Limits...
Rilonacept in the treatment of acute gouty arthritis: a randomized, controlled clinical trial using indomethacin as the active comparator.

Terkeltaub RA, Schumacher HR, Carter JD, Baraf HS, Evans RR, Wang J, King-Davis S, Weinstein SP - Arthritis Res. Ther. (2013)

Bottom Line: All treatment groups reported within-group pain reductions from baseline (P<0.0001).Although primary endpoint pain reduction was greater with rilonacept plus indomethacin (-1.55±0.92) relative to indomethacin alone (-1.40±0.96), the difference was not statistically significant (P=0.33), so formal comparison between monotherapy groups was not performed.Pain reduction over the 72-hour period with rilonacept alone (-0.69±0.97) was less than that in the other groups, but pain reduction was similar among groups at 72 hours.

View Article: PubMed Central - HTML - PubMed

ABSTRACT

Introduction: In phase-3 clinical trials, the interleukin (IL-1) blocker, rilonacept (IL-1 Trap), demonstrated efficacy for gout flare prevention during initiation of urate-lowering therapy. This trial evaluated rilonacept added to a standard-of-care, indomethacin, for treatment of acute gout flares.

Methods: Adults, aged 18-70 years, with gout presenting within 48 hours of flare onset and having at least moderate pain as well as swelling and tenderness in the index joint were randomized to subcutaneous (SC) rilonacept 320 mg at baseline plus oral indomethacin 50 mg TID for 3 days followed by 25 mg TID for up to 9 days (n = 74); SC placebo at baseline plus oral indomethacin as above (n=76); or SC rilonacept 320 mg at baseline plus oral placebo (n=75). The primary efficacy endpoint was change in pain in the index joint (patient-reported using a Likert scale (0=none; 4=extreme)) from baseline to the average of values at 24, 48 and 72 hours (composite time point) for rilonacept plus indomethacin versus indomethacin alone. Comparison of rilonacept monotherapy with indomethacin monotherapy was dependent on demonstration of significance for the primary endpoint. Safety evaluation included clinical laboratory and adverse event (AE) assessments.

Results: Patient characteristics were comparable among the groups; the population was predominantly male (94.1%), white (75.7%), with mean±SD age of 50.3±10.6 years. All treatment groups reported within-group pain reductions from baseline (P<0.0001). Although primary endpoint pain reduction was greater with rilonacept plus indomethacin (-1.55±0.92) relative to indomethacin alone (-1.40±0.96), the difference was not statistically significant (P=0.33), so formal comparison between monotherapy groups was not performed. Pain reduction over the 72-hour period with rilonacept alone (-0.69±0.97) was less than that in the other groups, but pain reduction was similar among groups at 72 hours. Treatment with rilonacept was well-tolerated with no reported serious AEs related to rilonacept. Across all groups, the most frequent AEs were headache and dizziness.

Conclusions: Although generally well-tolerated, rilonacept in combination with indomethacin and rilonacept alone did not provide additional pain relief over 72 hours relative to indomethacin alone in patients with acute gout flare.

Trial registration: ClinicalTrials.gov registration number NCT00855920.

Show MeSH

Related in: MedlinePlus

Change in pain from baseline. Data are mean change in pain of the index joint from baseline to pain averaged for the 24-, 48-, and 72-hour assessments for (A) the primary endpoint using a Likert scale (0 = no pain to 4 = extreme pain), and (B) using a numerical rating scale (NRS; 0 = no pain to 10 = extreme pain). SC, subcutaneous.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC3672764&req=5

Figure 2: Change in pain from baseline. Data are mean change in pain of the index joint from baseline to pain averaged for the 24-, 48-, and 72-hour assessments for (A) the primary endpoint using a Likert scale (0 = no pain to 4 = extreme pain), and (B) using a numerical rating scale (NRS; 0 = no pain to 10 = extreme pain). SC, subcutaneous.

Mentions: All treatment groups were observed to have significant reductions in pain from baseline when averaged at 24, 48 and 72 hours (P < 0.0001) and assessed using the Likert scale. However, the mean reduction in pain with rilonacept plus indomethacin, 1.55 points, was not statistically significantly greater than the mean reduction in pain with indomethacin alone, which was 1.40 points (least squares mean difference -0.14, 95% CI -0.44, 0.15, P = 0.333) (Figure 2A). Since the difference was not significant, formal comparison between pain reduction in the rilonacept monotherapy group, which was 0.69 points, and the indomethacin monotherapy group, which was 1.40 points, was not required. However, a separate ad hoc analysis for this comparison showed that the difference between indomethacin monotherapy and rilonacept monotherapy significantly favored indomethacin (P < 0.0001). Similar results were observed with the NRS; significant reductions from baseline were observed in each of the treatment groups (P < 0.0001), with pain reductions of 3.87 in the rilonacept plus indomethacin group, 4.33 in the indomethacin monotherapy group, and 1.81 in the rilonacept monotherapy group (Figure 2B). While the NRS change with rilonacept plus indomethacin was similar to that of indomethacin alone (P = 0.2533), the ad hoc analysis significantly favored indomethacin monotherapy relative to rilonacept monotherapy (P < 0.0001).


Rilonacept in the treatment of acute gouty arthritis: a randomized, controlled clinical trial using indomethacin as the active comparator.

Terkeltaub RA, Schumacher HR, Carter JD, Baraf HS, Evans RR, Wang J, King-Davis S, Weinstein SP - Arthritis Res. Ther. (2013)

Change in pain from baseline. Data are mean change in pain of the index joint from baseline to pain averaged for the 24-, 48-, and 72-hour assessments for (A) the primary endpoint using a Likert scale (0 = no pain to 4 = extreme pain), and (B) using a numerical rating scale (NRS; 0 = no pain to 10 = extreme pain). SC, subcutaneous.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3672764&req=5

Figure 2: Change in pain from baseline. Data are mean change in pain of the index joint from baseline to pain averaged for the 24-, 48-, and 72-hour assessments for (A) the primary endpoint using a Likert scale (0 = no pain to 4 = extreme pain), and (B) using a numerical rating scale (NRS; 0 = no pain to 10 = extreme pain). SC, subcutaneous.
Mentions: All treatment groups were observed to have significant reductions in pain from baseline when averaged at 24, 48 and 72 hours (P < 0.0001) and assessed using the Likert scale. However, the mean reduction in pain with rilonacept plus indomethacin, 1.55 points, was not statistically significantly greater than the mean reduction in pain with indomethacin alone, which was 1.40 points (least squares mean difference -0.14, 95% CI -0.44, 0.15, P = 0.333) (Figure 2A). Since the difference was not significant, formal comparison between pain reduction in the rilonacept monotherapy group, which was 0.69 points, and the indomethacin monotherapy group, which was 1.40 points, was not required. However, a separate ad hoc analysis for this comparison showed that the difference between indomethacin monotherapy and rilonacept monotherapy significantly favored indomethacin (P < 0.0001). Similar results were observed with the NRS; significant reductions from baseline were observed in each of the treatment groups (P < 0.0001), with pain reductions of 3.87 in the rilonacept plus indomethacin group, 4.33 in the indomethacin monotherapy group, and 1.81 in the rilonacept monotherapy group (Figure 2B). While the NRS change with rilonacept plus indomethacin was similar to that of indomethacin alone (P = 0.2533), the ad hoc analysis significantly favored indomethacin monotherapy relative to rilonacept monotherapy (P < 0.0001).

Bottom Line: All treatment groups reported within-group pain reductions from baseline (P<0.0001).Although primary endpoint pain reduction was greater with rilonacept plus indomethacin (-1.55±0.92) relative to indomethacin alone (-1.40±0.96), the difference was not statistically significant (P=0.33), so formal comparison between monotherapy groups was not performed.Pain reduction over the 72-hour period with rilonacept alone (-0.69±0.97) was less than that in the other groups, but pain reduction was similar among groups at 72 hours.

View Article: PubMed Central - HTML - PubMed

ABSTRACT

Introduction: In phase-3 clinical trials, the interleukin (IL-1) blocker, rilonacept (IL-1 Trap), demonstrated efficacy for gout flare prevention during initiation of urate-lowering therapy. This trial evaluated rilonacept added to a standard-of-care, indomethacin, for treatment of acute gout flares.

Methods: Adults, aged 18-70 years, with gout presenting within 48 hours of flare onset and having at least moderate pain as well as swelling and tenderness in the index joint were randomized to subcutaneous (SC) rilonacept 320 mg at baseline plus oral indomethacin 50 mg TID for 3 days followed by 25 mg TID for up to 9 days (n = 74); SC placebo at baseline plus oral indomethacin as above (n=76); or SC rilonacept 320 mg at baseline plus oral placebo (n=75). The primary efficacy endpoint was change in pain in the index joint (patient-reported using a Likert scale (0=none; 4=extreme)) from baseline to the average of values at 24, 48 and 72 hours (composite time point) for rilonacept plus indomethacin versus indomethacin alone. Comparison of rilonacept monotherapy with indomethacin monotherapy was dependent on demonstration of significance for the primary endpoint. Safety evaluation included clinical laboratory and adverse event (AE) assessments.

Results: Patient characteristics were comparable among the groups; the population was predominantly male (94.1%), white (75.7%), with mean±SD age of 50.3±10.6 years. All treatment groups reported within-group pain reductions from baseline (P<0.0001). Although primary endpoint pain reduction was greater with rilonacept plus indomethacin (-1.55±0.92) relative to indomethacin alone (-1.40±0.96), the difference was not statistically significant (P=0.33), so formal comparison between monotherapy groups was not performed. Pain reduction over the 72-hour period with rilonacept alone (-0.69±0.97) was less than that in the other groups, but pain reduction was similar among groups at 72 hours. Treatment with rilonacept was well-tolerated with no reported serious AEs related to rilonacept. Across all groups, the most frequent AEs were headache and dizziness.

Conclusions: Although generally well-tolerated, rilonacept in combination with indomethacin and rilonacept alone did not provide additional pain relief over 72 hours relative to indomethacin alone in patients with acute gout flare.

Trial registration: ClinicalTrials.gov registration number NCT00855920.

Show MeSH
Related in: MedlinePlus