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Background: Rheumatoid arthritis (RA) is an autoimmune disease characterized by symmetrical peripheral polyarthritis in the hands and/or feet, leading to long-term disability if not treated effectively. RA is preceded by a preclinical phase, in which genetically predisposed individuals accumulate environmental risk factors, and during which autoimmunity develops, followed by the emergence of non-specific signs and symptoms before arthritis becomes manifest. Early treatment in at-risk individuals – i.e. before the disease is fully established – has the theoretical potential to delay or prevent disease onset, with a positive impact on both patients' life and society. Objectives: We aimed to understand the feasibility of preventive treatment in at-risk individuals, taking into account recently performed studies and ongoing clinical trials, as well as patient perspectives. Methods: We performed a systematic literature review (SLR) on Medline and Embase, searching articles published between 2010 and 2021 with the following key-words: “Rheumatoid arthritis”, “arthralgia”, “pre-treatment” or “prevent”. Results: Our SLR identified a total of 1821 articles. Articles were independently screened by two researchers. A total of 14 articles were included after screening, and an additional 8 reports were manually included. We identified ten relevant clinical trials performed in at-risk individuals, or in individuals with undifferentiated inflammatory arthritis. Although no treatment was shown to prevent RA onset, early treatment with rituximab and abatacept delayed onset of full-blown RA, and both conventional and biological disease-modifying anti-rheumatic drugs (DMARDs) decreased disease-related physical limitations and increased DAS28-defined remission, at least temporarily. Conclusions: This SLR demonstrates that early treatment of at-risk individuals may be effective in delaying RA onset, thereby decreasing disease-related limitations in individuals in the pre-clinical phase of RA. Whether this may ultimately lead to prevention of RA remains to be determined.

Hyper-IgD syndrome (HIDS) is a rare, severe hereditary autoinflammatory disease characterised by periodic fevers, elevated serum IgD levels and a wide range of symptoms. Although a few randomised controlled trials have been performed in this disorder, there are no straightforward treatment protocols and none of the potential therapies are registered for this indication. We report a case of a young woman with severe HIDS who failed numerous therapies. Eventually, rational treatment with a monoclonal anti-interleukin 6 receptor antibody was initiated. This therapy resulted in an impressive clinical improvement and reduction in the number of hospital admissions per year. This case report underlines the difficulty of finding a suitable treatment for rare, severe inflammatory diseases. Furthermore, we show that treating patients with targeted therapies may result in clinical benefit for the patient, as well as simultaneously teach us more about the pathophysiology of these rare, relatively understudied diseases.

Patients with severe therapy-refractory immune-mediated inflammatory diseases (IMIDs) are increasingly treated with biologics. Since official practice guidelines for these rare diseases are lacking, these drugs are often prescribed off-label. However, treating physicians encounter difficulties and risks when prescribing drugs off-label. Access to these biologics for off-label indications is currently not well organized, which may result in suboptimal care. This also blocks innovation in patient care. In this article we introduce the recently initiated RUBRIC (Rational Use of Biologics in Refractory Immune-mediated inflammatory diseases Consortium) register. This national register documents the efficacy and safety of off-label biologic treatment in combination with the development of treatment protocols and practice guidelines. We believe that the results from this register will ultimately lead to a more evidence-based use of biologics in patients with rare IMIDs, which may also result in better access to these drugs. Ultimately, both the individual patient and the group as a whole will benefit