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Abstract
Background: Anemia is a condition that can cause symptoms such as fatigue, headaches, palpitations, shortness of breath during exertion, and depression. If left untreated, it can lead to a decrease in quality of life and shortened life expectancy.1) Anemia is frequently observed in patients with rheumatoid arthritis (RA), and various factors are cited as the cause, including not only inflammation due to RA but also gastrointestinal bleeding, chronic kidney disease, and side effects of anti-rheumatic drugs. One of the side effects of JAK inhibitors is anemia, which can be problematic for RA patients. Reports on anemia caused by JAK inhibitors in actual clinical practice are still scarce worldwide. Filgotinib (FIL) is a JAK inhibitor with high JAK1 selectivity, and it is known not to inhibit JAK2, which mediates the signal of erythropoietin. 2) In this study, we examined whether there were differences in the incidence of anemia in RA patients treated with each JAK inhibitor.
Objectives: To compare and examine the incidence of anemia in RA patients receiving JAK inhibitors at our hospital between patients being treated with FIL and patients with JAK inhibitors other than FIL (Non-FIL).
Methods: We divided 73 RA patients who had used four JAK inhibitors (Filgotinib, Tofacitinib, Baricitinib, Upadacitinib) since 2013 into FIL group (34 cases) and Non-FIL group (103 cases). Cases of hemorrhagic anemia were excluded. We conducted a retrospective investigation of the transition of Hemoglobin values (Hb) at 12 and 24 weeks after the start of treatment. In addition, we performed propensity score matching for age, sex, baseline Hb value, CRP value, serum creatinine value, presence or absence of anemia treatment, presence or absence of steroids or anti-rheumatic drugs, and history of treatment with bDMARDs/JAK inhibitors. Furthermore, we examined the discontinuation rate of JAK inhibitors in both groups due to anemia during the observation period using the Kaplan-Meier method.
Results: The mean age was 69.0 years in the Non-FIL group and 74.5 years in the FIL group, indicating that the latter was older. The Hb value at the start of use was significantly lower in the FIL group (10.6 g/dl) than in the Non-FIL group (11.8 g/dl). In addition, the FIL group had a significantly higher number of cases of prior treatment with bDMARDs or JAK inhibitors and use of anemia treatment drugs. The reasons for starting FIL were insufficient effectiveness of the previous treatment and anemia, in that order. There was no difference in CRP value or RA disease activity during the observation period in either group. In the FIL group, there was a statistically significant increase in Hb value at 12 and 24 weeks after the start of JAK inhibitor treatment (0-12 weeks +0.72 g/dl, 0-24 weeks +0.99 g/dl). Furthermore, the same result was obtained by analyzing using propensity score matching (P<0.05), indicating that anemia improved in the FIL group. On the other hand, the Hb value at 12 weeks after the start of treatment was significantly lower than that at the start of treatment in the Non-FIL group, but it had stopped decreasing by 24 weeks (Graph 1). Next, the discontinuation rate of JAK inhibitors in both groups due to anemia (0-48 weeks) was zero in the FIL group. In the Non-FIL group, seven cases were discontinued by 24 weeks, but the number of discontinuations thereafter was relatively small (Graph 2).
Conclusion: Filgotinib, which has high JAK1 selectivity, was confirmed to cause less anemia than other JAK inhibitors in actual clinical practice for RA treatment. Furthermore, anemia caused by JAK inhibitors is likely to occur within 24 weeks after the start of treatment, and it is considered necessary to observe this period carefully.
REFERENCES: [1] Iron deficiency anaemia: assessment, prevention, and control. A guide for programme managers. Geneva: World Health Organization; 2001.
[2] The safety of JAK-1 inhibitors: Rheumatology.60;ii24-ii30; 2021.
Acknowledgements: NIL.
Disclosure of Interests: None declared.
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