Additional file 2: of Effect of subcutaneous tocilizumab treatment on work/housework status in biologic-naĂŻve rheumatoid arthritis patients using inverse probability of treatment weighting: FIRST ACT-SC study

Overall baseline demographic and clinical characteristics of each group in the modified intention-to-treat set (unadjusted, adjusted). (DOCX 25 kb

Additional file 1: of Effect of subcutaneous tocilizumab treatment on work/housework status in biologic-naĂŻve rheumatoid arthritis patients using inverse probability of treatment weighting: FIRST ACT-SC study

Baseline demographic and clinical characteristics of patients in each group adjusted using inverse probability of treatment weighting in the modified intention-to-treat set (paid worker, house worker). (DOCX 22 kb

Discovery of Novel Indazole Derivatives as Highly Potent and Selective Human β₃‑Adrenergic Receptor Agonists with the Possibility of Having No Cardiovascular Side Effects

Novel indazole derivatives were prepared and evaluated for their biological activity and cardiovascular safety profile as human β₃-adrenergic receptor (AR) agonists. Although the initial hit compound <b>5</b> exhibited significant β₃-AR agonistic activity (EC₅₀ = 21 nM), it also exhibited agonistic activity at the α_1A-AR (EC₅₀ = 219 nM, selectivity: α_1A/β₃ = 10-fold). The major metabolite of <b>5</b>, which was an oxidative product at the indazole 3-methyl moiety, gave a clue to a strategy for improvement of the selectivity for β₃-AR agonistic activity versus α_1A-AR agonistic activity. Thus, modification of the 3-substituent of the indazole moiety effectively improved the selectivity to develop compound <b>11</b> with potent β₃-AR agonistic activity (EC₅₀ = 13 nM) and high selectivity (α_1A/β₃ = >769-fold). Compound <b>11</b> was also inactive toward β₁ and β₂-ARs and showed dose dependent β₃-AR mediated relaxation of marmoset urinary bladder smooth muscle, while it did not obviously affect heart rate or blood pressure (iv, 3 mg/kg) in anesthetized rats

Eligible patient population from the JMDC claims database (ABA-1L vs. ABA-2L+).

1L, first line; 2L+, second or later line; ABA, abatacept; df, degrees of freedom; JMDC, Japan Medical Data Center Inc; SD, standard deviation. aMcNemar’s chi-squared test or paired t-tests were used. bDisease duration (from date of initial diagnosis to ABA start date). (DOCX)</p

Scenario analyses: Differences in cost per patient achieving endpoints (ABA-1L vs. ABA-2L+).

Difference in costs per health gain PMPM (ABA-1L –ABA-2L+). Costs per health gain PMPM were calculated by dividing total costs by the number of responders, patients in CDAI or SDAI remission for each group. The more positive the vertical axis, the more cost-effective the ABA-2L+ was. 1L, first line; 2L+, second or later line; ABA, abatacept; ACR50, American College of Rheumatology response of at least 50% improvement; CDAI, Clinical Disease Activity Index; J-HAQ, Japanese version of Health Assessment Questionnaire; JPY, Japanese Yen; PMPM, per member per month; SDAI, Simplified Disease Activity Index.</p

Cost per responder and patient in remission–per member per month (ABA-1L vs. ABA-2L+).

Cost per responder and patient in remission–per member per month (ABA-1L vs. ABA-2L+).</p

ABA-1L vs. TNFi-1L: Patient characteristics of matched populations.

ABA-1L vs. TNFi-1L: Patient characteristics of matched populations.</p

Eligible patient population from the JMDC claims database (ABA-1L vs. TNFi-1L).

aPaired t-tests were used. bDisease duration (from date of initial diagnosis to ABA/TNFi start date). 1L, first line; ABA, abatacept; df, degrees of freedom; JMDC, Japan Medical Data Center Inc; SD, standard deviation; TNFi, tumour necrosis factor inhibitor. (DOCX)</p

One-way sensitivity analysis: ABA 1L vs. ABA 2L+.

Ten most influential parameters on the difference in total costs (JPY). Minimum: -719,173, 388; Maximum: 1,040,202,718; Base case: 1,941,292. 1L, first line; 2L+, second or later line; ABA, abatacept; MTX, methotrexate; NSAID, non-steroidal anti-inflammatory drug. (DOCX)</p

Effectiveness from the IORRA database (ABA-1L vs. TNFi-1L).

1L, first line; ABA, abatacept; ACR50, American College of Rheumatology response of at least 50% improvement; CDAI, Clinical Disease Activity Index; IORRA, Institute of Rheumatology, Rheumatoid Arthritis; J-HAQ, Japanese version of Health Assessment Questionnaire; SDAI, Simplified Disease Activity Index; TNFi, tumour necrosis factor inhibitor. (DOCX)</p