Should biologics be used as first-line therapy in the treatment of spondyloarthritides (SpA) or are NSAIDs still the preferred option? A pro-and-con discussion explored this question at this year’s DGIM Congress.
Prof. Dr. Elisabeth Märker-Hermann from Internal Medicine IV of the Helios Dr. Horst Schmidt Kliniken in Wiesbaden (D) took the pro-biologics position. Their statement: a very clear yes for biologics first line in spondyloarthritides – if the diagnosis is certain [1]. And that’s where the problems begin, because axial spondyloarthritides (axSpA) have classification criteria but no diagnostic criteria, and many symptoms and manifestations of nonradiologic SpA have clinically and imaging (especially MRI) relevant differential diagnoses.
Especially in the case of edema on MRI of the ISG, strain-induced symptoms and osteitis condensans would have to be excluded, and enthesitis is an often difficult differential diagnosis to fibromyalgia. The good therapeutic response to NSAIDs can even be used as a diagnostic criterion: “Conversely, if a patient does not respond at all to a sufficient dose of NSAIDs, you have to ask yourself whether he really has SpA. However, this becomes apparent after only a few days of adequately adjusted NSAID therapy.
Conventional DMARDs such as sulfasalazine, leflunomide, or methotrexate are largely ineffective in the treatment of AS patients, the rheumatologist said. The same is true for low-dose corticosteroids, especially in axial SpA, he said. The EULAR recommendations provide for sulfasalazine and local corticosteroids for peripheral manifestation, but systemic steroids or conventional synthetic (cs)DMARDs are not provided for axial manifestation. After initial NSAIDs, direct biologic DMARDs (TNF-α and IL-17 inhibitors) are indicated here.
Time for NSAIDs is getting shorter
Over the years and guideline updates, the time to switch from first line NSAIDs to biologics in axSpA has become shorter and shorter: in 2006, the ASAS/EULAR recommendations still recommended a therapy of at least three months at the maximum dose, with the use of min. three different NSAIDs. In 2017, the period was already reduced to four weeks under min. two NSAIDs reduced before biologics should be used. Finally, in the current 2023 recommendation, it is possible to ask for a change after only 2-4 weeks (Fig. 1) [2].
Important for Prof. Märker-Hermann in individualizing a therapy decision: Are there predictors for a good response? With regard to TNFi, the expert referred to study results according to which a short symptom duration (<5 years) and increased CRP values were significant factors for the success of a therapy. She cited young age, positive HLA-B27, good physical functioning, presence of peripheral arthritis, and male sex as other predictors of a good response to TNFi therapy.
Contra: Partial remission also possible without biologics
Dr. Uta Kiltz, Rheumazentrum Ruhrgebiet Herne, Ruhr-Universität Bochum, also emphasized the distinction between axial and peripheral SpA. She took the contra position [3]: In addition to discussing NSAIDs vs. biologics, she also wanted to make a clear statement in favor of first-line nonpharmacologic treatment options. In addition to lifestyle modifications (stop smoking!), these are – as also recommended by ASAS/EULAR – above all physiotherapeutic measures: “You can prescribe as many biologics as you like, but if exercise therapy is not carried out and adhered to, the majority of patients will not achieve a sufficiently good response over a long period of time.
Both traditional and COX-2-selective NSAIDs have been shown to be effective in axial SpA in trials, he said. Similar to the previous speaker, Dr. Kiltz emphasized the time dependency: the earlier the treatment is started, the more effective the NSAIDs. As much as the therapeutic response may be convincing when biologics are initiated, the rheumatologist also points to a group of NSAID patients who also achieve an ASAS-40 response in some cases. There are also data on partial remission for some of the patients.
The INFAST study included only patients with short axSpA duration (n=156, symptom duration ≤3 years) who received either high-dose NSAIDs (naproxen) or a TNF inhibitor (infliximab) + NSAIDs [4]. In this study, 35% of patients achieved partial remission at week 28 (Fig. 2). “Thus, in one-third of early-stage sufferers, a nearly symptom-free state could be achieved with NSAID-only therapy.”
It must be conceded without question that the data for biologics in SpA are very good, Dr. Kiltz concluded. Nevertheless, she said she sees room for csDMARD or NSAID therapy in a proportion of patients with spondyloarthritides.
Congress: DGIM 2023
Sources:
- Sitzung «Biologika als First Line Therapie, ja oder nein?», Vortrag «… bei Spondyloarthritiden unbedingt! – Pro», 129. Kongress der DGIM, 22.04.2023.
- Ramiro S, Nikiphorou E, Sepriano A, et al.: ASAS-EULAR recommendations for the management of axial spondyloarthritis: 2022 update. Ann Rheum Dis 2023; 82: 19–34; doi: 10.1136/ard-2022-223296.
- Sitzung «Biologika als First Line Therapie, ja oder nein?», Vortrag «… bei Spondylarthropathien erst nach NSAR, MTX & Co. – Contra», 129. Kongress der DGIM, 22.04.2023.
- Sieper J, Lenaerts J, Wollenhaupt J, et al.: Efficacy and safety of infliximab plus naproxen versus naproxen alone in patients with early, active axial spondyloarthritis: results from the double-blind, placebo-controlled INFAST study, Part 1. Ann Rheum Dis 2014; 73: 101–107; doi: 10.1136/annrheumdis-2012-203201.
InFo RHEUMATOLOGIE 2023; 5(1): 24–26
