COMMENTARY

The Latest in Lupus, Arthritis, and Ankylosing Spondylitis

Ioannis Parodis, MD

Disclosures

August 10, 2016

In This Article

Author's note:
The 2016 European League Against Rheumatism (EULAR) annual meeting was held in London, a city whose elegance and extensive transport network lived up to expectations. With such an ideal venue, and immaculate behind-the-scenes organization, the meeting was a resounding success. In this article, the author provides those unable to attend the conference with some of its key take-home messages. However, the selection of works presented here is unavoidably biased by the author's own interests and appraisements.

New Discoveries in Rheumatoid Arthritis

The use of ultrasound as a tool in the clinical management of patients with rheumatoid arthritis (RA) is gaining in attention. Haavardsholm and colleagues[1] presented results from the randomized, controlled ARCTIC trial (NCT01205854), which examined whether treatment strategies based on ultrasound assessment improve outcomes in RA, compared with those based on clinical and laboratory assessment alone.

Patients with newly diagnosed RA were randomly assigned to either an ultrasound or conventional tight control strategy targeting remission. All patients were treated according to similar principles. The study did not observe significant differences between the arms in terms of achievement of clinical remission, absence of swollen joints, and nonprogression of radiographic joint damage.

It has been suggested that prompt initiation of treatment targeting remission in patients with early arthritis provides an opportunity to achieve quicker drug-free remission. Akdemir and colleagues[2] studied the clinical outcomes of induction therapy followed by 5 years of remission-steered therapy, including rapid tapering strategies.

Remission (defined as a Disease Activity Score < 1.6) and drug-free remission were experienced by 48% and 22%, respectively, of patients with early RA and those with undifferentiated arthritis. Age, symptom duration, baseline tender joint count, and attainment of early remission within 4 months were all identified as predictors of remission, with symptom duration and attainment of early remission predictors of drug-free remission. As expected, drug-free remission was achieved by more patients with undifferentiated arthritis than those with RA, and also by more autoantibody-negative than autoantibody-positive patients.

From the Dose REduction Strategies of Subcutaneous tumor necrosis factor (TNF) inhibitors (DRESS) study, Bouman and coworkers[3] investigated the potential causes of earlier observations that minimal radiographic progression was more frequent in patients who attempted tapering of TNF inhibitors than in those who did not. Of note, the main cause was attributed to higher mean disease activity over time rather than flaring due to dose reduction attempts.

In another exploratory study, Gerlag and colleagues[4] demonstrated that a single 1000-mg infusion of the anti-CD20 monoclonal antibody rituximab significantly delayed the onset of clinically manifest arthritis in patients with arthralgia who were positive for both anti-citrullinated peptide antibodies and rheumatoid factor, had C-reactive protein levels ≥ 3 mg/L, and/or had subclinical synovitis diagnosed via ultrasound or MRI examination of the hands. This study may represent a paradigm shift from treating manifest RA to preventing its onset in individuals at risk of developing RA.

Treatments for Ankylosing Spondylitis

As new therapies for axial spondyloarthritis and psoriatic arthritis have arrived, so too has research interest in these diseases. The interleukin (IL)-17 and IL-22/23 pathways received particular attention during the conference. MEASURE 1 (NCT01358175) is a phase 3 trial in which 371 patients with active ankylosing spondylitis (AS) were randomly assigned to receive either the IL-17A inhibitor secukinumab or placebo.

Patients receiving secukinumab were given a loading dose of 10 mg/kg intravenously at baseline, week 2, and week 4, and either 75 mg or 150 mg subcutaneously every fourth week thereafter from week 8. Patients who received placebo were then rerandomized to receive either secukinumab 75 mg or 150 mg every fourth week. Patients who had a response according to the Assessment in Ankylosing Spondylitis Response Criteria (ASAS20) switched at week 24, and nonresponders switched at week 16. Spinal radiographic changes through 2 years of treatment were assessed by two independent readers who were blinded to treatment arm and radiography sequence.

Braun and coworkers presented results from this assessment.[5] The mean change in the modified Stoke AS Spine Score (mSASSS) was low, with no major difference between the two secukinumab doses. The changes observed were higher in patients who were male, had syndesmophytes at baseline, and/or had elevated C-reactive protein at baseline. There were no major differences in terms of change in mSASSS through week 104 between patients who received secukinumab from the beginning of the study and patients who first received placebo and then switched to secukinumab.

The oral Janus kinase inhibitor tofacitinib, known already in the field of RA, was tested in adult patients with active AS in a 16-week, multicentre, phase 2 dose-ranging trial (NCT01786668). Patients who fulfilled the modified New York criteria for AS (n = 208) were randomly assigned to receive either placebo or tofacitinib at 2, 5, or 10 mg daily for 12 weeks. The primary efficacy endpoint was ASAS20 response rate at week 12; safety endpoints included adverse events and laboratory outcomes. According to the first results from the trial, presented by van der Heijde and colleagues,[6] tofacitinib 5 and 10 mg showed greater clinical and imaging efficacy compared with placebo, and no new safety concerns were identified.

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