From the Guidelines
We should not stop biological agents in inherited autoinflammatory diseases without careful consideration, as discontinuation can lead to relapses in 60-74% of patients, occasionally within a few weeks to months of discontinuation, as suggested by observational studies 1. When considering the management of biological agents in inherited autoinflammatory diseases, it's crucial to prioritize the patient's quality of life, morbidity, and mortality. The primary approach involves targeted therapies that block specific inflammatory pathways.
Key Considerations
- The decision to stop or taper biological agents should be based on individual patient factors, including disease severity, treatment response, and patient preferences.
- Discontinuation of TNFi after achieving remission or low disease activity can result in relapses, and treatment with a biologic should be planned to be continued long-term, barring toxicities 1.
- Tapering of biologics, such as TNFi, could be considered in patients with prolonged stable disease, but this approach is not recommended as a standard practice due to limited evidence regarding maintenance of long-term remission 1.
Treatment Options
- For IL-1 mediated conditions, anakinra, canakinumab, and rilonacept are effective biologic therapies.
- For TNF-mediated conditions, etanercept, adalimumab, or infliximab may be effective.
- Tocilizumab, an IL-6 inhibitor, is useful for conditions with IL-6 overproduction.
Monitoring and Individualization
- Treatment should be individualized based on the specific disease, its severity, and patient characteristics.
- Regular monitoring for side effects, including increased infection risk, injection site reactions, and potential long-term complications, is essential. In summary, the management of biological agents in inherited autoinflammatory diseases requires careful consideration of the potential benefits and risks of discontinuation or tapering, as well as individualization of treatment based on patient factors and disease characteristics, as supported by the 2019 update of the American College of Rheumatology/Spondylitis Association of America/Spondyloarthritis Research and Treatment Network recommendations 1.
From the FDA Drug Label
- 1 Serious Infections KINERET treated NOMID and DIRA patients the risk of a disease flare when discontinuing KINERET treatment should be weighed against the potential risk of continued treatment.
The FDA drug label does not provide a direct answer to whether biological agents can be stopped in inherited Autoinflammatory diseases. However, it mentions that the risk of a disease flare when discontinuing KINERET treatment should be weighed against the potential risk of continued treatment in NOMID and DIRA patients 2.
- Key considerations:
- Weigh the risk of disease flare against the potential risk of continued treatment.
- No direct information is available on stopping biological agents in inherited Autoinflammatory diseases.
- Clinical decision:
- A conservative approach would be to not stop biological agents without careful consideration and monitoring of the patient's condition.
- The decision to stop treatment should be made on a case-by-case basis, taking into account the individual patient's risk factors and medical history.
From the Research
Treatment Options for Inherited Autoinflammatory Diseases
- Interleukin (IL)-1 blockade is effective in most autoinflammatory conditions, including Familial Mediterranean fever (FMF), tumor necrosis factor receptor-associated periodic syndrome (TRAPS), cryopyrin-associated periodic syndromes (CAPS), and mevalonate kinase deficiency (MKD) 3, 4, 5.
- In FMF, colchicine remains the treatment of choice, but IL-1 blockade is effective when colchicine fails 3.
- In CAPS, the beneficial effect of IL-1 blockade is sustained, and side-effects are limited 3, 4.
- Some patients with TRAPS and MKD have sufficient suppression of inflammatory symptoms with NSAIDs or corticosteroids, but IL-1 blockade appears effective in these conditions as well 3, 5.
Mechanisms of Autoinflammatory Diseases
- Autoinflammation is caused by indiscriminate activation of the immune system in an antigen-independent manner 6.
- The understanding of the molecular pathways involved in these disorders has shed new lights on the pattern of activation and maintenance of the inflammatory response and disclosed new molecular therapeutic targets 4.
- The study of the pathophysiological consequence of mutations in the cryopyrin gene (NLRP3) allowed the identification of intracellular pathways responsible for the activation and secretion of the potent inflammatory cytokine interleukin-1β (IL-1β) 4.
Emerging Trends and Future Directions
- The discovery that IL-1 is not only triggered by infectious danger signals but also by danger signals released from metabolically 'stressed' or even dying cells has extended the concept of autoinflammation to disorders such as gout, and those that were previously not considered inflammatory 5.
- Despite the tremendous success of IL-1 blocking therapy, the use of these agents in a wider spectrum of autoinflammatory conditions has uncovered disease subsets that are not responsive to IL-1 blockade, and urge the continued quest to characterize additional dysregulated innate immune pathways that cause autoinflammatory conditions 5.