Author: Gianpiero Pescarmona
Date: 22/04/2008


Antibodies can be used as drugs whenever a very specific binding to a molecule is required.

  • Passive immunity is achieved through the transfer of ready-made antibodies in the form of human or animal serum, pooled immunoglobulin or monoclonal antibodies, into the patient
  • "Targeted" monoclonal antibody therapy is employed to treat diseases such as rheumatoid arthritis, multiple sclerosis, psoriasis, and many forms of cancer including non-Hodgkin's lymphoma, colorectal cancer, head and neck cancer and breast cancer.
    • Natalizumab is a humanized monoclonal antibody against the cellular adhesion molecule α4-integrin
    • Rituximab is a chimeric monoclonal antibody against the protein CD20, which is primarily found on the surface of B cells.
  • antibodies are proteins and therefore behave as antigens


In origine il ritiro di efalizumab

Secondo le indagini, quando, nel giugno 2009, il farmaco biologico efalizumab (Raptiva), di Merck Serono, viene ritirato dal commercio, uscendo dal progetto Psocare, l'azienda fa venire a mancare a Torello Lotti 200 mila euro per i quali si era impegnato su più fronti, comprese alcune borse di studio. Ecco così che il dermatologo, sempre a detta degli inquirenti, comincia a offrire i circa 200 pazienti prima curati con Raptiva alle altre aziende coinvolte (Janssen & Cilag, Wyeth Lederle, Schering Plough, Abbott, Novartis, Morgan Pharma): più denaro versavano le imprese, più cresceva il numero di pazienti trattati con il farmaco "preferito". Il denaro veniva versato dalle aziende farmaceutiche a società organizzatrici di convegni per pagare corsi ed eventi. Queste ultime, poi, riversavano parte degli introiti al resto dell'organizzazione.

Side Effects

Mieloma multiplo, bortezomib potenzia la terapia di induzione, 2010

Nei pazienti colpiti da mieloma multiplo la terapia di induzione Vtd, che prevede l'aggiunta di bortezomib al regime standard (talidomide più desametasone) prima del doppio trapianto di cellule staminali autologhe, migliora il tasso di risposte complete o quasi complete e rappresenta un nuovo standard terapeutico nei casi di malattia eleggibile al trapianto. Questa la conclusione di uno studio randomizzato di fase 3 del Gimema italian myeloma network, che comprende tra gli autori Michele Cavo e Michele Baccarani dell'Istituto di ematologia Seràgnoli, università di Bologna. In totale sono stati arruolati 480 pazienti con mieloma precedentemente non trattato: l'analisi intention-to-treat è stata condotta su 236 pazienti trattati con Vtd e 238 con talidomide più desametasone (Td). Dopo la terapia di induzione, una risposta completa o quasi completa è stata raggiunta in 73 pazienti (31%) del gruppo Vtd e in 27 pazienti (11%) del gruppo Td. Gli eventi avversi di grado 3-4 sono risultati significativamente più numerosi con Vtd rispetto a Td (56% vs 33%). Si è notata, inoltre, la comparsa più frequente di neuropatia periferica nei soggetti avviati alla terapia Vtd rispetto al regime di confronto (10% vs 2%; 23 pazienti vs 5). La risoluzione o il miglioramento della grave neuropatia periferica si sono registrati in 18 pazienti Vtd sui 23 casi osservati e in 3 pazienti Td su 5.



Adverse effects of biologics: a network meta-analysis and Cochrane overview.


Cochrane Database Syst Rev. 2011 Feb 16;2:CD008794.

BACKGROUND: Biologics are used for the treatment of rheumatoid arthritis and many other conditions. While the efficacy of biologics has been established, there is uncertainty regarding the adverse effects of this treatment. Since serious risks such as tuberculosis (TB) reactivation, serious infections, and lymphomas may be common to the biologics but occur in small numbers across the various indications, we planned to combine the results from biologics used in many conditions to obtain the much needed risk estimates.

OBJECTIVES: To compare the adverse effects of tumor necrosis factor blocker (etanercept, adalimumab, infliximab, golimumab, certolizumab), interleukin (IL)-1 antagonist (anakinra), IL-6 antagonist (tocilizumab), anti-CD28 (abatacept), and anti-B cell (rituximab) therapy in patients with any disease condition except human immunodeficiency disease (HIV/AIDS).

METHODS: Randomized controlled trials (RCTs), controlled clinical trials (CCTs) and open-label extension (OLE) studies that studied one of the nine biologics for use in any indication (with the exception of HIV/AIDS) and that reported our pre-specified adverse outcomes were considered for inclusion. We searched The Cochrane Library, MEDLINE, and EMBASE (to January 2010). Identifying search results and data extraction were performed independently and in duplicate. For the network meta-analysis, we performed mixed-effects logistic regression using an arm-based, random-effects model within an empirical Bayes framework.

MAIN RESULTS: We included 163 RCTs with 50,010 participants and 46 extension studies with 11,954 participants. The median duration of RCTs was six months and 13 months for OLEs. Data were limited for tuberculosis (TB) reactivation, lymphoma, and congestive heart failure. Adjusted for dose, biologics as a group were associated with a statistically significant higher rate of total adverse events (odds ratio (OR) 1.19, 95% CI 1.09 to 1.30; number needed to treat to harm (NNTH) = 30, 95% CI 21 to 60) and withdrawals due to adverse events (OR 1.32, 95% CI 1.06 to 1.64; NNTH = 37, 95% CI 19 to 190) and an increased risk of TB reactivation (OR 4.68, 95% CI 1.18 to 18.60; NNTH = 681, 95% CI 143 to 14706) compared to control.The rate of serious adverse events, serious infections, lymphoma, and congestive heart failure were not statistically significantly different between biologics and control treatment. Certolizumab pegol was associated with significantly higher risk of serious infections compared to control treatment (OR 3.51, 95% CI 1.59 to 7.79; NNTH = 17, 95% CI 7 to 68). Infliximab was associated with significantly higher risk of withdrawals due to adverse events compared to control (OR 2.04, 95% CI 1.43 to 2.91; NNTH = 12, 95% CI 8 to 28). Indirect comparisons revealed that abatacept and anakinra were associated with a significantly lower risk of serious adverse events compared to most other biologics. Although the overall numbers are relatively small, certolizumab pegol was associated with significantly higher odds of serious infections compared to etanercept, adalimumab, abatacept, anakinra, golimumab, infliximab, and rituximab; abatacept was significantly less likely than infliximab and tocilizumab to be associated with serious infections. Abatacept, adalimumab, etanercept and golimumab were significantly less likely than infliximab to result in withdrawals due to adverse events.

AUTHORS' CONCLUSIONS: Overall, in the short term biologics were associated with significantly higher rates of total adverse events, withdrawals due to adverse events and TB reactivation. Some biologics had a statistically higher association with certain adverse outcomes compared to control, but there was no consistency across the outcomes so caution is needed in interpreting these results.There is an urgent need for more research regarding the long-term safety of biologics and the comparative safety of different biologics. National and international registries and other types of large databases are relevant sources for providing complementary evidence regarding the short- and longer-term safety of biologics.

Lancet. 2011 Jun 28. [Epub ahead of print]
Teplizumab for treatment of type 1 diabetes (Protégé study): 1-year results from a randomised, placebo-controlled trial., 2011
Sherry N, Hagopian W, Ludvigsson J, Jain SM, Wahlen J, Ferry RJ Jr, Bode B, Aronoff S, Holland C, Carlin D, King KL, Wilder RL, Pillemer S, Bonvini E, Johnson S, Stein KE, Koenig S, Herold KC, Daifotis AG; for the Protégé Trial Investigators.
Massachusetts General Hospital, Boston, MA, USA.
Findings of small studies have suggested that short treatments with anti-CD3 monoclonal antibodies that are mutated to reduce Fc receptor binding preserve β-cell function and decrease insulin needs in patients with recent-onset type 1 diabetes. In this phase 3 trial, we assessed the safety and efficacy of one such antibody, teplizumab.

In this 2-year trial, patients aged 8-35 years who had been diagnosed with type 1 diabetes for 12 weeks or fewer were enrolled and treated at 83 clinical centres in North America, Europe, Israel, and India. Participants were allocated (2:1:1:1 ratio) by an interactive telephone system, according to computer-generated block randomisation, to receive one of three regimens of teplizumab infusions (14-day full dose, 14-day low dose, or 6-day full dose) or placebo at baseline and at 26 weeks. The Protégé study is still underway, and patients and study staff remain masked through to study closure. The primary composite outcome was the percentage of patients with insulin use of less than 0·5 U/kg per day and glycated haemoglobin A(1c) (HbA) of less than 6·5% at 1 year. Analyses included all patients who received at least one dose of study drug. This trial is registered with, number NCT00385697.

763 patients were screened, of whom 516 were randomised to receive 14-day full-dose teplizumab (n=209), 14-day low-dose teplizumab (n=102), 6-day full-dose teplizumab (n=106), or placebo (n=99). Two patients in the 14-day full-dose group and one patient in the placebo group did not start treatment, so 513 patients were eligible for efficacy analyses. The primary outcome did not differ between groups at 1 year: 19·8% (41/207) in the 14-day full-dose group; 13·7% (14/102) in the 14-day low-dose group; 20·8% (22/106) in the 6-day full-dose group; and 20·4% (20/98) in the placebo group. 5% (19/415) of patients in the teplizumab groups were not taking insulin at 1 year, compared with no patients in the placebo group at 1 year (p=0·03). Across the four study groups, similar proportions of patients had adverse events (414/417 [99%] in the teplizumab groups vs 98/99 [99%] in the placebo group) and serious adverse events (42/417 [10%] vs 9/99 [9%]). The most common clinical adverse event in the teplizumab groups was rash (220/417 [53%] vs 20/99 [20%] in the placebo group).

Findings of exploratory analyses suggest that future studies of immunotherapeutic intervention with teplizumab might have increased success in prevention of a decline in β-cell function (measured by C-peptide) and provision of glycaemic control at reduced doses of insulin if they target patients early after diagnosis of diabetes and children.

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