Individual therapeutic DAS28-dcrit responses differentiate between effectiveness of rheumatoid arthritis therapies and reflect patient-reported outcomes: retrospective analysis of DAS28 responses in comparative tocilizumab studies.

Assessment of individual therapeutic responses provides valuable information concerning treatment benefits in individual patients. We evaluated individual therapeutic responses as determined by the Disease Activity Score-28 joints critical difference for improvement (DAS28-dcrit) in rheumatoid arthritis (RA) patients treated with intravenous tocilizumab or comparator anti-tumor necrosis factor (TNF) agents. The previously published DAS28-dcrit value [DAS28 decrease (improvement) ≥ 1.8] was retrospectively applied to data from two studies of tocilizumab in RA, the 52-week ACT-iON observational study and the 24-week ADACTA randomized study. Data were compared within (not between) studies. DAS28 was calculated with erythrocyte sedimentation rate as the inflammatory marker. Stability of DAS28-dcrit responses and European League Against Rheumatism (EULAR) good responses was determined by evaluating repeated responses at subsequent timepoints. A logistic regression model was used to calculate p values for differences in response rates between active agents. Patient-reported outcomes (PROs; pain, global health, function, and fatigue) in DAS28-dcrit responder versus non-responder groups were compared with an ANCOVA model. DAS28-dcrit individual response rates were 78.2% in tocilizumab-treated patients and 58.2% in anti-TNF-treated patients at week 52 in the ACT-ion study (p = 0.0001) and 90.1% versus 59.1% at week 24 in the ADACTA study (p < 0.0001). DAS28-dcrit responses showed greater stability over time (up to 52 weeks) than EULAR good responses. For both active treatments, DAS28-dcrit responses were associated with statistically significant improvements in mean PRO values compared with non-responders. The DAS28-dcrit response criterion provides robust assessments of individual responses to RA therapy and may be useful for discriminating between active agents in clinical studies and guiding treat-to-target decisions in daily practice.

Five-year Efficacy and Safety of Tocilizumab Monotherapy in Patients with Rheumatoid Arthritis Who Were Methotrexate- and Biologic-naive or Free of Methotrexate for 6 Months: the AMBITION Study.

OBJECTIVE: To report on the 5-year efficacy and safety results of the AMBITION (Actemra versus Methotrexate double-Blind Investigative Trial In mONotherapy) monotherapy study (ClinicalTrials.gov: NCT00109408, NCT00720798). METHODS: Patients with rheumatoid arthritis for whom biologics had not failed or who did not discontinue methotrexate because of lack of efficacy or tolerability were followed up for 5 years to assess the efficacy and serious adverse events (SAE) of tocilizumab (TCZ) monotherapy. RESULTS: Longterm efficacy results showed that efficacy was maintained or improved for up to 264 weeks in patients receiving TCZ monotherapy. Serious infection was the most frequent SAE; no new safety signals were reported. CONCLUSION: Longterm monotherapy with TCZ demonstrated continuing efficacy and safety.

The effects of intravaginal clindamycin and metronidazole therapy on vaginal mobiluncus morphotypes in patients with bacterial vaginosis.

OBJECTIVE: The objective of this study was to compare the effects of treatments for bacterial vaginosis (BV) on vaginal Mobiluncus morphotypes. STUDY DESIGN: Analyses were performed on Mobiluncus scores from similarly conducted studies evaluating clindamycin vaginal single-dose cream (CVSDC) or metronidazole vaginal gel (MVG) in 55 patients with BV and with Mobiluncus morphotypes at baseline. RESULTS: Both treatment groups demonstrated significant reductions in Mobiluncus score. However, the Mobiluncus score at test-of-cure was lower in the CVSDC than in the MVG group (P=0.0471). More patients in the CVSDC group than in the MVG group achieved microbiologic (57.5% vs. 26.7%; P=0.04), clinical (57.5% vs. 26.7%; P=0.04), and therapeutic cures of BV (45.0% vs. 20.0%; P=0.09). CONCLUSION: Clindamycin reduces vaginal Mobiluncus morphotypes to a greater extent than metronidazole in patients with BV; this correlates with a higher BV cure rate.

The effects of intravaginal clindamycin and metronidazole therapy on vaginal lactobacilli in patients with bacterial vaginosis.

OBJECTIVE: The purpose of this study was to determine the effects of 3 intravaginal antibacterial treatments on vaginal lactobacilli in patients with bacterial vaginosis (BV). STUDY DESIGN: Retrospective analyses were performed on Lactobacillus scores from 3 similar studies evaluating 2 2% clindamycin vaginal creams and 0.75% metronidazole gel at baseline and at 21 to 30 days in 408 patients with BV. Scores were compared using a 1-way global F test and McNemar's test. RESULTS: All groups had similar mean Lactobacillus scores at baseline (P = 0.37) and at 21 to 30 days (P = .71). The 3 groups were also comparable at both visits with respect to the distributions of scores within each group. In all groups, there was significant improvement in the percentages of patients with no lactobacilli present at 21 to 30 days compared with baseline (P < .0001 for all comparisons). CONCLUSION: Clindamycin and metronidazole promoted similar levels of restoration of vaginal lactobacilli at 21 to 30 days.

The influence of immunomodulatory diets on transplant success and complications.

BACKGROUND: Animal studies have shown that dietary supplementation with arginine and lipids containing the omega-3 and omega-9 fatty acids prolong allograft survival in animals receiving a short course of low-dose cyclosporine. They also reduce cardiovascular complications and infections in humans. METHODS: Adult renal transplant patients receiving standard immunosuppression were stratified according to gender, diabetic state, donor source (LD or CD), and first versus repeat transplant, and randomized to receive or not receive supplemental arginine and canola oil (containing both omega-3 and omega-9 fatty acids) twice daily. Patients were followed for a minimum of 3 years. RESULTS: Seventy-six patients were randomized to the supplement group (S) and 71 patients to the control group (C). Intent-to-treat analysis revealed that S patients had fewer post-30 day first rejection episodes (5.4%) when compared with the C group (23.7%) (P=0.01) and fewer post-30 day episodes of calcineurin inhibitor (CNI) drug toxicity (9.2% vs. 35.3%, P=0.003). S patients developed new onset diabetes mellitus (NODM) less frequently by 3 years (2.3% vs. 14.5%, P=0.04), had fewer cardiac events (5.0% vs. 17.1%, P=0.05), and fewer episodes of sepsis (6.5% vs. 18.7%, P=0.05). CONCLUSIONS: Dietary supplementation with L-arginine and canola oil is a safe, inexpensive, and unique treatment, which is associated with decreased rejection rates and CNI toxicity after the first month in renal transplant patients. Due to reductions in NODM and cardiac events, long-term benefits for patient survival may be particularly important.

Pretransplant recipient cytomegalovirus seropositivity and hemodialysis are associated with decreased renal allograft and patient survival.

BACKGROUND: Pretransplant systemic inflammation has been associated with decreased renal allograft survival, and infectious agents such as cytomegalovirus (CMV) may play a role. We hypothesized that pretransplant CMV seropositivity is a risk factor for decreased patient and allograft survival after cadaveric renal transplantation and that other factors believed to modulate systemic inflammation, such as dialysis modality, might act synergistically with CMV to decrease patient and allograft survival. METHODS: The United Network for Organ Sharing database was reviewed to identify all patients undergoing cadaveric renal transplantation in the United States from 1988 to 1997. Outcomes for CMV seropositive and seronegative recipients of organs from CMV seronegative donors were analyzed. Subgroup analysis was performed to identify any synergistic influence on outcome between CMV serostatus and known determinants of risk, including degree of human leukocyte antigen mismatch, pretransplant dialysis, and cold ischemia time. RESULTS: Of 29,875 patients who underwent transplantation, 12,239 were CMV seronegative and 17,636 were CMV seropositive. Patient survival was decreased by pretransplant seropositivity (relative risk [RR] 1.11, P =0.001). In addition, this group demonstrated worse overall allograft survival (RR 1.05, P =0.029), although this adverse effect disappeared when patients who died with a functioning graft were censored. Decreased allograft survival was most pronounced in patients who were on hemodialysis before transplantation (RR 1.62, P =0.004). CONCLUSIONS: Pretransplant CMV seropositivity is associated with decreased patient survival. Pretransplant CMV seropositivity and hemodialysis have a synergistic adverse effect on graft survival, independent of patient mortality. Additional studies are required to define mechanisms by which pretransplant CMV infection and dialysis modality may contribute to decreased allograft survival.

A comparison between recipients receiving matched kidney and those receiving mismatched kidney from the same cadaver donor.

The optimal allocation of cadaveric kidneys for transplantation with reference to human leukocyte antigen (HLA) match and sharing these organs to a distant center remains controversial. The current analysis was performed using the United Network for Organ Sharing (UNOS) database for cadaveric kidney transplants (Tx) between 1988 and 1997. The graft survivals of zero-mismatch (matched) kidneys with the mate (mismatched) kidneys were compared. There were 2385 donors and 4770 Tx. Significant differences in recipient demographics between matched and mismatched Tx were: fewer African-American race (AA) in the matched group (9.0% vs. 21.9%), higher number of previous Tx (25.5% vs. 14.8%) and elevated mean cold ischemia time (24.0 vs. 22.2 h). Post-Tx dialysis requirements were similar (22.8% vs. 24.1%, p = 0.62) and matched kidneys had to travel more distance (920 vs. 232 miles). Using a Cox model, the matched group had a decreased relative hazard of graft failure of 23.0% (p = 0.0002) or 35% (p < 0.0001) with and without censoring for death. There was significantly better graft survival in the matched recipients in all pairs except AA (matched) and non-AA (mismatched). For older donors (> or = 50 years, n = 1508), the matched grafts survival was marginally significant (p =0.05). Matched kidneys have improved survival compared with the mismatched kidneys despite the longer distance traveled. The benefit of mismatched transplants was predominantly seen in non-AA.