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Therapy Selection in Difficult to Manage Spondyloarthritis
Speaker: Dr. Dennis McGonagle – Leeds Institute of Rheumatic & Musculoskeletal Medicine, St. James Hospital, UK
Key Highlights:
Diagnostic and Treatment Challenges:
Dr. McGonagle outlined the complexity of diagnosing and treating spondyloarthritis (SpA), emphasizing its immune heterogeneity. Unlike autoimmune diseases such as lupus, SpA has varying manifestations linked to enthesitis, biomechanical dysregulation, and cytokine pathways like IL-23 and TNF. He highlighted challenges in diagnosing SpA early, particularly when it is misclassified as mechanical back pain or PMR-like phenotypes. Enthesitis further complicates diagnosis due to tissue inaccessibility, making targeted therapies and imaging difficult.
Case-Based Insights:
A typical case of ankylosing spondylitis (AS) was discussed, where the patient had undergone multiple biologic switches (etanercept, adalimumab – 40 mg EOW), golimumab – 100 mg/month, secukinumab – 150 mg) without sustained improvement. Patient refused JAKI and discussion still ongoing for bimekizumab.
Dr. McGonagle pointed out the need for more nuanced therapeutic decision-making in refractory cases. He also emphasized that while imaging is essential in diagnosis, it has limitations, particularly in distinguishing between active disease and mechanical changes.
Emerging Therapeutic Strategies:
Dr. McGonagle presented new therapeutic strategies showing promise for SpA management:
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JAK Inhibitors: Drugs like tofacitinib and baricitinib target multiple cytokines, including IL-6, and show potential in treating enthesitis independently of TNF pathways.
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Combination Therapies: Combining TNF and IL-17 blockers has been challenging due to safety concerns like infections. However, preliminary studies in psoriatic arthritis (PsA) suggest potential in combining IL-23 inhibitors (e.g., guselkumab) with IL-17 blockers.
Lessons from Gastroenterology: Dr. McGonagle referenced combination therapy in inflammatory bowel disease (IBD), particularly with guselkumab and golimumab, which showed superior efficacy without added toxicity. This offers valuable insights into SpA treatment.
Dr. McGonagle explained a trial by Feagan G B et al. Between November 2018 and November 2021, 358 patients were screened, and 214 were assigned to combination therapy (n=71), golimumab monotherapy (n=72), or guselkumab monotherapy (n=71). At week 12, 83% of the combination therapy group showed a clinical response, compared to 61% for golimumab and 75% for guselkumab. At week 50, adverse events were most common in golimumab (76%) and combination therapy groups (63%). No deaths or malignancies occurred during the induction period, though tuberculosis and colon adenocarcinoma were reported after week 12.
Special Phenotypes:
Certain SpA patients initially present with PMR-like symptoms but later evolve into SpA. Dr. McGonagle highlighted the importance of re-evaluation in such cases and the need for tailored biologic therapies. He also discussed non-inflammatory SpA, where chronic pain persists without active inflammation, and stressed the importance of a multidisciplinary approach involving gabapentinoids, antidepressants, and psychological support.
Speaker mentioned a case, involves a young female with a classic presentation of polymyalgia rheumatica (PMR), but further evaluation revealed sacroiliitis and enthesitis, suggesting a misdiagnosis of spondyloarthritis (SpA) with a PMR phenotype. In their center, 26 similar cases were found, with half diagnosed within three months and the other half requiring longer diagnosis, potentially leading to biologics.
The second case describes a 58-year-old male with inflammatory bowel disease (IBD) diagnosed late after MRI enterography. He later developed back pain and was found to be B27 positive, with previous imaging showing fused joints. Despite being treated with azathioprine and adalimumab, the patient flared at 68 with Crohn's disease activity exacerbating the condition.
Predictors of Response:
Dr. McGonagle identified key predictors for treatment response in SpA:
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HLA-B27 Positivity: Strongly linked to therapeutic response and disease severity, particularly in axial SpA.
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MRI Findings: Bone marrow edema in MRI is correlated with better treatment outcomes, although its absence complicates management, especially in axial PsA where soft tissue inflammation may be underrecognized.
Dr. McGonagle concluded the session by advocating for humility in diagnosing and managing spondyloarthritis, given the complexities of the disease. He emphasized the importance of personalized treatment approaches and continued research to address refractory disease challenges, including the evolving therapeutic landscape.
American College of Rheumatology Convergence 2024, November 14–19, Washington, D.C
