Optimising the Therapeutic Interval for Biologics in Patients with Psoriasis.

In our clinical experience, more than half of patients do not present a complete response to biologic drugs, or drug loses its efficacy over time. Plasma determinations of drug and anti-drug antibodies levels are an objective tool for optimisation in these patients; however, established therapeutic ranges are not suitable, so the objective of this study was to study these patients and optimise their healthcare. We have made a retrospective, observational study, using data of plasma levels of drugs and anti-drugs antibodies of infliximab, adalimumab or Etanercept, we summarise all data and make a study of sensitivity, specificity, positive and negative predictive value on current therapeutic ranges. We have found a statistically significant association between subtherapeutic levels and therapeutic failure in psoriasis treated with infliximab and adalimumab. New ranges were found with higher sensitivity than the established ones, we propose 2-10 µg/mL therapeutic range for infliximab, 3-11 µg/mL for adalimumab, and 1-7 µg/mL for etanercept. In conclusion, levels of drug and anti-drug antibodies are a decisive tool for predicting therapeutic response. The current therapeutic ranges may have minimum values that are excessively high, owing to which lowering them significantly increases the sensitivity of the test in all cases, and negative predictive value in the case of etanercept. Further prospective studies are needed to prove the usefulness of these new ranges.

Uso de ustekinumab tras otras terapias biológicas en psoriasis moderada-grave: Resultados en salud en vida real a largo plazo / Use of ustekinumab after other biological therapies in moderate-severe psoriasis: Real long-term data

OBJETIVO: Ustekinumab se usa en psoriasis en placas moderada-grave con respuesta inadecuada a fármacos antifactor de necrosis tumoral α. Recientes estudios sostienen la escasez de resultados en vida real a largo plazo. El objetivo es evaluar la efectividad y seguridad de larga duración de ustekinumab en psoriasis en placas moderada-severa refractaria a dos fármacos antifactor de necrosis tumoral α. MÉTODO: Estudio descriptivo retrospectivo entre enero de 2010 y marzo de 2019. Se incluyeron pacientes con psoriasis en placas moderada-grave tratados previamente con al menos dos agentes biológicos antifactor de ne-crosis tumoral α. Las variables de efectividad fueron respuestas Psoriasis Area and Severity Index 90 y 75 a las 24, 48, 72 y 96 semanas. La seguridad fue valorada mediante reacciones adversas y suspensiones de tratamiento. RESULTADOS: Se incluyeron 36 pacientes. El 61% fueron varones. Ustekinumab fue usado tras dos fármacos antifactor de necrosis tumoral α en el 88,9% de los pacientes. Los agentes biológicos previos más frecuentes fueron infliximab (94,4%) y etanercept (91,7%). Se observó que, al menos, el 66,7% de los pacientes alcanzaron Psoriasis Area and Severity Index90 en las semanas 24, 48, 72 y 96. Se registraron reacciones adversas asociadas a ustekinumab en 6 pacientes. No hubo suspensiones. CONCLUSIONES: Ustekinumab ha demostrado ser efectivo y seguro a largo plazo según resultados de vida real en psoriasis en placas moderada-severa tras respuesta inadecuada a dos fármacos antifactor de necrosis tumoral alfa

OBJECTIVE: Ustekinumab is used in moderate-severe plaque psoriasis with inadequate response to anti-tumour necrosis factor α drugs. Recent studies support the need to assess real long-term data. The aim of this study was to evaluate the real long-term effectiveness and safety of ustekinumab in moderate-severe plaque psoriasis refractory to 2 anti-tumour necrosis factor α drugs. METHOD: Retrospective descriptive study from January 2010 to March 2019. The study included patients with moderate-severe plaque psoriasis previously treated with at least 2 anti-tumour necrosis factor α biologic drugs. The effectiveness endpoints were Psoriasis Area and Severity Index 90 and 75 response rates at weeks 24, 48, 72, and 96. Safety was assessed using adverse effects and treatment withdrawal. RESULTS: A total of 36 patients were included (men, 61%). Ustekinumab was used after treatment with 2 anti-tumour necrosis factor α drugs in 88.9% of patients. The biologic drugs most frequently administered prior to ustekinumab were infliximab (94.4%) and etanercept (91.7%). It was observed that at least 66.7% of patients reached Psoriasis Area and Severity Index 90 at weeks 24, 48, 72, and 96. Adverse effects were recorded in 6 patients. There were no treatment withdrawals. CONCLUSIONS: Ustekinumab showed real long-term effectiveness and safety in moderate-severe plaque psoriasis with inadequate response to 2 previous anti-tumour necrosis factor Alpha drugs

Use of ustekinumab after other biological therapies in moderate-severe psoriasis: Real long-term data.

OBJECTIVE: Ustekinumab is used in moderate-severe plaque psoriasis with  inadequate response to anti-tumour necrosis factor α drugs. Recent studies  support the need to assess real long-term data. The aim of this study was to  evaluate the real long-term effectiveness and safety of ustekinumab in  moderate-severe plaque psoriasis refractory to 2 anti-tumour necrosis factor α  drugs. METHOD: Retrospective descriptive study from January 2010 to March 2019. The study included patients with moderate-severe plaque psoriasis previously treated with at least 2 anti-tumour necrosis factor α biologic drugs. The effectiveness  endpoints were Psoriasis Area and Severity Index 90 and 75 response rates at  weeks 24, 48, 72, and 96. Safety was assessed using adverse effects and  treatment withdrawal. RESULTS: A total of 36 patients were included (men, 61%). Ustekinumab was  used after treatment with 2 anti-tumour necrosis factor α drugs in 88.9% of  patients. The biologic drugs most frequently administered prior to ustekinumab  were infliximab (94.4%) and etanercept (91.7%). It was observed that at least  66.7% of patients reached Psoriasis Area and Severity Index 90 at weeks 24,  48, 72, and 96. Adverse effects were recorded in 6 patients. There were no  treatment withdrawals. CONCLUSIONS: Ustekinumab showed real long-term effectiveness and safety in  moderate-severe plaque psoriasis with inadequate response to 2 previous anti- tumour necrosis factor α drugs.

Objetivo: Ustekinumab se usa en psoriasis en placas moderada-grave con  respuesta inadecuada a fármacos antifactor de necrosis tumoral α. Recientes  estudios sostienen la escasez de resultados en vida real a largo plazo. El objetivo es evaluar la efectividad y seguridad de larga duración de ustekinumab en  psoriasis en placas moderada-severa refractaria a dos fármacos antifactor de  necrosis tumoral α.Método: Estudio descriptivo retrospectivo entre enero de 2010 y marzo de  2019. Se incluyeron pacientes con psoriasis en placas moderada-grave tratados  previamente con al menos dos agentes biológicos antifactor de necrosis tumoral  α. Las variables de efectividad fueron respuestas Psoriasis Area and Severity  Index 90 y 75 a las 24, 48, 72 y 96 semanas. La seguridad fue valorada  mediante reacciones adversas y suspensiones de tratamiento.Resultados: Se incluyeron 36 pacientes. El 61% fueron varones. Ustekinumab fue usado tras dos fármacos antifactor de necrosis tumoral α en el  88,9% de los pacientes. Los agentes biológicos previos más frecuentes fueron  infliximab (94,4%) y etanercept (91,7%). Se observó que, al menos, el 66,7%  de los pacientes alcanzaron Psoriasis Area and Severity Index 90 en las semanas 24, 48, 72 y 96. Se registraron reacciones adversas asociadas a ustekinumab en  6 pacientes. No hubo suspensiones. Conclusiones: Ustekinumab ha demostrado ser efectivo y seguro a largo plazo  según resultados de vida real en psoriasis en placas moderada-severa tras  respuesta inadecuada a dos fármacos antifactor de necrosis tumoral α.

Cost-effectiveness of lenalidomide maintenance in patients with multiple myeloma who have undergone autologous transplant of hematopoietic progenitor cells.

The objective of this article is to analyze the ratio of cost-effectiveness and budgetary impact of lenalidomide treatment in patients with multiple myeloma who have undergone autologous transplant in Spain. The analyses were based on clinical trials CALGB 100104 and IFM 2005-02, from the perspective of the National Health System. The alternatives compared were the treatment with lenalidomide against maintenance without treatment (MwT). Efficiency measures used were years of life gained (YGs) and quality-adjusted life years (QALYs). According to the CALGB 100104 trial data, the average health costs of patients who were treated with lenalidomide for 120 months was €836,534.31 and without treatment was €528,963.63. The effectiveness of the lenalidomide group was 7.59YGs (5.72 QALY) against 6.58 of MwT (4.61 QALY). The incremental cost-utility ratio (ICUR) was €277,456.72/QALY and the incremental cost-effectiveness ratio was €303,191.05/YGs. From the analysis, the IFM2005-02 trial obtained 5.13 QALY in the lenalidomide group against the 4.98 QALY in the MwT group, with an ICUR of €1,502,780.55/QALY. In terms of budgetary impact, a range between 799 and 1452 patients susceptible to receive treatment with lenalidomide was assumed in Spain. In conclusion, the results show a high ICUR and budgetary impact, which adds uncertainty about the maximum prudent duration of the treatment.

Network meta-analysis of tofacitinib versus biologic treatments in moderate-to-severe rheumatoid arthritis patients.

WHAT IS KNOWN AND OBJECTIVE: Rheumatoid arthritis (RA) is an autoimmune disease characterized primarily by inflammation and pain in the joints. Tofacitinib is an oral drug recently approved for RA treatment; it inhibits Janus protein kinases (JAK) that reduces RA symptoms when conventional DMARDs do not trigger a response. This study aimed to compare the efficacy of biological DMARDs in monotherapy or combined with methotrexate in RA patients and compare the treatments. METHODS: We reviewed the literature for articles published up to June 2017, evaluating the efficacy and safety of the biological DMARDs indicated for RA in patients with inadequate responses to conventional DMARDs and naïve to biological DMARDs, in similar populations, considering ACR50 as the efficacy variable. The odds ratio (OR) and 95% confidence interval (CI) were calculated for each drug combination, and these parameters were transformed into differences in responses to assess the effectiveness of the alternative medicines. Equivalence therapeutic alternatives (ETA) were ensured to assess the possibility of considering these medications with equivalent efficacy. A network meta-analysis (NMA) was performed using Bayesian approaches and the fixed-effects model. RESULTS AND DISCUSSION: Twenty-seven randomized clinical trials (RCTs) that met the pre-established criteria were identified. The 95% CI of biological DMARDs was higher than that of placebo without methotrexate, except for certolizumab, golimumab-m, anakinra-m and adalimumab monotherapy. These DMARDs performed significantly better than the placebo, except for etanercept, certolizumab, tofacitinib and golimumab. Certolizumab-m was better than anakinra-m and adalimumab, and tocilizumab alone or combined with methotrexate was superior to adalimumab. Etanercept-m yielded a higher difference in responses compared with the other biological DMARDs, which presented more homogeneous responses, except for adalimumab and anakinra-m, which yielded worse results. None of the biological DMARDs displayed ETA to etanercept-m; however, they displayed ETA with certolizumab-m, except for adalimumab and anakinra-m. WHAT IS NEW AND CONCLUSION: All biological DMARDs used in combination with methotrexate, except for etanercept, anakinra, certolizumab and tocilizumab without methotrexate, were displayed ETA on using ACR50 at week 24 in patients naïve to biological DMARDs. Etanercept displayed a greater difference in responses, although the high uncertainty of the comparative results prevented the confirmation of the increased efficacy of this drug.