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June
2007: VOLUME
1, NUMBER 2
New
Developments in Biologic Therapy for Psoriasis
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eMedicalDermatololgy
Review is proud to present our first accredited PODCAST for 2007. Listen
here. |
This
audio interview with Mark Lebwohl, affiliated with The Mount Sinai School
of Medicine in New York, NY, discusses additional topics related to
Psoriasis.
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Welcome...
Johns
Hopkins University School of Medicine, The Institute for Johns Hopkins
Nursing and The University of Tennessee College of Pharmacy are pleased
to welcome you to the second issue of eMedicalDermatology Review.
Over the course of this series, we will be reporting on issues critical
to providing the safest and most effective care for patients with medical
dermatological conditions.
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after reading the newsletter, follow the instructions on the right side
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In
This Issue...
Five biologic therapies have already been introduced for the
treatment of psoriasis or psoriatic arthritis, and several others are
in development. While biologic therapy has rapidly gained acceptance
in the dermatology community, reports of side effects are increasing
as the use of these agents grows.
In this issue we review information
about a new biologic agent (anti IL-12/23) for psoriasis, present data
on the efficacy of TNF-α blockers for psoriasis, examine clinical
outcomes in patients switched from one TNF-α blocker to another,
and review the current literature on the side effects of TNF-α blockers. |
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Course
Directors
Bernard
A. Cohen, MD
Interim Chairman
of Dermatology,
Professor of Pediatrics
and Dermatology and Director of Pediatric Dermatology,
Johns Hopkins Children's
Center
Baltimore, MD
Susan
Matra Rabizadeh, MD, MBA
Department of Dermatology
Johns Hopkins Cosmetic
Center at Greenspring Station,
Baltimore, MD
Mark
Lebwohl, MD
Professor and Chairman
Department of Dermatology
The Mount Sinai School
of Medicine
New York, NY
Elizabeth
Sloand, PhD, CRNP
Assistant Professor
of Pediatric Nursing
Johns Hopkins University
School of Nursing
Baltimore, MD |
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GUEST
AUTHOR OF THE MONTH |
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Commentary
& Reviews:
Mark
Lebwohl, MD
Professor and Chairman,
Department of Dermatology
The Mount Sinai School
of Medicine
New York, NY |
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Guest
Faculty Disclosure
Mark
Lebwohl, MD, has disclosed that he has received grants
for clinical research and educational activities from, has served
as an advisor, consultant and speaker to, and has served as an investigator
for Abbott, Amgen, Astellas, Centocor, Genentech and Novartis.
Unlabeled/Unapproved Uses
The author has indicated
that there will be references to unlabeled/unapproved uses of drugs
or products in this presentation. Etanercept for hepatits C
is off-label; Etanercept, adalimumab and infliximab are off-label
for lupus. |
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The
Johns Hopkins University School of Medicine and The Institute for
Johns Hopkins Nursing take responsibility for the content, quality,
and the scientific integrity of this CE activity.
At the conclusion of this activity, participants should be
able to: |
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Discuss
new biologic therapies recently introduced or in development for
psoriasis |
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Describe
the current evidence concerning the side effects of specific biologic
agents |
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Detail
clinical outcomes occurring when switching patients from one biologic
agent to another |
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COMPLETE
THE POST TEST
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When
biologics first became available for psoriasis, they were met with
great excitement because they held the promise that we could treat
psoriasis effectively while avoiding the nephrotoxicity of cyclosporine,
and the bone marrow and hepatotoxicity of methotrexate. Dermatologists
quickly learned that the early biologics were not reliably effective
and were much too expensive, leading to skepticism about their use.
The skeptics did not dissuade
development, however, and we now have highly effective biologic therapies
for psoriasis. Five biologic agents are currently available for
the treatment of psoriasis or psoriatic arthritis, including: adalimumab,
alefacept, efalizumab, etanercept, and infliximab. The efficacy
of biologics is variable, but can be impressive: the Poulalhon
study found that even in patients who have failed three systemic therapies,
infliximab achieved 75% improvement in PASI scores in 68% of patients. Krueger’s
report on the early results of an extraordinarily effective novel biologic
agent, anti IL-12/23, which targets the p40 component of the latter
cytokines, shows that even a single subcutaneous injection of the lowest
dose tested achieved PASI 75 in 52% of patients. 81% of those
who received four weekly injections of the double dose achieved PASI
75.
Unfortunately, as we gain more
experience with biologics, we are likely to encounter more side effects,
some of which may or may not be related to these newly introduced drugs.
Bongartz et al published a widely quoted article suggesting that TNF
blockers increase the risk of serious infections and malignancy. Shortly
after publication of this article, numerous letters to the editor and
commentaries pointed out flaws in the study[1-3]. Specifically,
etanercept, a TNF blocker, was excluded from the study analyses, and
many of the malignancies reported were basal cell carcinomas and lymphomas.
If these are subtracted from the total, the risk of malignancy may not
be increased. It was also suggested that the risk of malignancy might
be related to the severity of rheumatoid arthritis rather than the drugs,
and the risk for disease progression was far greater than the risk of
serious side effects[1].
In a letter to the editor, representatives
of the FDA noted these discrepancies: they requested that the analyses
be adjusted for duration of exposure; requested meta-analyses for all
three TNF inhibitors; and compared the number of malignancies reported
to the number expected based on an established database — the Surveillance,
Epidemiology, End Results database (SEER). Compared to the SEER database,
they did not find an increase in malignancies for any of the TNF inhibitors[2].
Apart from potential risks of
malignancy and infection, a number of additional side effects have emerged,
as reported by Cohen at al. There have been numerous cases of psoriasis
or psoriasis-like skin lesions developing in patients with rheumatoid
arthritis or Crohn’s disease who do not have a personal or family history
of psoriasis. The temporal association with TNF-α inhibitor therapy
is not clear, but in those instances where psoriasis develops quickly
upon re-introduction of a second TNF-α inhibitor, the association
is difficult to dispute. Moreover, involvement of pubic skin and palms
and soles is commonly reported in this setting, not only in the patients
discussed here, but in other reports as well.
Finally, the association of TNF
inhibitor therapy and autoimmunity is confirmed by Poulalhon. 18 of
25 patients studied (72%) had antinuclear antibodies. Of the 18 patients,
17 had IgM anti-DSDNA-AB, but only four had IgG anti-DSDNA-AB, an increase
that was not statistically significant. Of interest, IgG anti-DSDNA-AB
poses more of a risk for the development of systemic lupus erythematosus
than IgM, which may explain why there are very few cases of infliximab-induced
lupus.
While real or potential side
effects must be considered when prescribing biologic therapies for psoriasis,
they must be weighed against the benefits of biologic therapies. In
patients with mild disease, there is little reason to consider any treatment
that might have significant side effects. However, in those with potentially
destructive joint disease or quality-of-life-destroying skin lesions,
the small risks are usually worth taking.
References
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ANTI
IL-12/23: A NEW TREATMENT FOR PSORIASIS |
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Krueger
GG, Langley RG, Leonardi C, Yeilding N, Guzzo C, Wang Y, Dooley
LT, Lebwohl M; CNTO 1275 Psoriasis Study Group. A human
interleukin-12/23 monoclonal antibody for the treatment of psoriasis. N
Engl J Med. 2007;356(6):580-92.
(For non-journal subscribers, an additional fee may apply
for full text articles.) |
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Human
interleukin-12 activates CD4+ T cells and natural killer cells, resulting
in release of interferon-γ and tumor necrosis factor-α.
Interleukin-23 activates T cells that express interleukin-17, which
in turn results in keratinocyte expression of inducible nitric oxide
synthase. The human monoclonal antibody studied in this trial targets
p40, a component of both IL-12 and IL-23.
Four doses were studied
in this double-blind placebo-controlled trial. Subjects were treated
with either a solitary injection of the low dose (45 mg) anti IL-12/23;
a double dose (90 mg); 4 weekly 45 mg doses (180 mg total); or 4
weekly 90 mg doses (360 mg total). Sixty-four patients were studied
in each group as well as in the placebo control group. At Week 16,
patients with a physicians’ global assessment less than excellent
received an additional injection of their original dose. At Week
20, the patients in the placebo group were treated with a single
90 mg injection. To enter into the study, patients had moderate-to-severe
psoriasis that made them candidates for phototherapy or systemic
therapy, and at least a 10% body surface area involvement. The average
body surface area affected in patients in this trial was 25%.
The investigators
report dramatic results. 52% of patients who received the single
low dose of anti IL-12/23 achieved PASI 75. In the 90 mg, 180 mg,
and 360 mg dose groups, 59%, 67%, and 81% achieved PASI 75 respectively,
showing a clear dose-dependent response. Only 37% of patients in
the treatment group did not achieve an excellent response, thus making
them eligible to receive an additional Week 16 dose. The proportion
of patients achieving PASI 50, PASI 75, and PASI 90 remained fairly
stable throughout Week 24 of the study.
Four percent of patients
in the active treatment groups discontinued the trial as a result
of adverse events, compared to 3% in the placebo group. Infections
occurred in 43% of patients undergoing active treatment, compared
to 39% of patients in the placebo group. Adverse events or infections
did not correlate with dose.
Serious adverse events
included hospitalizations for cellulitus and pneumonia in two patients
in the active treatment groups. Although two patients in the active
treatment groups also had myocardial infarctions, both had prior
risk factors for heart disease; one patient with hypertension and
hyperlipidemia had a stroke. There were also three malignancies in
the active treatment groups: one patient with a basal cell carcinoma,
one with a cutaneous squamous cell carcinoma, and one with prostate
cancer. In comparison, a solitary basal cell carcinoma as well as
a hospitalization for exacerbation of psoriasis occurred in the placebo
group. Blood chemistries and hematologies were similar between the
active and placebo groups.
In summary, this
anti IL-12/23 human monoclonal antibody was highly effective for
psoriasis, resulting in dose-dependent improvement and sustained
remissions. While this trial was too small to detect uncommon adverse
events, there were no signals suggesting a major risk for malignancy,
infection, or other serious adverse events. |
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INFLIXIMAB
EFFECTIVE FOR PSORIASIS THAT IS REFRACTORY TO NUMEROUS THERAPIES, BUT
ASSOCIATED WITH HIGH DEGREE OF AUTOANTIBODY FORMATION |
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Poulalhon
N, Begon E, Lebbé C, Lioté F, Lahfa M, Bengoufa D, Morel P, Dubertret
L, Bachelez H. A follow-up study in 28 patients treated
with infliximab for severe recalcitrant psoriasis: evidence for
efficacy and high incidence of biological autoimmunity. British
Journal of Dermatology. 2007;156:329-336.
(For non-journal subscribers, an additional fee may apply for
full text articles.) |
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Infliximab
is a TNF blocker that is highly effective for rheumatoid arthritis,
spondyloarthropathy, and Crohn’s disease, and has been proven to be
one of the most effective treatments available for psoriasis and psoriatic
arthritis. More than 60% of patients with rheumatoid arthritis treated
with infliximab develop antinuclear antibodies (ANA) as well as antidouble-stranded-DNA
antibodies (anti-DSDNA-AB) and anticardiolipin antibodies. ANA have
also been reported in Crohn’s disease patients treated with infliximab,
although the frequency is somewhat less than that reported in rheumatoid
arthritis. ANA are more commonly found in patients treated with infliximab
than those treated with etanercept.
There is limited data on the
development of autoantibodies in psoriasis patients treated with infliximab.
In an earlier study, approximately 25% of patients developed ANA 6 months
after starting a course of 3 infliximab infusions, but there was no
data on ANA titers or IgM or IgG isotypes of anti-DSDNA-AB. Moreover,
there have been no studies showing what happens to ANA following discontinuation
of the treatment.
Twenty patients with severe plaque
psoriasis, five with psoriatic erythroderma, and three with generalized
pustular psoriasis were recruited for the study. All had disease that
was refractory to 3 or more systemic treatments. As might be expected
considering the stringent entry criteria, psoriasis was generally severe
with a median PASI score of 28. Thirteen patients had psoriatic arthritis.
The patients were treated with infusions of infliximab (5 mg/kg) at
baseline, Week 2, Week 6, and every 8 weeks thereafter.
Therapeutic efficacy was dramatic
in this difficult-to-treat group of patients, with a median improvement
in PASI score of 88.1%. 88% achieved PASI 50, 68% PASI 75, and 52% PASI
90. Of the 5 patients with psoriatic erythroderma, PASI 75 was achieved
in 3 patients and PASI 90 in 2 patients. Of the 3 patients with generalized
pustular psoriasis, clearing occurred within 15 days of infliximab therapy
in 2 patients, with only residual keratoderma in 1 patient. Infliximab
was discontinued in the latter 3 patients because of a suspected infusion
reaction, a flare of plaque psoriasis, and loss of vascular access.
Two of the 3 patients experienced relapse of their pustular psoriasis
12 and 22 months after the last infusion, and one was still clear of
pustular lesions 9 months after therapy.
Three patients (12%) had ANA
at baseline and 18 (72%) had ANA at Week 22. 16 of the 18 patients had
a homogeneous ANA fluorescence pattern, 10 had a speckled pattern, and
4 a nucleolar pattern. At Week 22, 7 of the 25 patients with ANAs had
titers ≥1/1600; the median titer was 1/400 compared to baseline titers ≤1/80
among the 3 patients with ANAs before starting infliximab. 17 of the
18 patients with positive ANAs at Week 22 had IgM anti-DSDNA-AB compared
to 0 at baseline. Only 4 patients had IgG anti-DSDNA-AB at Week 22 compared
to 0 at baseline, a difference that was not statistically significant.
Of 8 patients checked for anti-ENA antibodies, none were positive either
at baseline or at Week 22. Only 4 patients were tested for anticardiolipin
antibodies: 1 was positive for anticardiolipin IgM at Week 22, and another
had anticardiolipin IgG at baseline and at Week 22. No patients had
clinical features of the antiphospholipid syndrome. Antihistone antibodies
were negative in 6 patients as well. Further, use of methotrexate did
not have any impact on the prevalence of any autoantibodies.
Of patients who discontinued
infliximab, 9 had ANA and anti-DSDNA-AB checked at their last infusions
and again between 5 and 21.7 months later. All 9 had positive ANA and
IgM anti-DSDNA-AB and one had IgG anti-DSDNA-AB. After discontinuation,
8 of 9 patients still had ANA at a median titer of 1/400 compared to
a median of 1/1600 at the time of discontinuation. Four of the patients
still had IgM anti-DSDNA-AB, and titers were reduced in three but slightly
increased in one patient. No patients met criteria for systemic lupus
erythematosus, although 3 patients developed symmetric peripheral polyarthralgias.
The 3 patients had ANA and IgM anti-DSDNA-AB at Week 22, and 1 had IgG
anti-DSDNA-AB. Measurement of antihistone autoantibodies was negative;
ESR, CBC, and urinary sediment were normal; and there were no other
features of lupus. One patient’s joint symptoms resolved despite continued
infliximab therapy. The authors suggested the possibility that the joint
pains might be related to a serum sickness-like infusion reaction. Psoriatic
arthritis was also considered.
In summary: infliximab is highly
effective, even in patients who have failed multiple systemic therapies
for psoriasis. It is also rapidly effective for generalized pustular
psoriasis and is effective for erythrodermic psoriasis. A high proportion
of patients develop autoantibodies, but very few go on to develop clinical
manifestations related to those autoantibodies.
References
| 1. |
Gottlieb
AB, Evans R, Li S, Dooley LT, Guzzo CA, Baker D, Bala M, Marano
CW, Menter A. Infliximab
induction therapy for patients with severe plaque-type psoriasis:
a randomized, double-blind, placebo-controlled trial. J Am Acad
Dermatol. 2004 Oct;51(4):534-42. |
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TNF
INHIBITORS: A REVIEW OF CLINICAL TRIALS FOR SERIOUS INFECTIONS AND
MALIGNANCIES |
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Bongartz
T, Sutton AJ, Sweeting MJ, Buchan I, Matteson EL, Montori V. Anti-TNF
Antibody Therapy in Rheumatoid Arthritis and the Risk of Serious
Infections and Malignancies: Systematic Review and Meta-analysis
of Rare Harmful Effects in Randomized Controlled Trials. JAMA.
2006;295(19);2275-2285.
(For non-journal subscribers, an additional fee may apply for
full text articles.) |
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There
is substantial in vitro and in vivo data to support a major role for
TNF in fighting infection and malignancy. While isolated trials of TNF
inhibitors have failed to demonstrate a statistically significant increase
in malignancies in treated patients compared to controls, there have
been numerous post-marketing reports of opportunistic infections and
of malignancies in patients treated with these agents. The authors of
this study therefore searched various databases for randomized placebo-controlled
trials lasting at least 12 weeks that studied the safety and efficacy
of adalimumab or infliximab for the treatment of rheumatoid arthritis.
Nine trials met their criteria for inclusion in this meta-analysis.
All data were analyzed to find serious infections that required antimicrobial
therapy or hospitalization or malignancies.
The authors point out that although
malignancies were rare in the single trials, they discovered 24 malignancies
in 3,493 (0.8%) patients who had received at least one dose of TNF inhibitors,
compared to only two malignancies in the 1,512 control patients (0.2%).
There was a dose-dependent increase in the risk of malignancies. The
pooled odds ratio for developing malignancy in patients treated with
TNF inhibitors was 3.3 compared to controls (95% confidence interval,
1.2-9.1).
126 patients treated with TNF
inhibitors developed serious infections compared to 26 patients in the
placebo groups, and the odds ratio for serious infection in rheumatoid
arthritis patients treated with TNF inhibitors was 2.0 compared to controls
(95% confidence interval, 1.3-3.1).
However, the authors point out
a number of possible flaws in their analysis. First, when the studied
events are rare, there is substantial mathematical instability, so that
small changes in the number of events can result in major changes in
the estimated relative risk. The authors also acknowledge that the different
trials included in their meta-analysis were heterogeneous in terms of
disease duration, disease activity, and other treatments used either
prior to the study or concomitantly with the TNF inhibitor.
Despite the finding of increased
risk of malignancy and infection, the authors point out the tremendous
value that TNF inhibitors confer on patients with rheumatoid arthritis.
Joint destruction is reduced, mobility increased, and quality of life
improved. They also point out that TNF inhibitors may lessen cardiovascular
events, which are the leading cause of death in patients with rheumatoid
arthritis. It is also of interest that this meta-analysis did not show
an increase in malignancies with longer study duration, and the authors
suggest that TNF inhibitors may accelerate pre-existing sub-clinical
malignancies rather than induce malignancies. In any case, the overall
risks of therapy with TNF inhibitors must be weighed against their benefits. |
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TNF-INDUCED
PSORIASIS: AN UNCOMMON AND UNEXPECTED SIDE EFFECT |
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Cohen
JD, Bournerias I, Buffard V, Paufler A, Chevalier X, Bagot M, Claudepierre
P. Psoriasis Induced by Tumor Necrosis Factor-α Antagonist
Therapy: A Case Series. Journal of Rheumatology. 2007;34(2):380-85.
(For non-journal subscribers, an additional fee may apply for
full text articles.) |
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TNF
blockers have been used in hundreds of thousands of patients for the
treatment of rheumatoid arthritis, Crohn’s disease, ankylosing spondylitis,
and other illnesses as well as psoriasis and psoriatic arthritis. Cutaneous
side effects include skin infections, eczematous reactions, drug eruptions,
vasculitis, cutaneous lupus, and possibly squamous cell carcinoma of
the skin. The authors report six cases of new onset psoriasis among
the 400 patients whom they treated with TNF blockers.
The six patients whom they reported
had rheumatoid arthritis (2), Crohn’s disease and spondyloarthropathy
(3), and ankylosing spondylitis (1). Five of the patients were treated
with infliximab, and in two of the patients, infliximab was discontinued
and the patients were treated with etanercept. A sixth patient was treated
only with etanercept and methotrexate. Concomitant medications included
methotrexate in two patients and azathioprine in one. The time course
to developing psoriasis after starting on the TNF blocker was quite
variable: one patient developed psoriasis after 41 months following
the initiation of infliximab infusions; another developed psoriasis-like
skin lesions 2 months after starting.
The distribution of skin lesions
was also quite varied. Pubic lesions developed in three patients, and
palmoplantar lesions in another three patients. One of the patients
with palmoplantar lesions developed pustules on the palms and soles.
Psoriasis resolved in all patients with either topical therapy, discontinuation
of the TNF blocker, or both. In four of the patients, the TNF blocker
was continued, but skin lesions responded to topical therapy.
In two of the most convincing
cases, psoriasis developed after infliximab and subsequently after etanercept.
In one of the cases, the patient developed skin lesions ten days after
her sixth infusion. The lesions persisted despite discontinuation of
infliximab, but cleared with topical corticosteroids. Several months
later, the patient’s spondyloarthropathy flared, necessitating treatment
with etanercept 25 mg twice per week. The patient developed psoriasiform
skin lesions 36 hours after the first injection. The lesions again responded
to treatment with topical corticosteroids.
In a second patient with Crohn’s disease and spondyloarthropathy, psoriasis
developed on the palms and soles and then three weeks after the third
infliximab infusion, skin lesions spread to the torso but cleared when
infliximab was discontinued. Several months later, the patient’s arthritis
flared, again necessitating treatment with etanercept 25 mg twice per
week. Palm and sole psoriasis recurred after the second injection. At
that time, the patient was noted to have pitted nails. Skin lesions
resolved following discontinuation of etanercept and administration
of topical therapy.
These six cases are typical of
TNF-α antagonist-induced psoriasis. The authors refer to at least
40 additional cases and quote an online survey in which the majority
of rheumatologists confirm that they have seen psoriasis or other skin
reactions during TNF-α therapy. Significant factors — the absence
of a personal or family history of psoriasis; the temporal association
of the development of skin lesions following treatment with TNF-α blockers,
especially in the two patients treated with different TNF-α blockers;
and skin biopsy in one patient — all support the diagnosis of TNF-α-induced
psoriasis. There have been reports of psoriasis following treatment
with infliximab, etanercept, and adalimumab. The authors point out that
psoriasis might have not been noticed by examining physicians before
TNF-α blockers were used, but the distribution of skin lesions,
in the pubic region and on the palms and soles, suggest that there are
some unique features of psoriasis in patients treated with TNF-α blockers.
Of note, there were no cases of erythrodermic psoriasis. The authors
also point out that psoriasis occurred despite concomitant methotrexate
and azathioprine in their patients. |
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SWITCHING:
WHEN ONE TNF BLOCKER FAILS, DO YOU SWITCH TO ANOTHER? RHEUMATOID ARTHRITIS
AS A MODEL |
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Hyrich
KL, Lunt M, Watson KD, Symmons DPM, Silman AJ, for the British Society
for Rheumatology Biologics Register. Outcomes After Switching
From One Anti-Tumor Necrosis Factor-α Agent to a Second Anti-Tumor
Necrosis Factor-α Agent in Patients With Rheumatoid Arthritis:
Results From a Large UK National Cohort Study. Arthritis & Rheumatism.
2007;56(1):13-20.
(For non-journal subscribers, an additional fee may apply for
full text articles.) |
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TNF-α inhibitors
had been used for the treatment of rheumatoid arthritis for years before
their introduction for the treatment of psoriasis. In contrast to the
data obtained in psoriasis trials, TNF blockers are similarly effective
to one another in treating rheumatoid arthritis. The three drugs vary
in a number of ways: infliximab is a chimeric monoclonal antibody; adalimumab
is a human monoclonal antibody; and etanercept is a fusion molecule
consisting of the FC portion of human IgG1 and the P75 TNF-α receptor.
Like the other two drugs, etanercept binds to TNF-α; however,
it also binds to lymphotoxin, which has a number of differing biologic
effects. The three drugs also have differing half-lives: etanercept
with the shortest at only 4 days, while adalimumab’s is 3 times longer.
The formation of antibodies against the drugs may play a role in their
biologic effects, and the chimeric nature of infliximab may lead to
more clinically significant antibody formation.
Significant numbers of patients
with rheumatoid arthritis and with psoriasis discontinue therapy with
particular TNF blockers, either because of inadequate efficacy or because
of the development of side effects. There are numerous reports of patients
failing therapy with one TNF blocker, only to succeed with a second
TNF blocker. The authors studied the likelihood of failure with a second
TNF blocker after either inadequate response or side effects from a
first TNF blocker in patients with rheumatoid arthritis.
The British Society for Rheumatology
Biologics Register requires that all rheumatoid arthritis patients starting
on TNF-α inhibitors register until 4,000 patients are recruited
for each of the TNF inhibitors on the market. In the current study,
only rheumatoid arthritis patients who had been followed for a minimum
of 6 months were included. 6,739 patients were analyzed for this study — 3,337
(45%) on infliximab, 2,826 (42%) on etanercept, and 876 (13%) on adalimumab
(reflecting the more recent approval of the latter drug). Patients were
followed for 6-61 months, with a mean follow-up period of 15 months.
More than 1/3 of patients discontinued
treatment with their first TNF inhibitor, with 12% stopping because
of lack of efficacy and 15% because of a side effect. Of those patients
who stopped, 46% switched to a second TNF inhibitor. More patients who
stopped their first agent because of inadequate efficacy (60%) started
a second TNF inhibitor compared to those stopping their first agent
because of side effects (35%).
At the time that data for this
study were analyzed, 73% of patients were still being treated with their
second TNF inhibitor, with a mean length of therapy of 6 months and
a maximum length of therapy of 32 months.
Sixteen percent of patients who
discontinued their first agent because of inadequate efficacy also discontinued
their second agent, whereas only 9% of patients who discontinued their
first TNF inhibitor because of side effects discontinued the second
agent for lack of efficacy.
For patients who discontinued
their first TNF inhibitor because of side effects, 20% discontinued
the second TNF inhibitor for side effects; whereas patients who discontinued
the first TNF inhibitor because of inadequate efficacy had a discontinuation
rate due to side effects of only 10% for the second TNF inhibitor.
Thus, inadequate efficacy with
one agent makes it more likely the second agent will fail for lack of
efficacy. Similarly, discontinuation for side effects with the first
agent makes it more likely the second agent will be discontinued for
side effects. Interestingly, of 71 patients who had side effects with both TNF
inhibitors, only 19 experienced the same side effect with both agents.
These data are important in that
they suggest that patients with rheumatoid arthritis failing one TNF
blocker may respond well to a different TNF blocker. In fact, the majority
of patients who switched to a second TNF blocker continued that therapy
beyond 6 months. Very often, patients who discontinue the second agent
do so for the same reasons that they discontinued the first. |
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activity has been planned and implemented in accordance with the
Essential Areas and Policies of the Accreditation Council for Continuing
Medical Education through the joint sponsorship of The Johns Hopkins
University School of Medicine, The Institute for Johns Hopkins Nursing,
and the University of Tennessee College of Pharmacy. The Johns Hopkins
University School of Medicine is accredited by the ACCME to provide
continuing medical education for physicians.
The Institute for
Johns Hopkins Nursing is accredited as a provider of continuing nursing
education by the American Nurses Credentialing Center’s Commission
on Accreditation. |
|
| Credit
Designations — back
to top |
|
Physicians
The Johns Hopkins
University School of Medicine designates this educational activity
for a maximum of 1.0 AMA PRA Category 1 Credit(s)TM.
Physicians should only claim credit commensurate with the extent
of their participation in the activity.
Nurses
This 1.0 contact
hour Educational Activity (Provider Directed/Learner Paced) is provided
by The Institute for Johns Hopkins Nursing. Each Newsletter carries
a maximum of 1 contact hour or a total of 12 contact hours for the
twelve newsletters in this program.
Pharmacists
 This
program is approved for one hour credit (0.1 CEUs) for the newsletter
and 0.5 hour credit (0.05 CEUs) for the podcast and is co-sponsored
by the University of Tennessee College of Pharmacy who is accredited
by the Accreditation Council for Pharmacy Education as a provider
of continuing pharmacy education. A statement of CE credit will be
mailed within 4 weeks of successful completion and evaluation of
the program. ACPE Program #064-999-07-251-H01.
Grievance Policy: A participant, sponsor, faculty
member or other individual wanting to file a grievance with respect
to any aspect of a program sponsored or co-sponsored by the UTCOP
may contact the Associate Dean for Continuing Education in writing.
The grievance will be reviewed and a response will be returned within
45 days of receiving the written statement. If not satisfied, an
appeal to the Dean of the College of Pharmacy can be made for a second
level of review. |
|
| Post-Test
— back
to top |
|
| To
take the post-test for eMedicalDermatology Review you will need
to visit The
Johns Hopkins University School of Medicine's CME website or The
Institute for Johns Hopkins Nursing or download a PDF of the
post-test from the issue itself for Pharmacy. If you have already
registered for another Hopkins CME program at these sites, simply
enter the requested information when prompted. Otherwise, complete
the registration form to begin the testing process. A passing grade
of 70% or higher on the post test/evaluation is required to receive
CME/CNE/CPE credit. |
|
| Statement
of Responsibility — back
to top |
|
| The
Johns Hopkins University School of Medicine and The Institute for
Johns Hopkins Nursing takes responsibility for the content, quality,
and scientific integrity of this CME/CNE/CPE activity. |
|
| Target
Audience — back
to top |
|
| This
activity has been developed for the Dermatologist, PharmD, Nurses,
Dermasurgeon, Dermatopathologist, Pediatric Dermatologist, Immunodermatologist,
Wound Care Specialist. |
|
| Learning
Objectives — | | | | |
