Effectiveness and safety of ustekinumab in bio-naïve Crohn’s disease patients: a multicentre observational retrospective study

Abstract

Background: Clinical trials have demonstrated the efficacy and safety of ustekinumab in Crohn’s disease (CD). However, more data are necessary on the effectiveness of ustekinumab in bio-naïve patients in real-life studies. Objectives: The aim of our study was to evaluate the effectiveness and safety of ustekinumab in patients with CD refractory or intolerant to conventional therapy and without previous exposure to biological drugs. Design: We performed a nationwide, observational, retrospective, multicentre study including patients with CD, in which ustekinumab was used as the first biological drug. Methods: The corticosteroid-free clinical and biological response and remission were analysed at weeks 16, 24, 52 and 72. Clinical remission was defined as Harvey–Bradshaw index ⩽ 4 and biological remission as a faecal calprotectin (FC) <250 mg/g and C-reactive protein (CRP) <5 mg/L. Moreover, the persistence of the treatment and any adverse events were assessed. Results: In all, 84 patients were included in the study, males and females were equally distributed, with a median age of 63 years [interquartile range (IQR): 51–75] and a median disease duration of 6.8 years [IQR: 3.6–17.0]. The majority (86.9%) of patients were treated with ustekinumab as monotherapy, without concomitant immunosuppressive medication. The proportion of patients in corticosteroid-free clinical remission or response at weeks 16, 24, 52 and 72 was 93.3% (56/60), 86.8% (46/53), 82.2% (37/45) and 71.4% (30/42), respectively. CRP returned to normal values in 47.6%, 43.2%, 50% and 52.4% of patients at weeks 16, 24, 52 and 72, respectively. Similarly, FC was normalized in 45.5%, 45.5%, 48.6% and 50% of patients at weeks 16, 24, 52 and 72, respectively. The cumulative probability of remaining on ustekinumab treatment was 84.8% (95% confidence interval: 73.3–91.6) after 72 weeks. Ustekinumab was discontinued in 10 patients (11.9%) within 72 weeks of follow-up. Reasons for discontinuing treatment were lack of response ( n = 4), adverse events ( n = 4) and death ( n = 2). There were no discontinuations because of stable remission. Conclusions: Ustekinumab was effective and safe in Spanish bio-naïve CD patients, showing a quicker and more durable response than obtained in patients with previous biological treatment. In this cohort of bio-naïve patients starting on ustekinumab, the average age was high. Plain language summary Effectiveness and safety of ustekinumab in Crohn’s disease patients not previously exposed to other biological therapies Evidence on the use of ustekinumab in biological naïve real-world patients is scarce. Here, we present real-world data evaluating the effectiveness and safety of ustekinumab in 84 bio-naïve patients from 17 Spanish hospitals. We report high rates of both clinical and biological remission. Moreover, after 1 year, 90.4% of patients remained being treated with ustekinumab. The safety profile of ustekinumab in these patient population was favourable. In conclusion, our results show that in patients with CD, ustekinumab could be considered as first-line therapy.

Ustekinumab in the Treatment of Inflammatory Bowel Diseases: Evolving Paradigms

“…Importantly, an independent association was observed between previous exposure to anti-TNF-α (HR, 0.72) and VDZ (HR, 0.65) and a lower probability of responding to UST [ 80 ]. A study conducted in Belgium reported a 12-month remission of nearly 74% [ 81 ], and a recent Spanish study of CD reported remission at weeks 16 and 52 of 93% and 82%, respectively [ 82 ]. These findings were confirmed by a Canadian trial, which reported clinical remission in 59% of bio-experienced and 79% of bio-naïve CD patients [ 83 ].…”

“…Other treatments are usually recommended for refractory patients or those with specific contraindications to anti-TNF-α drugs [ 108 ]. The real-life data for the use of UST in this setting are still scarce and limited by small sample sizes and large heterogeneity of therapy protocols/outcome definitions [ 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 35 , 45 , 47 , 48 , 55 , 61 , 62 , 63 , 68 , 69 , 70 , 71 , 72 , 74 , 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 , 85 , 86 , 87 , 88 , 89 , 91 , 92 , 93 , 94 , 95 , 96 , 97 , 98 , 99 , 100 , 101 , …”

“…Other treatments are usually recommended for refractory patients or those with specific contraindications to anti-TNF-α drugs [108]. The real-life data for the use of UST in this setting are still scarce and limited by small sample sizes and large heterogeneity of therapy protocols/outcome definitions [9][10][11][12][13][14][15][16][17][18][19][20][21]35,45,47,48,55,[61][62][63][68][69][70][71][72][74][75][76][77][78][79][80][81][82][83][84][85][86][87][88][89].…”

Intravenous ustekinumab maintenance treatment in patients with loss of response to subcutaneous dosing

“…In contrast, in bio-naive patients, clinical remission at 1 year was higher, 82.2%. 16 Similar to other biologic drugs, primary or secondary loss of response has been published with ustekinumab. In a recent meta-analysis, 17 it has been estimated that in CD patients, the annual risk of loss of response to ustekinumab and dose escalation among primary responders was 21% and 25% per person-year, respectively.…”