Positioning Filgotinib in the Treatment Algorithm of Moderate to Severe Ulcerative Colitis

D’Amico, Ferdinando; Magro, Fernando; Peyrin–Biroulet, Laurent; Danese, Silvio

doi:10.1093/ecco-jcc/jjab206

Cited by 25 publications

(9 citation statements)

References 52 publications

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“…These studies are still ongoing, but in an interim analysis of pooled data from both studies for the primary endpoint, at week 13, 6.7% (8/120) and 8.3% (10/120) of participants treated with filgotinib 200 mg and placebo, respectively, experienced a ≥ 50% decrease from baseline in sperm concentration. 30,31 Strengths of the SELECTION trial included the simple dosing regimen, with no requirement for dose modification. Filgotinib has a low potential for drug-drug interactions, 32 and the oral administration route negates the need for clinic visits for infusion or injections.…”

Section: Discussionmentioning

confidence: 99%

“…Following observations of impaired spermatogenesis and histopathological changes to the testes and epididymis in rats and dogs during preclinical toxicology studies [ 29 ], 2 studies were designed to evaluate the potential effect of filgotinib on adult male semen parameters: 1 in men with moderately to severely active UC or Crohn’s disease (MANTA, ClinicalTrials.gov ID: NCT03201445), and the other in men with active rheumatic diseases (MANTA-RAy, ClinicalTrials.gov ID: NCT03926195). These studies are still ongoing, but in an interim analysis of pooled data from both studies for the primary endpoint, at week 13, 6.7% (8/120) and 8.3% (10/120) of participants treated with filgotinib 200 mg and placebo, respectively, experienced a ≥ 50% decrease from baseline in sperm concentration [ 30 , 31 ].…”

Section: Discussionmentioning

confidence: 99%

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Efficacy and safety of filgotinib as induction and maintenance therapy for Japanese patients with moderately to severely active ulcerative colitis: a post-hoc analysis of the phase 2b/3 SELECTION trial

et al. 2023

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Background/Aims: The safety and efficacy of filgotinib, a once-daily oral Janus kinase 1 preferential inhibitor, were evaluated in Japanese patients with ulcerative colitis (UC) in the phase 2b/3 SELECTION trial. Methods: SELECTION (NCT02914522) was a randomized, placebo-controlled trial comprising 2 induction studies and a maintenance study. Adults with moderately to severely active UC were randomized in induction study A (biologic-naïve) or B (biologic-experienced) to receive filgotinib 200 mg, 100 mg, or placebo once daily for 11 weeks. Patients in clinical remission or Mayo Clinic score response at week 10 entered the 47-week maintenance study. Efficacy and safety outcomes were assessed in Japanese patients enrolled in Japan. Results: Overall, 37 and 72 Japanese patients were enrolled in Japan in induction studies A and B, respectively, and 54 entered the maintenance study. Numerically higher proportions of filgotinib 200 mg-treated than placebo-treated patients achieved clinical remission in induction study A (4/15 [26.7%] vs. 0/6 [0%]) and the maintenance study (5/20 [25.0%] vs. 0/9 [0%]), but not induction study B (1/29 [3.4%] vs. 1/14 [7.1%]). Both doses were well tolerated, and no new safety signals were noted. Herpes zoster was reported in 1 filgotinib 200 mg-treated patient in each of induction study A (2.3%, 1/44) and the maintenance study (5.0%, 1/20). Conclusions: These data, alongside those of the overall SELECTION population, suggest the potential of filgotinib 200 mg as a viable treatment option for Japanese patients with UC. Owing to small patient numbers, data should be interpreted cautiously.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Efficacy and safety of filgotinib as induction and maintenance therapy for Japanese patients with moderately to severely active ulcerative colitis: a post-hoc analysis of the phase 2b/3 SELECTION trial

et al. 2023

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“…A study is ongoing in UC to evaluate testicular safety and to resolve any concerns (NCT03201445). 66 Further studies will be needed to compare UPA and filgotinib and to define whether one drug is superior to the other.…”

Section: Discussionmentioning

confidence: 99%

Evaluating Upadacitinib in the Treatment of Moderate-to-Severe Active Ulcerative Colitis: Design, Development, and Potential Position in Therapy

Napolitano¹,

D’Amico²,

Ragaini³

et al. 2022

DDDT

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Upadacitinib is a selective small molecule that inhibits Janus kinase (JAK) type 1. This molecule is administrated orally and is currently approved for the treatment of rheumatoid arthritis, atopic dermatitis, and psoriatic arthritis. Upadacitinib has been approved by the United States Food and Drug Administration for the induction and maintenance therapy of moderate-to-severe ulcerative colitis (UC) and is under investigation by the European Medicines Agency. Data from two induction and two maintenance Phase III randomized controlled trials (RCTs) proved the efficacy of upadacitinib in achieving clinical and endoscopic remission in patients with moderate-to-severe UC, regardless of previous inadequate response to other biologic therapies. The most frequently reported adverse events in the induction trials were acne, creatine phosphokinase increase, nasopharyngitis, headache, and anemia, while in the maintenance studies nasopharyngitis, elevation of creatine phosphokinase, UC exacerbation, upper respiratory tract infection, arthralgia, and anemia were reported. A limited proportion of upadacitinib-treated patients experienced adverse events of special interest, like herpes zoster infections or thromboembolic events, indicating a reliable safety profile. The aim of this review is to summarize the available evidence on upadacitinib in UC providing useful insights about the positioning of this drug in the therapeutic algorithm.

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“…However in pharmacokinetic studies, an increased drug concentration was observed in patients with an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73m²; thus dose reduction in these patients is suggested. 83 More data pertaining to the effects on the kidneys of therapeutic agents used for managing IBD are needed (Table 2).…”

Section: Emerging Therapiesmentioning

confidence: 99%

Renal and Urological Disorders Associated With Inflammatory Bowel Disease

Kumar

Pollok

Goldsmith

2022

Inflammatory Bowel Diseases

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Renal and urinary tract complications related to inflammatory bowel disease (IBD) have been relatively understudied in the literature compared with other extraintestinal manifestations. Presentation of these renal manifestations can be subtle, and their detection is complicated by a lack of clarity regarding the optimal screening and routine monitoring of renal function in IBD patients. Urolithiasis is the most common manifestation. Penetrating Crohn’s disease involving the genitourinary system as an extraintestinal complication is rare but associated with considerable morbidity. Some biologic agents used to treat IBD have been implicated in progressive renal impairment, although differentiating between drug-related side effects and deteriorating kidney function due to extraintestinal manifestations can be challenging. The most common findings on renal biopsy of IBD patients with renal injury are tubulointerstitial nephritis and IgA nephropathy, the former also being associated with drug-induced nephrotoxicity related to IBD medication. Amyloidosis, albeit rare, must be diagnosed early to reduce the chance of progression to renal failure. In this review, we evaluate the key literature relating to renal and urological involvement in IBD and emphasize the high index of suspicion required for the prompt diagnosis and treatment of these manifestations and complications, considering the potential severity and implications of acute or chronic loss of renal function. We also provide suggestions for future research priorities.

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Positioning Filgotinib in the Treatment Algorithm of Moderate to Severe Ulcerative Colitis

Cited by 25 publications

References 52 publications

Efficacy and safety of filgotinib as induction and maintenance therapy for Japanese patients with moderately to severely active ulcerative colitis: a post-hoc analysis of the phase 2b/3 SELECTION trial

Efficacy and safety of filgotinib as induction and maintenance therapy for Japanese patients with moderately to severely active ulcerative colitis: a post-hoc analysis of the phase 2b/3 SELECTION trial

Evaluating Upadacitinib in the Treatment of Moderate-to-Severe Active Ulcerative Colitis: Design, Development, and Potential Position in Therapy

Renal and Urological Disorders Associated With Inflammatory Bowel Disease

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