**7.1.1 Golimumab (CNTO148)**

Golimumab is a human immunoglobulin G1K Moab binding both soluble and transmembrane forms of TNF-, thereby neutralizing their bioactivity by blocking the interaction with receptor (Kavanaugh et al., 2009; Xu et al., 2009).

In a study with 337 patients, the pharmacokinetics of subcutaneously administered golimumab (50 or 100 mg every 4 weeks) were analyzed (Xu et al., 2009) and the following golimumab pharmacokinetic parameters were found: apparent clearance = 1.38 ± 0.04 L per day, apparent volume of distribution = 24.9 ± 1.04 L and absorption rate constant = 0.908 ± 0.121 per day. Significant covariants on apparent clearance were identified as body weight, baseline C-reactive protein level and smoking habits. However, only body weight was found to be a significant covariant on apparent volume of distribution. In addition, golimumab concentrations in patients (50 mg golimumab every 4 weeks) not receiving MTX were 30% lower as compared with patients receiving MTX (Xu et al., 2009). So far, no possible explanation for the different effects of MTX on the serum golimumab concentrations has been provided (Xu et al., 2009).

A randomized, double-blind, placebo-controlled phase III multicenter study was conducted to evaluate the safety and efficacy of golimumab from week 0 to 20 in 405 patients with active PsA (Kavanaugh et al., 2009).

Active PsA was defined as at least three swollen joints and three tender joints as well as active plaque psoriasis with a qualifying lesion of at least 2 cm in diameter. Concomitant MTX, non-steroidal anti-inflammatory drugs (NSAIDs) and corticosteroids were permitted at stable doses.

A significant reduction in PASI 75 among patients receiving golimumab 50 or 100 mg at week 14 (40 and 58%) was observed when compared with patients receiving placebo (3%). PASI 75 scores in patients with golimumab (50 and 100 mg) further improved at week 24 in both golimumab groups (56 and 66%), whereas only 1% of patients in the placebo group reached a PASI 75 (Kavanaugh et al., 2009).

Golimumab significantly (*P* < 0.001) improved signs and symptoms of PsA compared with patients treated with placebo (Kavanaugh et al., 2009). An ACR 20 response at week 14 could be achieved in 51% of patients treated with golimumab 50 mg and in 45% of patients receiving golimumab 100 mg versus only 9% in the placebo group. At week 24, an ACR 20 response was observed in 52% in the golimumab 50-mg group and in 61% in the golimumab 100-mg group versus 12% in the placebo group (*P* < 0.001). ACR 50 and 70 responses were also significantly higher in both golimumab groups than in the placebo group. At week 104, 91.4% of patients in the 50-mg group and 73.1% in the 100-mg group achieved an ACR 20 (Kavanaugh et al., 2009). A good or moderate DAS 28 response was significantly (*P* < 0.001) more often achieved in the golimumab 50 and 100-mg recipients than in the placebo group at week 14 (66 and 67% vs. 24%) and at week 24 (64 and 78% vs. 24%) (Kavanaugh et al., 2009). Assessment of physical function and health-related quality of life were measured by the Health Assessment Questionnaire (HAQ) and Short Form 36 Health Survey (SF-36) and significantly improved in both golimumab groups compared with the placebo group (*P* < 0.001 for HAQ and SF-36 at all comparisons at week 24).Thus, in this study golimumab improved significantly the clinical signs and symptoms of PsA as well as the physical function and quality of life (Kavanaugh et al., 2009).

About the of safety of this treatment, Kavanaugh and coll. (Kavanaugh et al., 2009) reported that 8.6% of patients treated with golimumab shown a serious adverse event up to week 104: serious infectious adverse events comprised sepsis/cholecystitis and abscess formation. about the cancers registered: one basal cell carcinoma, one colon cancer and one small lung cell carcinoma in the golimumab 50-mg group. In the golimumab 100-mg group, three basal cell carcinomas, one prostate cancer and one small lung cancer occurred.

As for adverse events, infections of the upper respiratory tract and nasopharyngitis were most frequently reported.
