Treatment with SDZ-ADL, an Adalimumab Biosimilar, in Patients with Rheumatoid Arthritis, Psoriasis, or Psoriatic Arthritis: Results of Patient-Reported Outcome Measures from Two Phase III Studies (ADMYRA and ADACCESS).

BACKGROUND: SDZ-ADL (GP2017; Sandoz GmbH, Austria) is an EMA-/FDA-approved adalimumab biosimilar. The effect of SDZ-ADL on quality of life (QoL) and patient-reported outcomes (PROs) was assessed as part of two phase III studies, one in patients with moderate-to-severe chronic plaque psoriasis (PsO; ADACCESS) and the other in patients with rheumatoid arthritis (RA; ADMYRA). Additionally, ADACCESS included patients with psoriatic arthritis (PsA). METHODS: ADACCESS included 465 patients with PsO, whereas ADMYRA included 353 patients with RA. Both studies evaluated and confirmed equivalent efficacy, similar safety, and immunogenicity of SDZ-ADL with reference adalimumab (ref-ADL). A third of patients underwent multiple (four) treatment switches between study treatments starting at Week 17 (ADACCESS); all patients switched from ref-ADL to SDZ-ADL at Week 24 (ADMYRA). Assessed PROs included Dermatology Life Quality Index (DLQI) and EuroQol five-dimension health status questionnaire (EQ-5D-5L) in ADACCESS, Functional Assessment of Chronic Illness Therapy-Fatigue Scale (FACIT-Fatigue) score in ADMYRA, and Health Assessment Questionnaire-Disability Index (HAQ-DI) in both studies. RESULTS: In both studies, baseline scores for all PRO assessments were comparable between the two treatment groups. In ADACCESS, mean DLQI decreased from baseline in both groups, and the mean (standard deviation [SD]) percent reductions from baseline in DLQI were comparable between groups at Week 17 (SDZ-ADL, - 64.5 [80.3]; ref-ADL, - 70.6 [41.7]), which were sustained after the switch at Week 51 ('continued SDZ-ADL,' - 79.7 [36.2]; 'continued ref-ADL,' - 80.8 [44.6]; 'switched to SDZ-ADL,' - 70.7 [32.2]; 'switched to ref-ADL,' - 69.3 [49.6]). In ADACCESS, the proportion of patients with an EQ-5D-5L score of 1 (no problems) increased from baseline for all five dimensions in all treatment groups and was comparable between treatment groups at Week 51. In ADACCESS, in patients with PsA at baseline, mean (SD) HAQ-DI scores decreased from baseline in both treatment groups, and scores were comparable between groups at Week 17 (SDZ-ADL, 0.5 [0.6]; ref-ADL, 0.5 [0.6]) and after switching at Week 51 ('continued SDZ-ADL,' 0.4 [0.5]; 'continued ref-ADL,' 0.4 [0.6]; 'switched to SDZ-ADL,' 0.5 [0.8]; 'switched to ref-ADL,' 0.7 [0.6]). In ADMYRA, proportion of patients achieving HAQ-DI in the normal range (≤ 0.5) was comparable between treatment groups at Week 24 (SDZ-ADL, 37.8%; ref-ADL, 36.3%) and after switching at Week 48 ('SDZ-ADL,' 41.6%; 'ref-ADL/switched to SDZ-ADL,' 40.0%). In ADMYRA, mean FACIT-Fatigue scores increased from baseline in both treatment groups. At Week 24, mean (SD) percent change from baseline in the FACIT-Fatigue scores was 75.4 (135.5) in SDZ-ADL and 73.0 (96.3) in ref-ADL groups; the scores were sustained after switching at Week 48. CONCLUSION: Treatment with SDZ-ADL and ref-ADL resulted in comparable improvements in PROs as well as QoL scores across the three diseases, PsO, PsA, and RA. Switching between SDZ-ADL and ref-ADL had no negative impact on PROs across the reported period. CLINICAL TRIALS. GOV IDENTIFIER: NCT02744755, NCT02016105.

Subcutaneous Injection of Drugs: Literature Review of Factors Influencing Pain Sensation at the Injection Site.

The subcutaneous administration route is widely used to administer different types of drugs given its high bioavailability and rapid onset of action. However, the sensation of pain at the injection site might reduce patient adherence. Apart from a direct effect of the drug itself, several factors can influence the sensation of pain: needle features, injection site, volume injected, injection speed, osmolality, viscosity and pH of formulation, as well as the kind of excipients employed, including buffers and preservatives. Short and thin needles, conveniently lubricated and with sharp tips, are generally used to minimize pain, although the anatomic injection site (abdomen versus thigh) also affects the sensation of pain. Large subcutaneous injection volumes are associated with pain. In this sense, the maximum volume generally accepted is around 1.5 ml, although volumes of up to 3 ml are well tolerated when injected in the abdomen. Injected volumes of up to 0.5-0.8 ml are not expected to increase substantially the pain produced by the needle insertion. Ideally, injectable products should be formulated as isotonic solutions (osmolality of about 300 mOsm/kg) and no more than 600 mOs/kg have to be used in order to prevent pain. A pH close to the physiological one is recommended to minimize pain, irritation, and tissue damage. Buffers are frequently added to parenteral formulations to optimize solubility and stability by adjusting the pH; however, their strength should be kept as low as possible to avoid pain upon injection. The data available recommend the concentration of phosphate buffer be limited to 10 mM and that the concentration of citrate buffer should be lower than 7.3 mM to avoid an increased sensation of pain. In the case of preservatives, which are required in multiple-dose preparations, m-cresol seems to be more painful than benzyl alcohol and phenol.Funding: Sandoz SA.