A Cochrane review included studies. Twelve studies (n=5 422) included measures of benefit, and 11 of them were pooled. Thirteen studies included information on harms (n=5 273). The duration of follow-up was from 12 to 52 weeks and the range of doses of certolizumab pegol varied from 50 to 400 mg given subcutaneously (sc). In phase III trials, the control was placebo plus methotrexate (MTX) in 7 studies and placebo in 5 studies. In the 2 Phase II trials the comparator was only placebo.
The approved dose of certolizumab pegol, 200 mg every other week, produced clinically important improvements at 24 weeks for the following outcomes (table ): American College of Rheumatology (ACR) 50% improvement (pain, function and other symptoms of RA), The Health Assessment Questionnaire (HAQ; scale 0 to 3, lower scores mean better function), proportion of participants achieving remission (Disease Activity Score (DAS) < 2.6), and radiological changes: erosion score (ES; not a clinically important difference). Serious adverse events (SAEs) were statistically but not clinically significantly more frequent for certolizumab pegol. There was a clinically significant increase in all withdrawals in the placebo groups (for all doses and at all follow-ups), and there was a clinically significant increase in withdrawals due to adverse events in the certolizumab groups (for all doses and at all follow-ups).
Clinically important differences for the patient-reported measures of disease activity, and for structural damage measures between placebo and certolizumab pegol were observed, in favour of certolizumab pegol (table| Outcome | Relative effect (95% CI) | Assumed risk - control | Corresponding risk - intervention (95% CI) | Participants (studies) | NNT/NNTH |
|---|---|---|---|---|---|
| *All doses of certolizumab pegol vs placebo ACR = American College of Rheumatology; HAQ = Health Assessment Questionnaire; DAS = Disease Activity Score | |||||
| ACR 50% improvement | RR 3.80 (2.42 to 5.95) | 87 per 1000 | 359 per 1000 (328 to 391) | 1 445 (5 studies) | 4 (3 to 5) |
| HAQ change from baseline Scale from: 0 to 3 | MD -0.35 (-0.43 to -0.26) | The mean HAQ change from baseline in the control groups was -0.13 | The mean HAQ change from baseline in the intervention groups was 0.35 lower (0.43 to 0.26 lower) | 1 268 (4 studies) | 8 (7 to 11) |
| Proportion of patients achieving DAS <2.6 (remission) | RR 2.94 (1.64 to 5.28) | 123 per 1000 | 216 per 1000 (194 to 247) | 2 420 (6 studies) | 8 (6 to 12) |
| Radiological changes: Erosion Scores (scale from 0 to 230). | MD -0.67 (-0.96 to -0.38) | The mean radiological changes: Erosion Scores (ES) in the control groups was 0.7 | The mean Radiological changes: Erosion Scores (ES) in the intervention groups was 0.67 lower (0.96 to 0.38 lower) | 714 (2 studies) | 6 (4 to 10) |
| All Withdrawals* | RR 0.47 (0.39 to 0.56) | 524 per 1000 | 231 per 1000 (203 to 291) | 5 200 (13 studies) | 3 (2 to 6) |
| Withdrawals due to adverse events* | Peto OR 1.45 (1.09 to 1.94) | 38 per 1000 | 52 per 1000 (40 to 73) | 5 236 (12 studies) | 58 (28 to 329) |
| Serious adverse events | Peto OR 1.47 (1.13 to 1.91) | 58 per 1000 | 85 per 1000 (59 to 120) | 3 927 (9 studies) | 33 (25 to 100) |
Clinical comment: A potential risk of serious adverse events, including hypertension and tuberculosis in susceptible individuals, needs to be borne in mind when considering certolizumab pegol.