No temporal relationship was observed between the occurrence of these opportunistic infections and administration of the Crenolanib investigational product (Fig. 1a). Nonserious adverse events of opportunistic infections were not specifically https://www.selleckchem.com/products/PF-2341066.html identified and categorized as such, but individual terms included tuberculosis, which was reported

as a nonserious adverse event in four subjects receiving placebo and no subjects receiving denosumab. Fig. 1 a Serious adverse events of opportunistic infections and relationship to timing of administration of investigational product. b Serious adverse events of cellulitis and erysipelas and relationship to timing of administration of investigational product. Denosumab subject 5 experienced a fatal adverse event associated with cellulitis. c Events of endocarditis and relationship to timing of administration of investigational product. Denosumab subjects 1 and 2 experienced serious adverse events of endocarditis;

denosumab subject 3 experienced a nonserious adverse event of endocarditis. Circles indicate denosumab injections; plus signs indicate placebo injections; rectangles indicate onset and duration of the adverse event Skin infections Serious adverse events of infections involving the skin occurred in 3 (<0.1%) placebo subjects and 15 (0.4%) denosumab subjects (P < 0.05; Table 3). These were not injection-site reactions. In the denosumab group, most of these skin BAY 73-4506 cell line infections were cellulitis or clinically diagnosed erysipelas involving the lower extremities that resolved with administration of common antibiotics.

The overall incidence of adverse events of cellulitis and erysipelas (i.e., FAD both serious and nonserious adverse events) was not significantly different between treatment groups (0.9% placebo, 1.2% denosumab) [8]. There was no temporal association between the onset of serious adverse events of cellulitis and erysipelas and duration of treatment or time since last dose of investigational product (Fig. 1b). Table 3 Incidence of serious adverse events of skin infection   Placebo (N = 3,876)a, n (%) Denosumab (N = 3,886)a, n (%) Serious adverse events of infection involving the skin 3 (<0.1) 15 (0.4)* Cellulitis and erysipelas 1 (<0.1) 12 (0.3)b Skin bacterial infection 0 (0) 2 (<0.1) Staphylococcal infection 1 (<0.1) 1 (<0.1) Infected skin ulcer 0 (0) 1 (<0.1)b Subcutaneous abscess 1 (<0.1) 0 (0) *P < 0.05 vs placebo aNumber of subjects who received ≥1 dose of investigational product bOne subject in the denosumab group experienced events of cellulitis and erysipelas and infected skin ulcer Cellulitis and erysipelas are usually caused by Streptococcus pyogenes, Staphylococcus aureus, and other gram-positive bacterial infections. In this study, serious adverse events of cellulitis and erysipelas were diagnosed clinically and not usually confirmed by culture. A positive S.