Background/Purpose: IL-1 blocking therapy shows promise in the treatment of Behçet’s eye disease, but its effect on mucocutaneous manifestations is unknown.
Methods: 6 patients with Behçet’s disease as determined by International Study Group criteria and active oral or genital ulcers for ≥2 months were enrolled in this open label phase I/II study. 2 patients had a history of inactive uveitis (anterior, panuveitis). Study duration was 3 months with extension up to 16 months (range 4-16). All were treated with anakinra 100mg subcutaneous daily with the option to escalate dose to 200mg in partial responders after 1 month and 300mg after 6 months. Patients recorded the number and severity of oral and genital ulcers in daily diaries. The primary outcome was remission defined as no ulcers on physical exam for 2 consecutive monthly visits from months 3-6. Secondary outcomes included the number of ulcers, the number and severity of patient-reported ulcers, patient/physician global scores, and standardized disease activity scores.
Results: 2 of 6 patients achieved the primary outcome of remission from months 3-6. All but 1 had improvement in the number of oral ulcers at month 3 (primary endpoint). Mean number of oral ulcers at baseline, month 3 and month 12 were 3.3, 1.5 and 0.5 and mean number of genital ulcers were 0.8, 0 and 0. Over the entire study, patients reported ≥1 oral and ≥1 genital ulcer on 665 (66%) and 139 (14%) days, respectively. Non-statistically significant improvements were seen in secondary outcomes including physician and patient visual analog scores and scores for Behcet’s disease current activity form (BDCAF) patient index, and Behcet’s disease quality of life (BDQOL). Behcet’s syndrome activity scale (BSAS) showed significant changes at 3 and 9 months. (Table). Dose escalation to 200mg occurred in all patients prior to month 3 and was further increased in 3 to 300mg after month 6. 2 patients on baseline prednisone of 40mg and 20mg were tapered to 20mg and 0mg, respectively. On anakinra 200mg vs. 100mg, patients reported fewer days with oral ulcers (65% vs 74% days, p=0.02) and genital ulcers (10% vs 22% days, p<0.001) and milder ulcer severity (p<0.01). Increase of anakinra to 300mg did not result in fewer ulcers or milder ulcer severity. No ocular flares occurred during the study; however, 2 ocular flares (anterior uveitis, periorbital inflammation) occurred within a month after discontinuation of anakinra in the 2 patients with prior eye disease. Adverse events included a serious adverse event of pulmonary hypertension suspected prior to the study and frequent viral infections.
Conclusion: In this open-label pilot study, anakinra, at an optimal dose of 200mg daily, demonstrated partial efficacy in treatment of resistant oral and genital ulcers in Behçet’s disease. Organ-specific differential effects of IL-1 blockade are likely.
NCT01441076
Table – Mean (SD) Values for Disease Activity Measurements
|
|
Baseline (n=6) |
Month 1 (n=6) |
Month 2 (n=6) |
Month 3 (n=6) |
Month 6 (n=4) |
Month 9 (n=4) |
Month 12 (n=4) |
|
Oral ulcer number |
3.3 (0.8) |
1.5 (1.2) |
1.5 (1.4) |
1.5 (2) |
0.8 (1) |
0.4 (0.5) |
0.5 (0.6) |
|
Genital ulcer number |
0.8 (1.3) |
0.5 (0.8) |
0.3 (0.8) |
0 (0) |
0 (0) |
0 (0) |
0 (0) |
|
Physician global VAS (0-100) |
26.5 (25.9) |
19 (14.3)
|
19.8 (8.3) |
14.5 (7.3) |
12 (8) |
9 (9.8) |
10 (5.3) |
|
Patient global VAS (0-100) |
63.7 (28.9) |
39.5 (32.1) |
59.4 (25.9) |
59.5 (32.5) |
49.3 (40.1) |
28.3 (18.3) |
46 (72.5) |
|
BDCAF (0-12) |
6.7 (2.3) |
6.2 (1.9) |
5.5 (2.2) |
5.8 (2.8) |
5 (0.8) |
4.3 (2.2) |
5.3 (1.7) |
|
BSAS (0-100) |
50.1 (20.2) |
34 (13.7) |
42.6 (14) |
26.9 (16.1) * |
21.6 (18.7) |
21.9 (9.3)* |
41 (21) |
|
BDQOL (0-30) |
15.3 (5) |
10.2 (7.3) |
11 (8.1) |
12.5 (10.3) |
10.3 (10.9) |
7.7 (5.7) |
11.7 (4.9) |
* p < 0.05 paired t-test from baseline
Disclosure:
P. C. Grayson,
None;
Y. Yazici,
Celgen, BMS,genentech,
2;
E. Novakovich,
None;
E. Joyal,
None;
R. T. Goldbach-Mansky,
None;
C. H. Sibley,
None.
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