Psoriasis Update: 2012 Part 2

POINT: COUNTERPOINT – MACE and Its Relationship to IL 12/23 Inhibition

Ken Gordon, MD

Dr. Gordon presented a counterpoint to Dr. Leonardi’s perspective regarding the association of IL 12/23 inhibition with MACE events. Dr. Gordon feels that while there is not a definitive answer at this time regarding the association it is important to discuss both sides to the story.

When a dermatologist thinks about the data that has been presented, specifically on ustekinumab, one needs to consider whether IL 12/23 has a true effect on MACE events. There are two approaches to this: 1. Observe the world, here is the observation and it needs to be explained; 2. Utilize the Scientific Method.

In the context of IL 12/23 and looking at MACE events, there has been an inductive moment, and that is the paper that Dr. Leonardi referred to, i.e., the Meta-analysis regarding IL 12/23.

In reviewing the overall conclusions that were presented in the meta-analysis of the association of IL 12/23 inhibition and MACE events, Dr. Gordon concluded that at least in the case of ustekinumab, there may not really be an answer. It is important to remember that meta-analyses have two required aspects in order for them to be effective: 1. The trials have to be similar in structure; 2. The intervention that is used has to be similar. In combining the trials using ustekinumab with those using briakinumab one can see that despite their effect on IL 12/23 these drugs are actually quite different in the dosages used. For example, Dr. Leonardi pointed out that briakinumab had issues with infections and malignancies.   Briakinumab has opportunistic infections; whereas, ustekinumab does not. Additionally, there are a large number of squamous cells carcinomas developed in patients treated with briakinumab. There is a change in squamous cell carcinoma to basal cell carcinoma ratio in briakinumab versus placebo.  This was not seen with ustekinumab.  Therefore, putting the trials using briakinumab and ustekinumab together in a meta-analysis is difficult.

Regarding other differences, looking at the long-term data and only patients who are tolerant of medication in the ustekinumab trials is unfair. Dr. Gordon would argue that if you look at data over time, the retention rate was over 80% over five years in the ustekinumab trials.  He pointed out that the high percentage rate of retention is rare in clinical trials and he doesn’t feel that eliminating a large number of patients is  an issue here.

When you look at 0.11 what does that mean?

Dr. Gordon feels that the P value being 0.11, as presented by Dr. Leonardi, is very significant. If the experiment were redone 100 times, one would expect to find a difference between the intervention and the placebo 89 times out of 100. That is quite significant.

However, we have a P value and a standard for statistical significance for a reason and that is because we need to be stringent about our conclusions and when they get too close together, it can be difficult to draw any final conclusions. It doesn’t say the magnitude of the problem, only that the two populations will be different.

With meta-analyses, there is another problem, and that is when trials are combined, you can have a trial that is the “driver”, i.e., one or two of the trials out of a larger group of trials will drive the results in one direction and everything else will be inconsistent with that; therefore, the validity of the meta-analysis can be called into question. In particular, when you combine drugs that are distinct and have a driver that is utilizing one of the medications, the validity can be questionable.

(Of note, Dr. Gordon is an author on the meta-analysis with Dr. Leonardi and feels that it is the best analysis that we can have)

A recent article in JAMA (August 2011) reported that there are two studies that are the drivers of all of the IL 12/23 data. The first of which is the briakinumab trial, the second of which is the ustekinumab Phase II trials in which the drug was given in a different fashion than it was given in Phase III. In fact, the numbers in the Phase III trials do not appear to have any statistical significance in the occurrence of MACE events. This makes it very difficult to draw conclusions on ustekinumab and MACE events. In fact, ustekinumab, at the doses given during the phase III, does not seem to statistically show effects at all—observationally, less so than anything else that has been seen.

Dr. Leonardi pointed out the initial increase in risk of MACE events with the initiation of treatment and then it levels off.  However, other data presented shows that there are events (randomly) throughout the course of treatment. Regarding the p40 subunit serum levels, there may not be enough information to draw conclusions based on this time course and the multiple events that are seen.

What does Dr. Gordon do for patients on ustekinumab?

Do you warn patients for potential cardiovascular risk?  Yes, patients should be aware of the potential risks.

Do you put patients on aspirin? In general, Dr. Gordon does not put people on aspirin; however, if the patient is at risk and should be on aspirin, then he recommends it. If a patient does not have risk factors, is under 40 and is hypertensive, he does not use aspirin.


This is a very difficult topic and many people have many differing opinions and feelings on it.  The answer regarding ustekinumab is not fully understood.  Regarding briakinumab, Dr. Gordon feels that there is a definite. Only with experience and time will clinicians have the answers regarding IL 12/23 and MACE events.








Psoriasis Update: 2012 Part 1

Craig Leonardi, MD

IL-12/23 Safety Issues

Cardiovascular Safety in Psoriatics Using Biologic Drugs.  Does a Signal Exist in the IL12/23 Pathway?

Case Report MACE in a Ustekinumab-Treated Psoriasis Patient

  • 47 year old construction worker
    • Caucasian male
    • Weight: 290 lbs
    • Negative Hx: DM, HTN, Tobacco
  • Psoriasis
    • 20 yr history
    • 15% BSA; PGA: M-S; DLQI: 12
    • No evidence of PsA
    • Past Tx: MTX, Etanercept, Infliximab, Golimumab
  • Current PsO Tx
    • Ustekinumab 45mg x 4 doses à 90mg x 2 doses
    • MTX 15mg SC QWk
    • Folic Acid 1mg QD
    • ASA 81mg QD (* This is something that Dr. Leonardi uses as add-on therapy)
  • Anterior wall MI
    • Normotensive
    • HgB A1C: 6.2
    • LDL-Chol: 108
    • Ejection Fraction: 45%
  • Two stents were placed

The Cardiologist commented: “Young for this type of event given his health status”

The question lies…what is it about this patient and his health status and the drug that he is currently taking, does it give him any protection about MACE events that can occur?

The answer is: no one knows right now and this is a hot debate that we all try to answer as best as we can…

Psoriasis patients have a wide and rich subset of many of the components of the Metabolic Syndrome such as diabetes mellitus, hyperlipidemia, coronary heart disease, and arterial hypertension that has been shown in much of the data.

We know from Dr. Joel Gelfand and colleagues, that our patients with psoriasis are at increased risk for myocardial infarction.

Methotrexate Reduces Incidence of Vascular Diseases in Psoriatics

  • Retrospective VAMC cohort study
    • 7615 patients with psoriasis
    • 6707 patients with rheumatoid arthritis
  • Covariates included age, sex, DM, HTN, dyslipidemia, and certain medications
  • MTX-treated pts had decreased vascular disease risk
    • Better: Low dose vs high dose
    • Best: Combination MTX and folic acid

From the Rheumatologists we have been following patients for many years….

So in treating RA patients with a TNF inhibitor, one could reduce cardiovascular events.

PsO: Risk of MI with anti-TNF therapy

This was a Kaiser Permanente psoriasis cohort of more than 24,000 patients. Patients had an ICD-9 of 696.1 (psoriasis) or 696.0 (PsA) for more than 3 prior visits and no MI prior to 2004 at the start of the study. The anti-TNF cohort was defined as receiving an anti-TNF for greater than 2 consecutive months. The oral/phototherapy cohort was anti-TNF-naïve, received oral/phototherapy for more than 2 consecutive months, and the “mild” cohort received no anti-TNF, oral therapy or phototherapy.  The researchers conducted a multivariate analysis using cardiac risk factors too look at a comparison between anti-TNF and other systemic therapy.

IL12 and 23 Blockade: A New Approach to Treating Psoriasis and Psoriatic Arthritis

There are new therapies currently available to Dermatologists, ustekinumab has been available for about 2 ¼ years; however, it is still a relatively new product. Both ustekinumab (IL-12) and briakinumab (IL-23) both block the p40 subunit.

When you block IL-12, you down-regulate a set a cytokines from a Th1 pathway, including INFy, IL-2 and TNF-alpha.  When you block IL-23, you down-regulate IL-17 alpha, IL-17f, IL-6, TNF-alpha, IL-21 and IL-22.

Function of Th17 Effector Cytokines


  • Expressed by memory NK and T cells
  • Increased in psoriatic skin
  • Subcutaneous injection à neutrophilia
  • Enhances inflammation
  • Enhances angiogenesis


  • Expressed in high levels by Th17 cells
  • Increased in psoriasis (skin and plasma)
  • Levels correspond to disease activity
  • Induces keratinocyte hyperproliferation (in vivo, in vitro)
  • Stimulates keratinocytes to secrete antimicrobial peptides


Both demonstrating positive effects…

Ustekinumab is a high-performing drug for psoriasis patients. One can see, by the data that at week 28, about 71-79% of patients are achieving a PASI 75; this is a huge achievement for these patients. Looking at briakinumab (ABT874), this product seemed to enable patients to achieve at PASI 75 within twelve weeks of treatment. Unfortunately, attached to this positive response was also a safety signal, specifically MACE events that is categorized as cardiac, stroke or death by cardiovascular reasons. There were five MACE events in treated arm and none in the placebo arm. There were also some other troubling issues such as six malignancies, all of which were squamous cell (2 were internal and 4 cutaneous), and again, none in the placebo group and there were five serious infections to one in the placebo arm.  There was an imbalance to MACE events, malignancies and infections as compared to placebo. This is problematic as with malignancies as to the fact that no one knows as to why the cancer issues showed up some early in this trial.  MACE events are very significant as it defies the conventional thought regarding systemic inflammation and cardiovascular disease—we expect that when inflammation is decreased, the cardiovascular status should improve; however, with that in mind, when looking back at the ustekinumab SAEs that occurred within the first twelve weeks, one can see an imbalance in the placebo versus the treated arms. One can see angina, stoke, congestive cardiomyopathy (and death), and CABG. Dr Leonardi points out that angina and coronary artery bypass are not necessarily MACE events, they would not actually qualify. All in all, between the phase II and phase III trials for ustekinumab there were five MACE events, an equal number to that of the briakinumab events.

What about infection rates?

When you’re looking at a subset of the drugs or patients who are doing well, you see positive results; however, that’s the not the case for the patients who are not doing well on drug.

Summary of MACE Events in Randomized Controlled PSO Trials (meta-analysis)

Dr Leonardi, along with a group of other concerned dermatologists, statisticians, cytokine biologists and cardiologists convened for a meeting. The goal of this meeting was to analyze the data from the published studies regarding the MACE events that occurred among these patients. The group was able to tabulate the data that exist among the IL-12/23 drugs and the TNF antagonists.

When looking at the data, one can see that there was one case of MACE reported in an adalimumab trial and there was another MACE event reported in an etanercept trial (one on treatment; one on placebo in the TNF antagonist trials). When looking at the IL-12/23 drugs, there are ten versus zero; that is a pretty compelling number.  Many argue that this is due to an unhealthy status of the patients; however, this is not seen with the placebo arm, so that question still remains.

What are the statistics?

*There was no statistical significance among the TNF trials

In both drugs, we see a flurry of activity and then it flattens out over time; therefore, the kinetics of both drugs seems to be similar.

We expect MACE events to DECREASE when systemic inflammatory diseases are treated. Why are we seeing a paradoxical increase in MACE events?

Dr Leonardi’s hypothesis tells us that when we look at serum p40 subunit levels following a single dose of ustekinumab, they peek at about 3-3 ½ weeks, and then they settle down over a 32-week period. Therefore, one can see an increase in drug concentration and in binding of the ligand, p40, during the initial period. The target for this drug is in the tissue (inflamed) skin; i.e., it is expected to pull p40, presumably in the form of IL-12 or IL-23, into the serum and perhaps it interacts with an atherosclerotic plaque. It could also be an increase in IL-12 or IL-23 delivery, indirectly, to atherosclerotic plaques. Literature also suggests that p40 subunits can also have a form of bioactivity if they dimerize. It is also possible that it is an expected biologic activity of the drug. It is unlikely; however, that it is due to patient selection bias, as it is not apparent in patients taking placebo.


IL 12/23 Antagonists: Possible Next Steps

  • Obtain complete datasets from Abbott, Centocor
  • Time-to-event details
  • Patient details (risk factors, basic demographics)
  • Pharmacokinetic profiles
  • All ischemic non-MACE events
  • Analysis of p40, IL12, IL23 serum levels during long term therapy
  • Routine and frequent safety updates (especially in relevant psoriasis populations)
  • Determine whether a pattern of comorbidities exists
  • FDA, EMA input based on review of both datasets

Ustekinumab: Recommendations for Use (Dr Leonardi’s Approach)

  • Consider all options when selecting a biologic tx
  • Know that psoriatics typically have multiple cardiac risk factors
  • Consider starting with low (45mg) dose regardless of pt weight
  • Consider adding ASA 81mg QD
  • Await further analysis (FDA, EMA, Abbott, Centocor)
  • Remember that all new drugs are ‘new’

 IL 12/23 Blockers and CV Risk? (Dr Leonardi’s Opinion)


  • Probable class effect demonstrated in 2 drugs
  • Equal number of MACE events in 1st 12 weeks (DBPC)
  • Increased rate of MACE in the early part of trials
  • Rate of MACE appears to decrease over time
  • Peak serum concentrations of drug correspond to MACE activity (ustekinumab)


  • Unanticipated finding
  • P= 0.11
    • Not significant at traditional levels (0.05)
    • Underpowered study for CV events
    • 11% probability that results (10 vs 0) is “by chance”






Inflammatory Disease in Little Kids

Lawrence F. Eichenfield, MD

In this presentation, Dr Eichenfield discusses inflammatory diseases in children in a clinically relevant manner.  Dr Eichenfield provides a review of the pathogenesis of atopic dermatitis (AD), the role of filaggrin, and allergies in AD.  He also updated us on new findings in pediatric psoriasis.

Atopic Dermatitis (AD)

When reviewing AD, it is important to consider the issues noted below:

  • Barrier dysfunction
  • Infection
  • Inflammation
  • Allergy
  • Itching

PEARL:  The phenotype, associated with ichtyhosis vulgaris, is associated with peanut allergy. Be careful when you take your atopic child or nephew to a baseball game or circus.

Filaggrin Insufficiency

Filaggrin haploinsufficiency is defined as a 50% reduction in the expression of the filaggrin protein, an important functional protein that influences epidermal function.   Filaggrin mutations are associated with decreased filaggrin production, as well as higher rates of development of associated conditions.  The odds ratios for the risk of peanut allergy, asthma, or atopic dermatitis with filaggrin mutations are greater as compared to individuals without filaggrin mutations. The odds ratios for atopic dermatitis and asthma, from meta-analyses involving several thousand patients display that FLG mutations confer an overall risk of asthma of 1.5, but this risk is restricted to patients with atopic dermatitis. The odds ratio for the complex phenotype of asthma plus atopic dermatitis is 3.3. The odds ratio for peanut allergy is 5.3 and is based on data from a single study.  Of interest is that there is no filaggrin in the mucosal surfaces of the mouth or esophagus so it likely that the peanut allergy is the result of epicutaneous sensitization. (Irvine AD, McLean I, Leung DYM. N Engl J Med 2011;365:1315-27)

The question is how does filaggrin deficiency affect the skin barrier?  The answer is that decrease in filaggrin expression increases skin permeability, increases skin pH, decreases natural moisturizing factor and decreases cell-to-cell cohesion impacting barrier function.

Of importance, even in individuals who do not have the filaggrin mutation, there is decreased filaggrin byproducts in actively, inflamed eczema.

Atopic dermatitis can be triggered by the chronic exposure of barrier-disrupted skin to percutaneous antigens due to abnormalities in filaggrin; however, only 30-50% have FLG mutations and most outgrow AD. 40% of patients with FLG-null alleles do not get AD. Therefore, there are other factors that influence AD development and course other than just filaggrin.

What are some of the traditional approaches and targeted therapies?

  • Moisturizing after bathing
  • Use of emollients
  • Targeted barrier repair products

These measures are part of maintenance care for all patients, and primary intervention for mild AD in infants

What are some of the things that can be done for the prevention of Atopic Dermatitis? In the past, physicians have considered:

  • Formula
  • Maternal diet
  • Infant diet
  • Allergen avoidance (both environmental and food)
  • Probiotics
  • Prebiotics

So far, none of strategies mentioned above have solid data for their efficacy.

Several international studies are currently looking at the role of early intervention in skin care in order to stop AD.

Anti-inflammatory therapy

There are typically two ways that a dermatologist handles a child with AD.

1. “As low as you can go (or just above where they were)”, i.e., the least strong topical steroid that can be used and 2: “Stronger steroids” to start, with tapering to less potent corticosteroids as the AD improves. Both of these approaches are reasonable. Many clinicians tend to “mix and match” the topical corticosteroids with the non-steroid topicals and utilize wet wraps with topical corticosteroids in patients with more difficult remissions.

Over the next few years, dermatologists will be seeing some new agents for the treatment of AD. These therapies include selective glucocoid agonist receptor stimulants, histamine 4 blockers and other molecules as well.

Wet Wrap Dressing with TCS Use: Effective, Rapid Control of Severe AD

Dawn Davis and colleagues conducted a study on wet wrap dressing in 218 patients who were hospitalized. The mean age of application was 6 years (2 months-17 years), the mean duration of hospital stay was 3.61 days (range 1-16) and all patients showed improvement.  45% of the patients showed 75-100% improvement; 38% of patients showed 50-75% improvement and 6% of patients showed a 25-50% improvement.

There are many methods to the use of wet wrap with topical corticosteroids and the benefits are clearly demonstrated.

Another important therapeutic intervention for AD, now recognized internationally, is education.   A struggle that clinicians face, is how to educate patients within the limited time of busy office settings, so that patients understand how to utilize their medicines, while also managing their fears with respect to the utilization of steroids and medications.

Pediatric Pearls and Conclusions

  • Prescribe specific amounts
  • Assess quantities of time
  • Discuss strengths and safety
  • Use Educational and Instructional materials
  • Handouts, Web-sites, Video training modules
  • Follow-up soon!  Studies show that there is more chance that they will follow their regimen and will have better clinical outcomes

Maintenance Therapy

  • Emollients alone? In 30-40% of infants, this may be sufficient
  • Intermittent corticosteroids
  • TCIs (delicate areas, persistent, frequently recurrent)
  • Targeted-Barrier-repair products
  • BRING THEM BACK when they’ll still be under control

What about the patients who are better, but not great or have persistent, frequent flaring?

  • Ask about feeding practices, atopic history
  • Establish aggressive maintenance plan
    • Intermittent CS and/or TCIs
    • Assess sleep and itching as endpoints
    • Trials of TBRP (targeted barrier repair products) and/or emollients
    • Consider anti-infectives, bleach baths/products
    • Check growth, infection history, differential diagnosis
    • Consider allergy referral

TCI Safety Information

There has been new information collected with regards to TCI safety, but the data have not yet been published. The FDA Pediatric Advisory Committee evaluated emerging data as part of a routine evaluation of TCI safety and use.   They looked at the epidemiology studies, the clinical studies, Data Safety Monitoring Boards and Post-marketing surveillance/Adverse Events Reporting System (AERS). The FDA found that there is no evidence of an association between TCIs and B-cell lymphomas but because of the limited data available, one cannot necessarily form conclusions from the published literature. The FDA also said that a literature review suggests a possible association between topical tacrolimus use and an increased risk of T-cell lymphoma.  The T-cell lymphoma association, however, may be due to use of the TCI in individuals reported as having eczema prior to the diagnosis of cutaneous T-cell lymphoma (known as protopathic effect).

It is important to remember that these are retrospective studies; so drawing conclusions can be difficult for the clinician.

An epidemiologic survey published by Tennis and Gelfand came to the same conclusions, i.e., there is little to no evidence of an increased risk of lymphomas overall or specific sub-types of lymphoma with topical TCI use and there is no evidence indicating that melanoma or non-melanoma skin cancer is associated with topical TCI use.


Dr Eichenfield poses the following question to the audience…

Staph aureus in patients with atopic dermatitis:

A.Is more likely to be MRSA than staph in infections in non-atopics less common than streptococcal infection

C.Is less likely to be MRSA than staph in infections in non-atopics

D.None of the above

MRSA and Atopic Dermatitis

Dermatologists should be aware that atopics have lower rates of MRSA infection than community-acquired staph infections. From an ecological perspective, the question is “does MSSA protect against MRSA?”

Translation into Clinical Practice

Bleach Baths and Alternatives*

  • ¼ to ½ cup for ½ to full tub of standard bleach (6%).
    • 5 cup for 40 gallon full tub is 0.005% concentration
    • Dilute Na hypochlorite and hypochlorous acid (Aurstat: marketed with HylatopicPlus)*
    • Na Hypochlorite body wash (CLn BodyWash)*

The AD market has responded to this and there are now at least two alternatives currently available to bleach baths. One of which is a tube of sodium hypochlorite and hypochlorous acid and it is paired with a ceramide-containing moisturizer. The other product is available over the internet that is a sodium hypochlorite body wash in a can.

Comorbidities and Atopic Dermatitis

Over the last few years the information available on attention deficit disorder has become much stronger as it relates to AD. Clinicians should know that behavioral disorders have been talked about in patients with AD for over 20 years. According to a recent publication in JAMA, as well as an unpublished large database survey study, ADD was seen more in younger children with AD and it was dose-dependent, in that, it correlated with the AD, the higher the severity, the more the risk of ADD. Depression was also higher in teens and adults. While there is no evidence to mandate screening, it should be considered.

Food Allergy and Eczema

About a17% of children with mild AD and 30-40% of moderate to severe children have at least one clinically relevant food allergy. However, food allergy testing (skin testing and IgE testing) can create a lot of false positives; in fact, 4 out of 5 tests may give a positive food allergy test yet there is no clinical relevance to the positive test.

(e.g. Milk: 238 of 1000 tested will have false +;  vs. 50 having clinically relevant allergy)

Consider Food allergy testing for moderate to severe, <5 yr old, with food reaction and/or disease resistant to standard topical regimens

Highlights from the Guidelines

The current guidelines suggest that children less than 5 years of age with moderate to severe AD be considered for FA evaluation for milk, egg, peanut, wheat, and soy, if at least one of the following conditions is met:

  • The child has persistent AD in spite of optimized management and topical therapy.
  • The child has a reliable history of an immediate reaction after ingestion of a specific food

Dr Eichenfield feels that it is appropriate to ask about food allergies and if a child has had a food allergy then an EPIPEN or EPIPEN Jr. should be prescribed.

Clinical Pearls for Atopic Dermatitis

  • Great skin care
  • Anti-inflammatory medication as needed, with most care as topical regimens
  • Maintenance care “as needed”
  • Keep regimens simple
  • Educate…in the office, on the net, wherever!
  • If really hard, seek help!

Pediatric Psoriasis

Obesity is a common comorbidity in pediatric patients with psoriasis. This is an important consideration for clinicians and counseling is important; however, this is being studied as to how this will correlate to adult risk. Regarding psoriatic arthritis in children, the most important screening test that dermatologists should remember to ask is about morning stiffness, i.e., arthritis. Pediatric psoriasis is typically treated with topical corticosteroids and Vitamin-D analogues; however, clinicians should not forget the appropriate placement of light therapy (NB-UVB is the most studied), which can be very effective. There are also combination products currently being studied such as Clobetasol/VitD. The National Psoriasis Foundation has a pediatric site that is kid-friendly and provides much needed information and resources.

Systemic treatment is still an ongoing battle with payors. There are no approved systemic treatments for children and adolescents with psoriasis.

In summary, there is a fair amount of new information for both AD and psoriasis and, in the future, hopefully more treatments will become available for pediatric patients.



New Drugs 2012 Part 2

Ted Rosen, MD & Neal Bhatia, MD

Imiquimod for Actinic Keratosis

There are three doses of imiquimod: 5%. 3.75% and the new 2.5% (which is approved, but not commercially available at this point).  What are their uses? Where does the 2.5% fit in? According to Dr Bhatia:

  • 5% for solid tumors or more aggressive fields?
  • 3.75% cycle therapies for routine or initial courses? It can also probably still be used for solid tumors
  • 2.5% for low-grade maintenance, weaning down from 6 week cycle, or routine for high-responders
  • Alternate among them?
  • Don’t expect any new trials or indications for awhile, so use your own experience



Icatibant is a SQ injected bradykinin B2 receptor antagonist, i.e., has a receptor affinity similar to bradykinin. Icatibant inhibits bradykinin, binding the B2 receptor; therefore, resulting in symptomatic relief and modulation of episodic flares of hereditary angioedema (HAE).

The injection is 10 mg per mL and comes as a 3 ml syringe, 25-gauge needle. Icatibant is indicated for the treatment of acute attacks of hereditary angioedema (HAE) in adults 18 years of age and older. Pediatric studies are currently underway. Icatibant is dosed at 30 mg injected subcutaneously in the abdomen. If the response is inadequate or symptoms recur, additional injections of 30 mg may be administered at intervals of at least 6 hours. It is important that healthcare providers and patients know not to administer more than 3 injections in 24 hours. Patients may self-administer upon recognition of an HAE attack.

The pivotal FAST-1 and FAST-2 trials studied icatibant and showed that it had a median time to 50% reduction from baseline symptoms ranging from 2.0 to 2.3 hours. Icatibant was approved in 2011 in the US.


The FDA approved Belimumab (BenlystaTM) for the treatment of autoantibody positive systemic lupus erythematosus (SLE) in March 2011. Belimumab is a human monoclonal antibody that is delivered via IV infusion and targets the soluble B lymphocyte stimulator (BLyS) protein.

BLyS was discovered by the Human Genome Sciences program in 1996 and plays a pivotal role in B-cell survival and B-cell proliferation by preventing normally occurring apoptosis.  During a normal immune response to infection, BLyS facilitates more B-cells to survive, proliferate and produce antibodies to fight infection. In many patients with SLE, higher concentrations of BLyS promote increased B-cell survival including the survival of autoreactive B-cells that in turn can mature into autoantibody-producing B-cells. Belimumab does not bind directly to B cells and does not directly deplete B-cell populations but instead binds BLyS.  In doing so belimumab inhibits the survival of autoreactive B-cells and reduces their differentiation into immunoglobulin-producing plasma cells. Belimumab has demonstrated proven efficacy in reducing SLE disease activity.


Azficel-T is indicated for the improvement of the appearance of moderate to severe nasolabial fold wrinkles in adults. It is an autologous cellular product; in that, it is made especially for patients from their own skin cells which are harvested via punch biopsy which is then shipped to a specialized lab for harvesting and growth of the patient’s fibroblasts. It is best used for acne scarring and nasolabial folds. It is important that dermatologists screen for any hypersensitivity and allergies. It is also important to recognize that this product is not meant for the “impatient” patient, as one cannot see instant results.

In reality, dermatologists should keep in mind that azficel-T is not inexpensive, i.e., $1000-$2000 to create a personalized bank of fibroblasts and each injection session costs between $700 and $1,000; therefore, the total cost may range from $3,100 to $5,000. There have been isolated cases of vasculitis, collagen vascular diseases, and keloids. There is lots of potential for good outcomes as well as mistakes with the use of azficel-T.