Data for all 306 patients who had at least one dose of secukinumab were collected; 124 (41%) patients had AS and 182 (59%) had PsA.
The baseline characteristics of the patients are shown in Table 1.
Seven patients (2.3%, n = 306) had confirmed IBD prior to starting secukinumab; six (4.8%, n = 124) of these had AS and one (0.5%, n = 182) had PsA. There were three patients with suspected IBD prior to starting secukinumab; two (1.6%) with AS and one PsA (0.5%).
From the 306 patients, 24 had a GIRAE during follow-up, of whom 18 patients had formal investigations undertaken. Twelve of 24 (50%) patients with GIRAE had an alternative diagnosis to IBD confirmed. Four cases were identified as definite IBD following GIRAE. For the six patients who did not undergo formal investigation, the primary rheumatologist did not feel further investigations necessary due to symptom resolution. The two remaining patients were reviewed by an IBD specialist and no further investigations were recommended. The breakdown of cases by rheumatic disease and according to definite, probable and possible events is shown in Table 2.
Secukinumab length of treatment varied between 1 month and 36 months. The majority of the GIRAE, 21 (87.5%, n = 24), occurred within the first year of treatment (Figure 1), the earliest being after 3 months.
Distribution of gastrointestinal events according to time after starting treatment
Fifteen of the 24 (63%) patients with GIRAE had AS and nine had PsA. The cumulative probability of secukinumab drug withdrawal due to GIRAE was higher for AS than PsA (Figure 2). There was a statistically significant difference for GIRAE between patients known to have AS vs PsA [age and sex hazard ratio (HR) = 2.8; P = 0.018; 95% confidence interval (CI): 1.2, 6.7]. Neither age (P = 0.341) nor sex (P = 0.225) were significant predictors of GIRAE. Prior IBD diagnosis was strongly predictive (HR = 14.1; P < 0.001; 95% CI: 5.9, 33.3) of GIRAE.
Cumulative probability of not having secukinumab drug withdrawal due to GIRAE
Four of 24 patients had GIRAE consistent with a definite IBD diagnosis, and all of these had a background of AS (Figure 3). With a total follow-up time of 331 patient-years, the incidence of IBD was 1.3 per 100 person-years (95% CI: 0.9, 2.0). Two of these patients were flares of known IBD (one CD and one UC) and two were de novo cases, developing IBD symptoms at 5 and 12 months treatment duration, respectively. Both de novo cases had switched from a TNFi (the only two switchers in the group with definite events). One patient diagnosed with CD required surgical treatment (drainage of a perianal abscess) and the other underwent medical treatment for UC. Both de novo cases had a normal faecal calprotectin level upon GIRAE investigation. All definite IBD cases stopped treatment with secukinumab because of GIRAE.
Distribution of diagnosed IBD cases and the gastrointestinal-related adverse events; CD: Crohn's disease; GIRAE: gastrointestinal-related adverse events; IBDU: IBD unclassified; UC: ulcerative colitis.
In total, seven of 24 GIRAE were probable IBD cases. Amongst these, secukinumab was interrupted in six patients. These included three AS and four PsA patients. In one AS patient, treatment was restarted and resulted in recurrence of symptoms and treatment was permanently ceased. In another AS patient with known IBD unclassified (IBDU), treatment was continued despite a flare that occurred at 29 months. One PsA and one AS patient commenced on secukinumab were known to have IBD at baseline (the PsA patient had an earlier bowel resection for CD).
GIRAE suggestive of possible IBD cases were described in 13 patients, eight AS and five PsA. In patients with AS, all continued secukinumab treatment; two eventually stopping due to treatment inefficacy. Of the patients with AS commencing secukinumab; one AS patient had a confirmed history of IBDU in whom symptoms resolved without discontinuation, another developed GIRAE 3 months after switching from a TNFi and a further patient continued secukinumab after treatment for chlamydia-related rectal lymphogranuloma venereum. Amongst patients with PsA, one patient with known pancolonic inertia underwent a defunctioning ileostomy complicated by increased stoma output and peristomal infection, one patient had diverticular disease and two patients were suspected of infective colitis (one had normal colonoscopy). Faecal calprotectin was checked in six patients. The level was raised in one case diagnosed with diverticular disease and normal for the remainder.
Five of the seven patients with a pre-existing diagnosis of IBD developed GIRAE after starting secukinumab (Figure 3). The two definite cases experienced IBD flares of UC and CD at 11 and 12 months, respectively, after starting secukinumab, both of whom had AS. Two cases (one PsA with CD, one AS with IBDU) had GIRAE suggestive of probable cases at 4 and 29 months, respectively. One patient, with AS and IBDU, experienced GIRAE suggestive of a possible case at 16 months after starting secukinumab. For all patients with definite IBD and one with GIRAE suggestive of probable disease, secukinumab was discontinued permanently. Of the remaining two patients who did not develop GIRAE on secukinumab, both had UC and had secukinumab treatment continued.
Faecal calprotectin was used as a screening test in 11/24 patients who developed GIRAE on secukinumab. It was raised in two cases (one definite and one possible case) and normal in the remaining nine samples.
Rheumatology. 2021;60(11):5233-5238. © 2021 Oxford University Press