Clinical response, drug survival, and predictors thereof among 548 patients with psoriatic arthritis who switched tumor necrosis factor α inhibitor therapy: results from the Danish Nationwide DANBIO Registry.

OBJECTIVE: To describe the frequency of treatment switching and outcomes among patients with psoriatic arthritis (PsA) who switched tumor necrosis factor α inhibitor (TNFi) agents in routine care. METHODS: We conducted an observational cohort study based on the Danish nationwide DANBIO registry. Treatment outcomes were evaluated using the American College of Rheumatology criteria for 20% improvement (ACR20)/ACR50/ACR70, European League Against Rheumatism (EULAR) response criteria for good response, and the 28-joint count Disease Activity Score (DAS28) (remission). Kaplan-Meier and regression analyses were used for drug survival analyses and to identify predictors of outcome after treatment switching. RESULTS: Of 1,422 patients starting TNFi agents, 548 patients (39%) switched to a second biologic drug during up to 10 years of followup. Median followup was 2.3 years (interquartile range [IQR] 1.0-4.3 years). Switchers were more frequently women (56% versus 45%), had a shorter disease duration (3 versus 4 years), a higher median Health Assessment Questionnaire (HAQ) score (1.1 [IQR 0.6-1.6] versus 0.9 [IQR 0.5-1.4]), DAS28 (4.8 [4.0-5.7] versus 4.4 [3.6-5.2]), pain score on a visual analog scale (VAS) (65 mm [46-77] versus 62 mm [40-75]), and fatigue score on a VAS (69 mm [50-83] versus 64 mm [42-80] mm) (all P < 0.05 at start of first TNFi). During the first and second treatment, HAQ, DAS28, and VAS scores and C-reactive protein levels had decreased after 6 months (all P < 0.05), and median drug survival was 2.2 versus 1.3 years (P < 0.001). Lower fatigue score increased survival of the second TNFi. After switching, the proportions of patients achieving a sustained ACR20, ACR50, ACR70, EULAR good response, and DAS28 remission after 3-6 months were 22% (number needed to treat [NNT] 4.5), 13% (NNT 7.9), 5% (NNT 20), 19% (NNT 5.3), and 34% (NNT 2.9), respectively. Response rates were lower during the second treatment (all P < 0.01 versus first TNFi). At the 2-year visit, 47% of switchers had achieved an ACR20 response. No differences between drug-drug combinations were found. CONCLUSION: Thirty-nine percent of the patients with PsA switched TNFi agents. Response rates and drug survival were lower after switching; however, half of the switchers had an ACR20 response 2 years after starting the first TNFi.

Impact of HIV-1 reverse transcriptase polymorphism F214L on virological response to thymidine analogue-based regimens in antiretroviral therapy (ART)-naive and ART-experienced patients.

BACKGROUND: A negative association between the polymorphism F214L and type 1 thymidine analogue (TA) mutations (TAMs) has been observed. However, the virological response to TAs according to the detection of F214L has not been evaluated. METHODS: We studied 590 patients from EuroSIDA who started TA therapy for the first time as part of potent combination antiretroviral therapy (cART) and who were tested for genotypic resistance within the past 6 months. End points were median reduction in the week 24 viral load and time to virological failure (2 consecutive VL measurements >400 copies/mL after at least 6 months of the TA-containing cART). RESULTS: In ART-naive patients, the prevalence of F214L was 17%. By 48 months after starting TA-based cART, the proportion of patients who experienced virological failure was 16% in patients with 214L and 36% in those with 214F (P=.03). In a multivariable Cox regression model, the relative hazard of virological failure for patients with 214L compared with those with 214F was 0.22 (95% confidence interval, 0.07-0.72). In ART-experienced patients, results were similar, and larger differences in virological response associated with the detection of 214L versus F were observed in patients with M41L/T215Y and mixed TAM profiles detected before the initiation of cART. CONCLUSIONS: This study provides evidence that the detection of polymorphism F214L is associated with a favorable virological response to TA-based cART.

Risk of AIDS and death at given HIV-RNA and CD4 cell count, in relation to specific antiretroviral drugs in the regimen.

BACKGROUND: It is unknown whether the relationship between the HIV-RNA/CD4 cell count and risk of clinical disease continues to hold true for newer antiretroviral drugs approved without data from clinical endpoint trials. OBJECTIVE: : To determine and compare whether rate ratios of AIDS and death at given, latest HIV-RNA and CD4 cell counts levels were similar, regardless of which nucleoside pair and specific third drugs patients received as antiretroviral therapy. DESIGN: EuroSIDA observational cohort. A total of 9802 prospectively followed patients. METHODS: Analysis included patients taking combination antiretroviral therapy (CART) regimens containing two non-abacavir nucleosides plus a 'third drug' of a non-nucleoside reverse transcriptase inhibitor, a (possibly ritonavir boosted) protease inhibitor or abacavir. RESULTS: A total of 6814 patients contributed a total of 22 766.6 person-years of follow up. Median latest CD4 cell count was 353 x 10 cells/l, HIV-RNA 199 copies/ml. A total of 900 events of new AIDS or death were observed. AIDS/death rates for any given CD4 or HIV-RNA category were similar regardless of specific drugs being used. Adjusted rate ratios (RR) for individual drugs compared with indinavir (for which clinical endpoint trials are available) were all close to 1 and with relatively narrow 95% confidence intervals (CI); for example, nelfinavir RR, 0.99 (95% CI, 0.76-1.28); efavirenz RR, 0.83 (95% CI, 0.57-1.20); abacavir RR, 1.01 (95% CI, 0.64-1.60). Results were similar for different nucleoside pairs. CONCLUSIONS: The results indicate that AIDS/death rates for given CD4 cell count and HIV-RNA categories are similar, regardless of CART regimen being taken and provide reassurance that HIV-RNA and CD4 cell counts in individual patients receiving newer drugs have the same meaning, in terms of AIDS/death risk, regardless of specific antiretroviral regimen.