This paper presents a summary of the evidence review group (ERG) report into the clinical and cost-effectiveness of adalimumab for the treatment of moderate to severe plaque psoriasis based upon a review of the manufacturer's submission to the National Institute for Health and Clinical Excellence (NICE) as part of the single technology appraisal (STA) process. The submission's clinical evidence came from three randomised controlled trials comparing adalimumab with placebo, two extension studies and one ongoing open-label extension study. The studies were of reasonable quality and measured a range of clinically relevant outcomes. A higher proportion of patients on 40 mg adalimumab every other week achieved an improvement on the Psoriasis Area and Severity Index (PASI) of at least 75% (PASI 75) compared with placebo groups after 12 or 16 weeks of treatment, and there was a statistically significant difference in favour of adalimumab for the proportion of patients achieving a PASI 50 and a PASI 90. In a mixed treatment comparison, for each PASI outcome the probability of a response was greater for infliximab than for adalimumab, but the probability of response with adalimumab was greater than that with etanercept, efalizumab and non-biological systemic therapies. Adverse event rates were similar in the treatment and placebo arms and discontinuations because of adverse events were low and comparable between groups. The submission's economic model presents treatment effectiveness for adalimumab versus other biological therapies based upon utility values obtained from two clinical trials. The model is generally internally consistent and appropriate to psoriasis in terms of structural assumptions and the methods used are appropriate. The base-case incremental cost-effectiveness ratio for adalimumab compared with supportive care for patients with severe psoriasis was 30,538 pounds per quality-adjusted life-year. Scenario analysis shows that the model was most sensitive to the utility values used. Weaknesses of the clinical evidence included not undertaking a systematic review of the comparator trials, providing very little in the way of a narrative synthesis of outcome data from the key trials and not performing a meta-analysis so that the overall treatment effect of adalimumab achieved across the trials is unknown. Weaknesses of the economic model included that the assumptions made to estimate the cost-effectiveness of intermittent etanercept used inconsistent methodology for costs and benefits and there were no clear data on the amount of inpatient care required under supportive care. The NICE guidance issued as a result of the STA states that adalimumab is recommended as a treatment option for adults with plaque psoriasis in whom anti-tumour necrosis factor treatment is being considered and when the disease is severe and when the psoriasis has not responded to standard systemic therapies or the person is intolerant to or has a contraindication to these treatments.

RECORD STATUS: None CITATION: Stachnik J. Adalimumab. University HealthSystem Consortium (UHC). Drug Monograph. 2002

ANTECEDENTES: El adalimumab es un anticuerpo monoclonal anti-FNT alfa totalmente humano. Los estudios publicados indican que su uso en los pacientes con AR puede ser efectivo y seguro. OBJETIVOS: El objetivo de esta revisión fue evaluar la eficacia y la seguridad del adalimumab para el tratamiento de la AR. MÉTODOS DE BÚSQUEDA: Se hicieron búsquedas en las bases de datos electrónicas hasta agosto 2004: MEDLINE, CINAHL, EBM Reviews (CDSR, ACP Journal Club, DARE y CENTRAL) y Health STAR. Se realizaron búsquedas manuales en resúmenes de congresos y se estableció contacto con las compañías farmacéuticas para obtener datos no publicados adicionales de los ensayos publicados."Adalimumab" se buscó como palabra de texto ya que no está indizado actualmente. La búsqueda no se limitó por idioma, año de publicación o tipo de publicación. CRITERIOS DE SELECCIÓN: Todos los ensayos controlados aleatorios (ECA) o ensayos clínicos controlados (ECC) que comparen adalimumab solo o en combinación con FARME con placebo u otros FARME. OBTENCIÓN Y ANÁLISIS DE LOS DATOS: Dos revisores obtuvieron los datos de forma independiente en un formulario estandarizado y evaluaron la calidad metodológica del ensayo mediante criterios validados. Las medidas de resultado incluyeron las respuestas ACR y EULAR, el DAS 28 y los componentes de la respuesta ACR y los datos radiográficos. También se incluyeron datos de seguridad. Los datos continuos se informaron como diferencia de medias ponderada (DMP) con intervalo de confianza del 95% (IC del 95%), beneficio absoluto (BA) y diferencia relativa (DR). Los resultados dicotómicos se informaron como riesgo relativo (RR) con IC del 95%, diferencia de riesgo absoluto (DRA) o diferencia de riesgo (DR) con IC del 95% y número necesario a tratar (NNT) o dañar (NND). Cuando no se encontró heterogeneidad significativa, los datos se agruparon. RESULTADOS PRINCIPALES: Se incluyeron en esta revisión seis estudios con 2381 pacientes. SE HICIERON DOS COMPARACIONES: A. adalimumab por vía subcutánea (sc) + metotrexato (o FARME) versus placebo sc + metotrexato (o FARME). B. adalimumab sc en monoterapia versus placebo sc. En la comparación A, con 40 mg de adalimumab a semanas alternas, el RR para lograr una respuesta ACR 20 a las 24 semanas varió en los estudios incluidos de 1,52 a 4,63 y el NNT varió de 1,9 a 5,4. El RR (IC del 95%) para lograr una respuesta ACR 50 fue 4,63 (3,04 a 7,05) y el NNT fue 3,0 (IC del 95%: 2,0 a 6,0). El RR (IC del 95%) para lograr una respuesta ACR 70 fue 5,14 (3,14 a 8,41) y el número necesario a tratar fue 7,0 (IC del 95%: 5,0 a 13,0). A las 52 semanas, los RR (IC del 95%) para lograr una respuesta ACR 20, 50 y 70 fueron 2,46 (1,87 a 3,22), 4,37 (2,77 a 6,91) y 5,15 (2,60 a 10,22), con NNT de 2,9; 3,1 y 5,3; respectivamente. A las 52 semanas, 40 mg de adalimumab a semanas alternas y 20 mg por semana demoró significativamente la evolución radiológica incluido el índice de Sharp modificado, la puntuación de erosión y la puntuación del espacio articular (sólo con 40 mg a semanas alternas). En la comparación B, con 40 mg de adalimumab semanas alternas, los RR para lograr una respuesta ACR 20, 50 y 70 en las semanas 24/26 fueron 1,91 (1,17 a 3,10), 2,84 (1,58 a 5,12) y 7,33 (2,25 a 33,90) con NNT de 5,0 (IC del 95%: 3,0 a 9,0), 7,0 (4,0 a 20,0) y 9,0 (3,0 a 38,0), respectivamente. En la mayoría de los estudios y comparaciones analizadas no hubo diferencias significativas en los resultados de seguridad entre los grupos de adalimumab y control. El desarrollo de anticuerpos antinucleares positivos fue significativamente más frecuente en los pacientes que recibían adalimumab que en los pacientes que recibían placebo. Las infecciones graves fueron significativamente más frecuente en los pacientes que recibían adalimumab en sólo un estudio (Keystone 2004) con un RR (IC del 95%) de 7,64 (1,02 a 57,18) y un NND de 30,2. CONCLUSIONES DE LOS AUTORES: En base a los estudios revisados aquí, el adalimumab en combinación con metotrexato es eficaz y seguro para el tratamiento de la artritis reumatoide. 40 mg de adalimumab sc a semanas alternas y 20 mg por semana demora la evolución radiográfica a las 52 semanas. El adalimumab en combinación con FARME diferente al metotrexato también es eficaz y seguro, aunque se encuentran disponibles datos de un sólo estudio y el número de pacientes en cada grupo es pequeño. El adalimumab en monoterapia es eficaz y seguro para el tratamiento de la artritis reumatoide pero el tamaño del efecto es más pequeño que con el tratamiento combinado.

OBJECTIVE: To assess the efficacy and safety of adalimumab in the treatment of rheumatoid arthritis (RA). METHODS: A Cochrane systematic review was performed. The literature search, selection and assessment of the methodological quality of the studies, and the data extraction were performed according to the standard methodology of the Cochrane reviews. Outcome measures included American College of Rheumatology (ACR) and European League Against Rheumatism responses, Disease Activity Score 28 and components of the ACR response, and radiographic and safety data. Weighted mean difference and relative risk were used for reporting continuous and dichotomous data, respectively. Number needed to treat (NNT) or to harm (NNH) were estimated when appropriate. When significant heterogeneity was not found, data were pooled. RESULTS: Six studies with 2,390 patients were included in this review. With adalimumab 40 mg every other week (eow) + methotrexate versus placebo + methotrexate, the absolute risk differences to achieve an ACR20, ACR50, and ACR70 response at 52 weeks were 35%, 32%, and 19% with NNT of 2.9, 3.1, and 5.3, respectively. At 52 weeks, adalimumab 40 mg eow and 20 mg every week (ew) significantly slowed the radiological progression. With adalimumab 40 mg eow versus placebo, the absolute risk differences to achieve an ACR20, ACR50, and ACR70 response at 24/26 weeks were 23.64%, 15.31%, and 12.22% with NNT of 5.0, 7.0, and 9.0, respectively. In most of the analyzed studies and comparisons, there were no significant differences in safety outcomes between adalimumab and control groups. CONCLUSION: On the basis of studies reviewed here, adalimumab is efficacious in the treatment of RA. No serious adverse effects occurred.

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BACKGROUND: A favorable benefit-risk profile has been established for adalimumab, with up to 5 years of treatment in 13 clinical trials in patients with moderate to severe chronic plaque psoriasis. OBJECTIVE: The aim of this analysis was to assess the long-term safety of all adalimumab exposure in all psoriasis clinical trials. METHODS: A total of six sets of data were analyzed as follows: (i) all cumulative safety data from all exposure for all adalimumab-treated patients in the 13 clinical trials in moderate to severe psoriasis (All Adalimumab Treatment Population) through April 2007, November 2008, and November 2009, respectively; (ii) longitudinal data for 1403 patients treated with adalimumab 40 mg every other week (eow) dosing (Every Other Week Population) through June 2007 and April 2010; and (iii) data from placebo-controlled periods of clinical trials. Adverse events that occurred up to 70 days after the final dose of adalimumab were analyzed. RESULTS: During placebo-controlled periods, a total of 572 patients had 173.0 patient-years (PYs) of exposure to placebo and 1188 patients had 370.5 PYs of exposure to adalimumab. Adverse event incidence rates, expressed as events per 100 PYs (events/100 PYs), for placebo- and adalimumab-treated patients for serious adverse events were 7.52 and 8.64, and for serious infectious adverse events were 2.89 and 2.43, respectively. In the 2007, 2008, and 2009 All Adalimumab Treatment Population there were, respectively, 1819 patients (2424.7 PYs), 2197 patients (4351.9 PYs), and 3010 patients (4844.7 PYs), with serious adverse event incidence rates of 6.51, 7.22, and 8.36 events/100 PYs, and serious infectious adverse event rates of 1.32, 1.38, and 1.65 events/100 PYs. In the 2007 and 2010 Every Other Week Population (n = 1403), there were 1883.5 and 2854.1 total PYs of exposure, respectively, with serious adverse event incidence rates of 6.32 and 6.87 events/100 PYs, and serious infectious adverse event rates of 1.33 and 1.37 events/100 PYs, respectively. CONCLUSIONS: Multiple lines of evidence from a total of six sets of safety data, with treatment for up to 5 years, including results from all adalimumab-treated patients, and a subset of patients treated with 40 mg eow dosing, did not show evidence of cumulative toxicity, and showed adverse event rates that were generally stable or decreased with increased mean per-patient exposure.

RECORD STATUS: This is a bibliographic record of a published health technology assessment from a member of INAHTA. No evaluation of the quality of this assessment has been made for the HTA database. CITATION: Turner D, Picot J, Cooper K, Loveman E. Adalimumab for the treatment of psoriasis. Health Technology Assessment 2009; 13 (Suppl 2 Article 7): 49-54

RECORD STATUS: This is a bibliographic record of a published health technology assessment. No evaluation of the quality of this assessment has been made for the HTA database. CITATION: All Wales Medicines Strategy Group (AWMSG). Adalimumab (Humira®) Penarth: All Wales Therapeutics and Toxicology Centre (AWTTC), secretariat of the All Wales Medicines Strategy Group (AWMSG). AWMSG Secretariat Assessment Report Advice No. 2113. 2013

RECORD STATUS: None CITATION: Canadian Coordinating Office for Health Technology Assessment. Adalimumab and rheumatoid arthritis. Canadian Coordinating Office for Health Technology Assessment (CCOHTA). 2003

RECORD STATUS: None CITATION: National Institute for Health and Clinical Excellence. Adalimumab for the treatment of psoriasis. London: National Institute for Health and Clinical Excellence (NICE). Technology Appraisal Guidance 146. 2008