were evaluated for achieving the target serum urate level at month 6, and assessed for secondary end points (eg, mean rate of therapy-requiring gout flares from months 6-12) at the end of month 12. Comparisons of serum urate levels between the regimen groups were conducted with the use of the Cochran-Mantel-Haenszel test statistic and a Bonferroni correction.

At month 6, 27.9% of patients receiving allopurinol monotherapy, 54.2% receiving allopurinol plus lesin­urad 200 mg, and 59.2% receiving allopurinol plus lesinurad 400 mg achieved the primary end point of reaching a serum urate level of <6.0 mg/dL.

“This represents a significant difference for each of the groups taking lesinurad plus allopurinol as compared with allopurinol alone,” the researchers stated.

With regard to the secondary end point of the rate of gout flares requiring treatment between months 6 and 12, the proportion of patients who experienced gout flares that necessitated therapy were low and similar among all study cohorts.

“Combination therapy with lesinurad and allopurinol may represent a treatment option for patients with gout in whom target levels of serum UA [urate] cannot be achieved with a xanthine oxidase inhibitor alone and additional therapy is warranted,” the investigators concluded.

Treatment Strategies for Patients in the Early Stage of RA Should Account for Comorbidities

According to the results of a recent study, there has been an increase in the age of onset, as well as the burden of comorbidities, in patients when they initially present with rheumatoid arthritis (RA) over the past 25 years (Nikiphorou E, et al. Arthritis Care Res [Hoboken]. 2017;69:21-27). These findings, in addition to the effect comorbidities have on disease outcomes and pharmacotherapy choices, underscore the need for examining coexisting conditions when patients first present with RA, the study researchers asserted.

“This study provides insights into the changing circumstances of the first presentation of RA over 25 years, which may have important clinical and health economic implications for, as an example, the screening and management of comorbid diseases, treatment stratification, and resource allocation,” the researchers said.

Using data from the Early Rheumatoid Arthritis Study and Early Rheumatoid Arthritis Network, both of which are multicenter initiation cohorts of early RA, investigators sought to determine any alterations in the past 25 years in the demographics, clinical characteristics, and presence of comorbidities in patients first presenting with RA who have not begun therapy with disease-modifying antirheumatic drugs. Data from 2701 patients were included in the study. The investigators estimated 25-year trends in demographics and comorbidities using mixed-effects models.

Results of the study demonstrated that over the course of 25 years, the commonness of comorbid conditions at RA presentation increased significantly, especially with regard to cardiovascular and noncardiovascular morbidity. The investigators noted that these results also coincide with demographic changes seen over time in the general population, with an increased occurrence of multimorbidity and obesity in particular.

“Whether these observed changes in comorbidity represent a real increase in conditions or are alternatively due to improved recognition, the fact is that the recognized burden of comorbidity has increased and as such this should impact on modern rheumatology management,” they reported.

Because of the health burden carried by these comorbid conditions and others, the researchers stress the need for placing emphasis on the screening and addressing of comorbidity risk factors, and assert that the findings of their study support these interventions to improve outcomes and treatment responses in patients who are diagnosed with RA.

“We propose that clinicians in busy clinical settings should screen for comorbidity, at the very least for the specific conditions we have identified in this report, based on their frequency, potential impact on RA outcome, and the availability of relative simple screening tools, with care plans in place for rapid referral to other specialists as necessary,” they concluded.

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