Axial Spondyloarthritis: Updated British Guide on Biologics

Janis C. Kelly

September 12, 2016

An updated guideline by two British medical societies is expected to expand access to biologics for patients with axial spondyloarthritis (axSpA; including ankylosing spondylitis [AS]) and increase prescribing flexibility for clinicians in the National Health Service.

The guidance, developed on behalf of the British Society for Rheumatology (BSR) and British Health Professionals in Rheumatology (BHPR) Standards, Guidelines, and Audit Working Group, was published online August 24 in Rheumatology. The group based the guideline on evidence from a systematic literature search of Medline, Embase, and the Cochrane library up to June 30, 2014.

"The main difference [from the 2005 BSR guideline] is that the guidelines apply not just to patients with [AS] meeting the modified New York criteria, but also to those with nonradiographic disease, provided they have objective evidence of inflammation such as bone marrow edema on [magnetic resonance imaging (MRI)] or a raised [C-reactive protein]," lead author Louise Hamilton, MBBS, told Medscape Medical News.

"We also recommend switching [from one tumor necrosis factor (TNF) inhibitor to another] be permitted at any point in the treatment course, whether for reasons of inefficacy or intolerance, and we have reduced the time between [Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)] measurements to 4 weeks (on the grounds that this is sufficient time to ensure you're capturing active disease, not a one-off flare)," she continued. Dr Hamilton is a consultant in rheumatology at Norfolk and Norwich University Hospital, United Kingdom.

The 2016 guideline includes key recommendations on the effectiveness of biologics in axSpA, treatment initiation, drug choice, response assessment, therapy withdrawal, and drug switching. The panel classified axSpA into two subgroups: radiographic axSpA (AS) and nonradiographic axSpA (nr-axSpA). The guideline did not address peripheral spondyloarthritis or juvenile SpA.

The reviewers conclude that anti-TNF therapy is effective at reducing axSpA disease activity and spinal pain, and that short-term MRI data support anti-TNF efficacy in relieving inflammatory sacroiliac joint (SIJ) and spinal lesions, but that evidence of effect on radiographic disease progression is "currently limited." They also found insufficient evidence to support use of any biologic agents other than TNF inhibitors in axSpA.

When to Begin Anti-TNF Treatment?

The question of when to begin anti-TNF treatment in axSpA highlighted some differences between BSR criteria and those of the UK National Institute for Health Care Excellence (NICE), which largely determines treatment availability within the National Health Service. At the time of the data review, NICE required that patients have active spinal disease, defined as (BASDAI and spinal pain visual analogue scale score ≥4 despite standard therapy on two occasions at least 12 weeks apart. The BSR panel reduced this to two occasions at least 4 weeks apart).

Dr Hamilton explained that NICE revised their guidance while the BSR guideline was awaiting publication, and now recommend just one BASDAI. "This is left a bit open, but that's how it's being interpreted," Dr Hamilton said. "In the UK, what NICE says goes, so fortunately there is no conflict here (and they also approved switching, which was a relief). Although the BSR guidelines are only coming out now, they were written before the NICE revision came out, and we didn't know whether clinicians would be able to implement our recommendations; they certainly couldn't have if NICE had said no to switching."

The BSR guideline also advises that patients with active disease who do not meet modified New York criteria for AS should have a positive MRI and/or elevated C-reactive protein levels to be considered for biologic treatment. The authors write, "Prescribers should be confident that worsening symptoms, radiological changes and raised inflammatory markers are due to axSpA and not to other pathology such as malignancy or infection. Discussion with an axSpA specialist should be considered before starting treatment in a patient with nr-axSpA and no SIJ bone marrow oedema on MRI."

Atul Deodhar, MD, MRCP, medical director of Rheumatology Clinics at Oregon Health & Science University, Portland, told Medscape Medical News that the revised BSR guidelines remain much more restrictive than those he helped prepare in 2015 for the American College of Rheumatology/Spondylitis Association of America/Spondyloarthritis Research and Treatment Network for treatment of AS and nr-axSpA. "We did not want to tie up the hands of practicing rheumatologists with fixed assessments," Dr Deodhar said. Dr Deodhar was not involved in the BSR guideline panel.

With regard to choice of TNF inhibitor for AS, the BSR authors conclude that reviews have found no significant efficacy differences among infliximab, golimumab, etanercept, and adalimumab. They note that although certolizumab data were not included in the comparative reviews, clinical trials have established its efficacy. The reviewers found insufficient data to comment on the relative efficacy of different TNF inhibitors in nr-axSpA.

In contrast, the ACR guidelines recommend treatment with infliximab or adalimumab over treatment with etanercept for patients with AS and recurrent iritis, as well as treatment with infliximab, rather than etanercept, for patients with AS with concomitant IBD.

Monitor Clinical Response

The BSR guideline recommends assessing treatment response after 3 to 6 months and reassessing responders (defined as having a reduction from baseline of at least 2 units in BASDAI and spinal pain visual analogue scale) every 6 months thereafter. Clinicians should consider withdrawing treatment if there is no clinical response by 6 months or if response is not maintained at two consecutive assessments.

The reviewers recommend switching to a different TNF inhibitor "in the event of anti-TNF failure due to inefficacy or adverse events."

Both Dr Hamilton and Dr Deodhar told Medscape Medical News that the key unanswered question in AS is whether biologics prevent radiographic progression. Dr Hamilton added, "And by treating early disease (ie, nonradiographic), can you achieve drug-free remission, or are you overtreating people who would never have developed AS?"

Dr Deodhar said, "The biggest unanswered questions are whether biologic therapies prevent new bone formation (are they [disease-modifying antirheumatic drugs]), whether biologic therapy prevents conversion of nr-axSpA to AS, how does secukinumab [an interleukin (IL)-17A inhibitor] compare with TNF inhibitors, and which biologic therapy would you choose first: TNF inhibitors, or secukinumab?"

Dr Hamilton has received unit funding from AbbVie, MSD, Pfizer and UCB; was sponsored to attend a meeting by MSD; and has received a research grant from Pfizer. Other coauthors reported funding and/or honoraria from Pfizer, AbbVie, MSD, UCB, Novartis, Janssen, Roche, Boehringer Ingelheim, Wyeth, and Celgene. Dr Deodhar participated in clinical trials of secukinumab funded by Novartis, has received research grants and served on advisory boards of Eli Lilly, Janssen, Novartis, Pfizer, and UCB.

Rheumatology. Published online August 24, 2016. Full text

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