From: Interleukin-1β inhibitors for the management of acute gout flares: a systematic literature review
Author | Number of GFs | Severity of GFs or pain | Duration of GFs and/or time between GFs | Synovitis | Other outcomes |
---|---|---|---|---|---|
CAN (N = 3) | |||||
Schlesinger et al., 2011a [20] | NR | Primary endpoint: % of patients with no/mild pain was numerically greater in most CAN groups vs TA from 24 to 72 h; the difference was significant for the 150-mg group The reduction in pain intensity from BL was also greater for CAN 150 mg vs TA from 48 h to 7 d | NR | Primary endpoint: All treatments reduced visible inflammation in the target joint by 72-h. At 72-h, CAN 150 mg had a lower score for tenderness and swelling vs TA; the difference remained significant at 7 d. Erythema was absent in 74.1% (CAN 150 mg) and 69.6% (TA) at 72-h and in 96.3% (CAN 150 mg) & 83.9% (TA) at 7 d | NR |
Schlesinger et al., 2011b [21] | Primary endpoint: Mean GFs PP (least-squares mean [SE]; ANCOVA): CAN 25 mg: 0.5 (0.2) CAN 50 mg: 0.5 (0.2) CAN 100 mg: 0.2 (0.2) CAN 200 mg: 0.4 (0.2) CAN 300 mg: 0.2 (0.2) CAN q4wk: 0.7 (0.2) CLC 0.5 mg: 0.8 (0.1) Significant for CAN 100 mg and 300 mg vs CLC 0.5 mg | NR | Time to first GF (HR [95% CI]): CAN 25 mg: 0.6 (0.3‒1.0) CAN 50 mg: 0.3 (0.2‒0.7) CAN 100 mg: 0.3 (0.1‒0.6) CAN 200 mg: 0.4 (0.2‒0.7) CAN 300 mg: 0.3 (0.1‒0.6) CAN q4wk: 0.3 (0.2‒0.7) Average duration of GFs (least-squares mean [SD]): CAN 25 mg: 4.6 (1.0) CAN 50 mg: 3.7 (1.2) CAN 100 mg: 2.8 (1.4) CAN 200 mg: 3.6 (1.3) CAN 300 mg: 3.1 (1.3) CAN q4wk: 3.3 (1.2) CLC: 5.1 (0.6) | NR | Patients experiencing ≥ 1 GF (n [%]): CAN 25 mg: 15 (27.3) CAN 50 mg: 9 (16.7) CAN 100 mg: 8 (14.8) CAN 200 mg: 10 (18.5) CAN 300 mg: 8 (15.1) CAN q4wk: 9 (16.7) CLC: 48 (44.4) All CAN patients were significantly less likely to experience ≥ 1 GF vs CLC patients (OR: 0.22–0.47) |
Schlesinger et al., 2012 [19] | ≥ 1 GF: CAN: 16.0% TA: 35.8% (OR: 0.34) Mean number of new GFs: CAN: 0.19 TA: 0.51 (rate ratio: 0.37) ≥ 2 GFs: CAN: 2.7% TA: 11.4% Median time to new GFs: CAN: > 168 d TA: 131 d | Primary endpoint: Mean pain scores at 72 h: CAN: 25.0 mm TA: 35.7 mm MD: ‒10.7 mm (95% CI: ‒15.4 to ‒6.0) | CAN delayed time to first new GF and reduced new GF risk over the 12-wk period by 62% vs TA | 72 h (OR vs TA [95% CI]): Tenderness: CAN: 2.2 (1.5‒3.1) Swelling: CAN: 1.7 (1.2‒2.5) Erythema: CAN: 0.6 (0.4‒0.9) | Taking rescue medication: CAN: 37.3% (oral steroids: 11.1%) TA: 54.6% (oral steroids: 23.6%) |
ANK (N = 2) | |||||
Janssen et al., 2019 [16] | NR | Primary endpoint: Pain scores decreased to a similar extent in both groups. Estimated marginal mean difference between treatment arms: ‒0.13 points in favour of ANK. The upper 95% CI (-0.44 to 0.18) did not surpass the NI margin of 0.4 | NR | For all the secondary outcomes, pattern of change was similar for ANK and TaU over 5 d | During the first 7 d, numerically more patients in ANK (n = 20; 46.5%) vs TaU (n = 16; 35.6%), took pain-relieving medication. After 2 d, numerically more patients on ANK achieved ≥ 50% decrease in NRS pain scores (OR: 1.4; 95% CI: 0.5‒3.7) vs TaU. On day 3‒5, ORs were in favour for ANK (only significant on day 3) |
Saag et al., 2021 [18] | Treated for 1 GF: TA: n = 54 ANK 100 mg: n = 55 ANK 200 mg: n = 52 Treated for 2 GFs: TA: n = 17 ANK 100 mg: n = 23 ANK 200 mg: n = 21 Treated for 3 GFs: TA: n = 5 ANK 100 mg and 200 mg: n = 13 | Primary endpoint: Change in pain from BL to 24‒72 h after first GF (mean [95% CI]): TA: − 39.4 (− 46.8 to − 32.0) ANK 100 mg: − 41.8 (− 48.9 to − 34.8) ANK 200 mg: − 40.7 (− 47.9 to − 33.4) Pain intensity for the first GF at 6, 12, 18, 24, 36, 48, and 72 h and 5, 6, 7, and 8 d was similar in ANK and TA groups Across treatment arms, reduction in pain intensity for the second and third GF was similar to the first GF | Median time to pain resolution for the first GF: ANK total: 120.5 h TA: 167.5 h (HR: 1.3 [95% CI: 0.9‒1.9]) Median time to response: ANK total: 46.7 h TA 40 mg: 47.6 h (HR: 1.2 [95% CI: 0.8‒1.7]) Median time to onset of effect for the first GF: ANK total: 17.8 h TA: 22.3 h (HR: 1.1 [95% CI: − 0.8 to 1.6]) Resolution of pain by day 15: ANK total: 70 (63.6%) TA 40 mg: 36 (65.5%) | Mean physician assessment of tenderness and swelling at 72 h: ANK total: − 0.5 (95% CI: − 0.7 to − 0.2; significant) TA: − 0.3 (95% CI: − 0.6 to − 0.1) and was also better for swelling on day 8 (− 0.3 [95% CI: − 0.6 to − 0.1]) Significantly less presence of erythema was reported in ANK total vs TA group at 72 h (OR: 0.5 [95% CI: 0.2‒1.0]) | Between BL and day 15, 44.5% of patients in the ANK total group and 47.3% in the TA group received rescue medication |
RL (N = 5) | |||||
Mitha et al., 2013 [17] | Primary endpoint: Number of GFs at week 16: PBO: 101 RL 80 mg: 29 RL 160 mg: 28 RL 160 mg had significantly fewer GFs PP (0.3; 95% CI: 0.2‒0.5) vs PBO (1.2; 95% CI: 0.9‒1.6), a 72.6% rate reduction (95% CI: 58.4%‒82.0%) Wk-16 GF days PP: PBO: mean of 11.2 (95% CI: 6.6‒15.8) RL 80 mg: 4.3 (95% CI: 0.5‒8.1) RL 160 mg: 1.9 (95% CI: 0.6‒3.1) | Treatment with RL resulted in significantly fewer days PP with a pain severity score ≥ 5 vs PBO. For the 80-mg group, this reduction was from 4.3 d (95% CI: 2.6‒6.0) with PBO to 1.7 d (95% CI: 0.0‒3.5), and for RL 160 mg, the reduction was to 0.9 d (95% CI: 0.3‒1.5) | The estimated median time to first GF in the PBO group was 34 d, significantly earlier than for either of the RL groups. Median time could not be estimated as < 50% of RL patients reported a GF | NR | The RR of ≥ 1 GF over 16 wk: RL 80 mg: 0.5 (95% CI: 0.3‒0.7); risk reduction: 54.3% (95% CI: 30.8%‒69.9%) RL 160 mg: 0.4 (95% CI: 0.2‒0.6); risk reduction: 63.5% (95% CI: 41.9‒77.1) Patients with ≥ 1 GF: PBO: 56.1% RL 80 mg: 25.6% RL 160 mg: 20.5% Patients with ≥ 2 GFs: PBO: 32.9% RL 80 mg: 8.5% RL 160 mg: 6.0% |
Schumacher et al., 2012a [23] | Primary endpoint: Mean number of GFs PP: PBO: 0.8 (33 GFs) RL: 0.2 (6 GFs) 81% decrease in GFs with RL with decrease maintained at ext and FU Fewer GFs in RL groups as early as 4 wk | Days with pain score ≥ 5 PP (mean [SD]): PBO: 2.0 (4.5) RL: 0.2 (0.8) | GF at week 4: PBO: 26.2% RL: 4.9% Median time to first GF: PBO: 77 d RL: N/A GF days PP (mean [SD]): PBO: 5.2 (8.0) RL: 1.4 (5.2) | NR | Patients with ≥ 1 GF (n [%]): PBO: 19 (45.2) RL: 6 (14.6) |
Schumacher et al., 2012b [22] | Primary endpoint: Number of GFs over 16-wk: PBO: 84 RL 80 mg: 23 RL 160 mg: 17 Mean number of GFs PP: PBO: 1.1 (95% CI: 0.7–1.4) RL 80 mg: 0.3 (95% CI: 0.1–0.5) RL 160 mg: 0.2 (95% CI: 0.1–0.3) Reduction in GFs vs PBO: RL 80 mg: 73.0% (95% CI: 57.1–83.0%) RL 160 mg: 80.0% (95% CI: 66.3–88.1%) Observed as early as 4 wk | Days PP with pain severity score ≥ 5 (mean [95% CI]): PBO: 2.1 (1.4‒2.8) RL 80 mg: 0.9 (0.0‒1.7) RL 160 mg: 0.4 (0.1‒0.6) | GF days PP (mean [95% CI]): PBO: 5.5 (3.3‒7.7) RL 80 mg: 2.4 (0.0‒4.9) RL 160 mg: 1.0 (0.3‒1.6) | NR | Patients using rescue medication up to week 16: PBO: 54.4% RL 80 mg: 25.0% RL 160 mg: 23.5% RR for ≥ 1 GFs: RL 80 mg: 0.4 (95% CI 0.2–0.7) RL 160 mg: 0.4 (95% CI 0.2–0.6) Percentage of patients > 1 GFs: PBO: 31.6% RL 80 mg: 5.0% RL 160 mg: 3.8% |
Sundy et al., 2014 [24] | Mean number of GFs PP at week 16: RL: 70.3% reduction vs PBO: 1.7 (95% CI: 1.4‒2.0) to 0.5 [95% CI: 0.4‒0.6] ≥ 1 GF by week 16: PBO: 51.1% RL: 25.7% (49.6% reduction) ≥ 2 GFs by week 16: PBO: 34.7% RL: 11.7% (66.4% reduction) | NR | Median time to first GF: PBO: 87 d RL: N/A as < 50% of patients (25.7%) reported GFs Total number of GF days PP at week 16: PBO: 7.7 (95% CI: 6.4‒9.0) RL: 2.7 (95% CI: 2.2‒3.2, 64.9% reduction) | NR | At week 16, GFs PP with tophi (mean [SD]): PBO: 2.1 (2.9) RL: 0.9 (1.6) Without tophi: PBO: 1.6 (2.6) RL: 0.4 (0.9) |
Terkeltaub et al., 2013 [25] | NR | Primary endpoint: All groups had significant pain reductions from BL when averaged at 24-, 48- and 72 h RL + IND mean pain reduction (1.6 points) was not significantly greater than IND alone (1.4 points): least squares mean difference: ‒0.1 (95% CI: ‒0.4 to 0.2) The difference between IND and RL favoured IND | NR | NR | Patients taking rescue medication at > 24‒48 h: RL + IND: 3.0% IND: 4.3% Mean change in pain at 24, 48, and 72 h were similar between groups except IND alone was significantly superior to RL alone at all time points |