Patients with spondyloarthropathies (SpA) often suffer from extra-musculoskeletal manifestations (EMMs), which can also affect the gut [1, 2]. These multifaceted diseases with a complex clinical picture have both physiological and psychological effects [3, 4]. [3, 4]. Treatment must be individually tailored to the needs of those affected.
Inflammatory bowel diseases (IBD) such as Crohn’s disease (CD) and ulcerative colitis (UC) are among the most common EMMs associated with SpA [5]. In ankylosing spondylitis (AS), the prevalence of IBD is estimated at 5-10% and an increased risk of IBD has also been found in psoriatic arthritis (PsA) [2, 6, 7]. In addition, 25-49% of AS patients were found to have subclinical inflammation and 50-60% microscopic inflammation, i.e. non-symptomatic intestinal inflammation [1]. These prevalences suggest a link between the gut and joints and raise questions about the potential involvement of the gut in SpA [8].
Similar inflammatory signaling pathways in joints and intestines
The link between joints and the gut is thought to be based on similar inflammatory signaling pathways [2]. Interleukin (IL-)17 plays a key role in the inflammatory responses underlying IBD and SpA and at the same time appears to have a potential protective function in the gut [8, 9]. In addition, signaling pathways via IL-23 and T helper cells-17 (TH17) are probably involved in the immune defense of the mucosa and epithelial tissue repair [9]. In vitro studies have shown that IL-17 and the IL-17-producing γδ T cells play a protective role in the intestine [9]. New cases and exacerbations of IBD have also been observed in clinical trials with IL-17 inhibitors [10, 11]. However, other molecules such as Janus kinase (JAK) inhibitors can also be used for immunosuppression in inflammatory diseases. They act intracellularly and can thus modulate the response of a variety of proinflammatory cytokines involved in the development of intestinal inflammation [12]. Current data show that no IBD relapses were observed in AS patients treated with the JAK inhibitor RINVOQ® (upadacitinib) (15 mg/T) [13].
The treatment of SpA in EMMs
For patients with complex disease profiles, treatment should be tailored as closely as possible to their needs [14, 15]. It is therefore important to consider possible EMMs and pay attention to symptoms that may indicate IBD in addition to the rheumatic disease. In addition to the general condition and intestinal symptoms such as chronic diarrhea, abdominal pain or fecal incontinence, these include weight loss, anemia of unexplained cause and a higher than expected C-reactive protein (CRP) level [16, 17]. Preferred investigations for these symptoms include a colonoscopy including biopsies, magnetic resonance imaging (MRI) or a complete blood count [16, 17]. Other options include the measurement of fecal calprotectin, which can be influenced by the use of non-steroidal anti-inflammatory drugs, or an ultrasound examination [18, 19]. In individually tailored treatment, symptoms of active IBD are considered a contraindication to the use of IL-17 inhibitors [14]. In SpA patients, however, abdominal pain and gastrointestinal symptoms can always occur for reasons unrelated to IBD (abscesses, infections) [17]. If symptoms of IBD manifest, it is advisable to refer patients to gastroenterologists without delay. This also applies to clarification if the indications of IBD are not conclusive (Fig. 1) [20].
Figure 1: Practical considerations for the treatment of SpA patients with intestinal inflammation. EAM = extra-articular manifestations; NSAID = non-steroidal anti-inflammatory drugs. Adapted from [15-17].
New approval of RINVOQ® for Crohn’s disease and ulcerative colitis [21]
In addition to the approvals in rheumatology (rheumatoid arthritis [RA], PsA and AS) and atopic dermatitis (AD), the JAK inhibitor RINVOQ® is now also approved for the treatment of UC and CD in Switzerland* [21]. In contrast to rheumatic diseases, RINVOQ® is used in UC and CD as induction therapy (45 mg/T for 8 weeks [UC] or 12 weeks [CD]) and maintenance therapy (15 mg/T or 30 mg/T [UC & CD]) [21]. In the induction studies, patients in both indications showed a rapid response within a few days with a significant improvement in symptoms relating to bowel movement frequency and rectal bleeding [22, 23]. At week 52, 73 % (UC) resp. 60 % (CD) of bio-IR patients** treated with the higher dose of 30 mg/T RINVOQ® achieved clinical remission, compared to 8 % (UC) or 13 % (CD) with placebo [24, 25].
No new safety signals for RINVOQ® in ulcerative colitis and Crohn’s disease
In addition to rapid and sustained response, the placebo-controlled clinical UC and CD studies confirmed the favorable benefit-risk profile of RINVOQ® without any new safety signals, even at the higher doses (30 mg/T or 45 mg/T) [21, 24, 26]. Herpes zoster (15 and 30 mg), hepatic disorders (15 mg only) and neutropenia (30 mg only) occurred in a larger number of UC patients treated with RINVOQ® compared to placebo [27]. In contrast, side effects such as severe cardiovascular events, venous thromboembolism and malignant diseases were comparable to the placebo group in UC patients even at the higher dosage of 45 mg/T RINVOQ® in the induction phase and 30 mg/T RINVOQ® in the maintenance phase [27]. The safety profile in patients with Crohn’s disease taking RINVOQ® is also consistent with the known safety profile of RINVOQ® [21].
Conclusion
JAK inhibitors are used for immunosuppression in inflammatory diseases. They act intracellularly and can thus modulate the response of a large number of pro-inflammatory cytokines involved in the development of intestinal inflammation [12]. The rapid and sustained remission as well as the favorable benefit-risk profile of RINVOQ® have also been confirmed in the two IBD indications UC and CD [21]. Practicing rheumatologists should monitor IBD as a possible EMM and consult a gastroenterologist if symptoms manifest [20].
* Indications/possible applications at www.swissmedicinfo.ch
** bio-IR: Patients who had an inadequate response to treatment with a biologic prior to RINVOQ® therapy, i.e. insufficient response, loss of response or intolerance to ≥1 biologic.
Brief technical information RINVOQ®
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The references can be requested by professionals at medinfo.ch@abbvie.com.
This article was produced with the financial support of AbbVie AG, Alte Steinhauserstrasse 14, 6330 Cham.
This article has been released in German.
Text: Dr. sc. nat. Katja Becker
CH-RNQ-240014 08/2024
