Consideration of confounders, accuracy of diagnosis, and disease severity in assessing the risk of inflammatory bowel disease in patients with psoriasis and psoriatic arthritis/ankylosing spondylitis beginning interleukin‐7 inhibitor treatment: comment on the article by Penso et al

Abstract

Jain et al acknowledge the increased efficacy of RTX for patients with PR3-ANCA-positive, relapsing disease. The ACR/VF Voting Panel considered all of these factors when developing the recommendation. As the recommendation is conditional, provider and patient-specific factors may influence the choice of therapy.A second issue raised by Jain et al is that treatment with intravenous (IV) pulse CYC is preferable to daily oral CYC because IV pulse CYC has less toxicity. Whether IV pulse or daily oral CYC is a "better" treatment continues to be an area of debate. While the toxicity of a single course of IV pulse CYC is less than that of daily oral CYC (1), the benefit of this difference is unclear, because patients treated with IV pulse CYC have a significantly higher rate of relapse compared to those treated with daily oral CYC (2), and may need additional treatment. A single course of CYC can also have impactful, long-term consequences, such as affecting ovarian reserve (3). Because the toxicity of CYC can be dependent on the cumulative dose, duration of therapy with daily oral CYC is now usually much shorter than previously employed (e.g., 3 months versus 6 months). The toxicity of daily oral CYC may also be mitigated with proactive monitoring strategies (e.g., obtaining blood cell counts every 1-2 weeks during treatment). Based on these considerations, it is difficult to determine whether IV pulse or daily oral CYC should be preferred. Since both are valid options, physician experience and patient preferences should guide the choice of treatment.The impact of treatment with RTX on COVID-19 infection and vaccine response is important to consider. Jain et al suggest that CYC is a "safer" medication than RTX during the COVID-19 pandemic. Currently, there are not sufficient data published to determine how outcomes of COVID-19 infection differ in patients treated with CYC compared to those treated with RTX. As a B cell-depleting agent, RTX is known to substantially affect antibody responses to COVID-19 vaccination. However, patients with GPA treated with CYC also develop substantial B cell lymphopenia, which can extend past discontinuation of CYC, and can also experience a reduction in B cell function (4,5). Thus, treatment with CYC may also impair vaccine responses. Because therapy with CYC or RTX to induce remission is typically given in conjunction with high-dose glucocorticoids, the relative safety of RTX or CYC use during the COVID-19 pandemic may not be easily determined.Cost is also an appropriate factor to consider in making treatment decisions. These guidelines are based on practice in the United States, and thus the recommendations may need to be adjusted by physicians in other countries based on several factors, including costs and drug availability.The comments of Jain et al highlight many of the unanswered questions that remain when considering treatment options for patients with AAV, as well as the challenges of treating these diseases during the COVID-19 pandemic. The published recommendations were devel...

Causal Association Between Inflammatory Bowel Disease and Psoriasis: A Two-Sample Bidirectional Mendelian Randomization Study

“…Evidence from meta-analyses and observational studies supports an underlying bidirectional relationship between psoriasis and inflammatory bowel disease (IBD), although mechanisms remain unclear (11,12). Many factors, such as common genetic susceptibility loci, clinical course, and immunologic features, are shared by psoriatic diseases and IBD (5,(13)(14)(15)(16), and IBD was considered a subsequent extra-articular manifestation of PsA which should be specially monitored in PsA patients according to the previous studies. However, basic and observational studies are susceptible to confounding factors, such as demographics or environmental exposure (17,18).…”