**Development and validation of classification criteria for idiopathic
inflammatory myopathies (IIM)**

**Abstract**

In patients with idiopathic inflammatory myopathies (IIM), there is a
clear need for improved treatment due to the persisting impaired muscle
function in most patients treated with the current regimens of high-dose
corticosteroids and immunosuppressive drugs. Recently the International
Myositis Assessment and Clinical Studies Group (IMACS), a multinational
and multidisciplinary group, developed consensus on outcome measures and
proposed definitions of improvement to be used in clinical trials for
adults and children. A significant and fundamental problem in clinical
studies, however, is the limitation of diagnostic criteria for
inflammatory myopathies (Bohan and Peter, 1975) as they are considered
too inclusive and may allow patients with some forms of muscle dystrophy
to be included in a group of inflammatory myopathies. These criteria
also misclassify patients with inclusion body myositis (IBM), and some
variables are not specified or operationally defined. Because evolving
concepts in pathogenesis have altered our thinking about myositis, and
since new diagnostic tools including MRI and myositis-specific
autoantibodies have been recently developed, it is now timely to develop
and validate new myositis classification criteria.

The aim of this project is to develop and validate classification
criteria for idiopathic inflammatory myopathies (IIM) and major
subgroups of the IIM in adults and children for clinical research,
especially clinical trials, and to document the reliability of these new
criteria.

Methods: A multidisciplinary and multinational collaborative project
including clinical scientists from neurology, rheumatology, paediatric
rheumatology, dermatology, pathology and epidemiology will be mounted.
We will establish a commitment from the major professional organizations
which represent the specialists who see patients with inflammatory
muscle disease, to review, vote, and if in agreement with the work, to
endorse the criteria. In addition, we will also seek support for the
project, including the support of representatives to the 2 meetings, the
analyses and the costs of the meetings. These include organizations in
the myositis field: EULAR, ACR, American Academy of Neurology (AAN), and
Academy of Dermatology. A steering committee (n= 8-10) will prepare
background materials, case forms consisting of candidate classification
criteria and the blinded analyses of data. A Working Committee (n=20-25)
and additional experts will collect data retrospectively from patients
with inflammatory myopathies and comparator groups. The performance
characteristics (sensitivity and specificity and predictive value) of
single criterion and combinations of criteria will be explored with
multivariate analyses, including logistic regression, CART, and Random
Forests Classification, to maximize discrimination between cases and
comparator conditions. The results will be summarized and presented at a
second working committee meeting. At this meeting the final criteria
will be determined after consensus has been reached. The next step will
be have them reviewed by sponsoring organizations and, if approved,
receive official endorsement. The International Myositis Assessment and
Clinical Studies Group (IMACS), European Neuromuscular Centre (ENMC),
the Muscle Study Group (MSG) and paediatric rheumatology networks
(PRINTO, CARRA and the PRES network for juvenile dermatomyositis) will
be invited as reviewers during the process. All sponsoring organizations
that ratify the criteria will have their names in the developed
international classification criteria of myositis.

Importance: Improved classification criteria for poly- and
dermatomyositis are important for clinical trials to test new drugs.
Improved classification criteria will also be very important in the work
to understand disease mechanisms and to develop new targeted therapies.

**1. Aims**

A combined effort to address both adult-onset and childhood-onset
myositis

Criteria should be developed for use by basic and clinical researchers
that distinguish the idiopathic inflammatory myopathies (IIM) from other
major mimicking conditions with high sensitivity and specificity; and

Criteria should be developed for use by basic and clinical researchers
that separate the major subgroups of the IIM from each other with high
sensitivity and specificity.

To test the reliability of these new criteria.

**2. Background**

Scientific advances in immunology and molecular biology over recent
years have led to increased knowledge of disease mechanisms and to the
development of new and more specific biologic therapies for patients
with chronic inflammatory diseases. In patients with chronic idiopathic
inflammatory myopathies, myositis, there is a clear need for improved
treatment due to the persisting impaired muscle function in most
patients treated with the current regimens of high-dose glucocorticoids
and immunosuppressive drugs such as methotrexate or azathioprine.
Currently recommended treatment is mainly based on uncontrolled studies
and case reports; few controlled trials have been conducted in patients
with myositis. A significant barrier to the conduct of studies has been
the lack of standardized validated outcome measures. The International
Myositis Assessment and Clinical Studies Group (IMACS), a multinational
and multidisciplinary group was established to standardize the conduct
and reporting of clinical studies in myositis. The IMACS has over 100
international members from adult rheumatology, neurology, pathology,
dermatology and paediatric rheumatology communities (see
https://dir-apps.niehs.nih.gov/imacs/). IMACS has developed consensus on
outcome measures and proposed definitions of improvement to be used in
clinical trials for adults and children with PM and DM (Miller et al
2001, Rider et al 2004).

Need and Relevance - Limitations of myositis classification criteria.

A significant and fundamental problem in clinical studies is the
classification criteria for inflammatory myopathies. Three different
criteria have been proposed (Bohan & Peter 1975, Tanimoto 1995,
Hoogendijk 2004) but the criteria of Bohan and Peter are the most often
used in clinical studies. Several limitations of these criteria are
recognised. Some criterion are not specified or operationally defined,
for example, the biopsy criterion is considered too inclusive and may
allow patients with some forms of muscle dystrophy to be included in a
group of inflammatory myopathies. These criteria also misclassify
patients with inclusion body myositis (IBM), which was not known when
these criteria were proposed, as having PM.

Since the 1980s, a variety of discoveries could impact the subsetting of
myositis. The biology of muscle in PM/DM has advanced with careful
immunohistochemical characterization (Engel & Arahata 1986) (Dalakas
1991). Magnetic resonance imaging (MRI), can now visualize muscle
inflammation and myositis-specific autoantibodies could be helpful for
diagnostic purposes but are not included in the Bohan and Peter criteria
(Love et al 1991).

Other criteria for inflammatory myopathies have been put forward. Engel
and Arahata proposed immuno-histopathology based criteria (Engel &
Arahata 1986). The Tanimoto criteria added arthritis, systemic
inflammatory signs, muscle pain and tenderness to the Bohan and Peter
criteria, to also distinguish myositis patients from other myopathies
and neuropathies (Tanimoto et al 1995). The American Academy of
Dermatology has published recommendations for diagnostic evaluation of
the skin manifestations in DM (Drake et al 1996). For IBM,
classification criteria have been developed and because this phenotype
is unresponsive to immunosuppressive treatment, patients with IBM should
be regarded as a separate entity in clinical trials (Griggs et al 1995).
The Bohan and Peter criteria have also been used for children with
myositis. A group of paediatric rheumatologists has started to revise
the criteria for this group (PreS network for juvenile dermatomyositis).

At the European Neuromuscular Centre (ENMC) workshop on trial design in
adult idiopathic inflammatory myopathies in 2003 (Hoogendijk et al 2004)
more extensive muscle biopsy findings were added to the criteria and two
new subsets of inflammatory myopathies were proposed:

a\) Non-specific myositis (in patients with non-specific
perimysial/perivascular infiltrates, but without biopsy features
diagnostic of PM or DM), and

b\) Immune-mediated necrotizing myopathy (characterized by absence of
inflammatory infiltrate) (Hoogendijk et al 2004).

The ENMC participants recommended revision of the current criteria to
exclude other diseases, to include information relevant to understanding
underlying pathogenesis and to facilitate the comparison of studies.

In summary, there is a consensus to revise the classification criteria
for PM and DM. Furthermore, most workers in the field believe that this
should be a collaborative effort between specialists in neurology,
rheumatology, paediatric rheumatology, dermatology, pathology and
epidemiology and that it should be international to ensure greatest
acceptance.

**Research Plan**

We think it important to involve scientists from a variety of fields
including adult and paediatric specialists in rheumatology, neurology,
dermatology, clinical epidemiology and statistics in the project. They
should also represent expertise from Europe and the U.S. A. A clinical
epidemiologist with experience in classification criteria, but who is
neutral in the myositis research field, will be the facilitator.

We will use methods and processes that have been successfully employed
in criteria development with planned inputs from a gradually increasing
circle of international stakeholders and experts to promote consensus
and "buy-in". A Steering Committee (n=8-10 internationally recognized
experts in the field), a Working Committee (n=20-25 additional experts)
and a larger number of invited reviewers (reference group) will be
involved.

A mandate and sponsorship from the American College of Rheumatology
(ACR), EULAR, American Academy of Neurology (AAN), the American Academy
of Dermatology, the Muscle Study Group (MSG), IMACS, the ENMC and the
paediatric networks CARRA, PRINTO and PreS network for juvenile
dermatomyositis will be secured.

The Steering Committee will prepare background materials and evidence -
tables for the Working Committee and analyse the blinded data. The
Steering Committee includes a representative of the ACR Subcommittee on
Classification and Response Criteria and one from the ECSICIT committee
(Standing Committee on International Clinical Studies Including Clinical
Trials) of EULAR.

The Working Committee will have the role of investigators of the study
and will collect clinical data. They will include diverse representation
with experts in the fields of rheumatology, neurology, paediatric
rheumatology and neurology, dermatology, neuropathology and
epidemiology. European and American experts and a representative from
the patient organisation, The Myositis Association (TMA) will be
invited.

The reviewers will be identified through the IMACS, ENMC, MSG networks
as well as from the paediatric networks: PreS network for juvenile
dermatomyositis, PRINTO and CARRA. These are large networks that can
easily recruit participants to collect clinical data and help
disseminate the proposed criteria. Since it is essential that revised
criteria be validated to distinguish myositis patients from subjects
with other connective tissue disorders and neuromuscular diseases that
may be mistaken for myositis, some of which are uncommon or rare,
multiple sites will need to identify comparator patients with these
disorders.

**3. Development of candidate criteria (Face and content validity)**

In 2004 a Steering Committee with eight experts from rheumatology,
neurology, paediatric rheumatology and epidemiology was formed and
formulated a process for development of the criteria. The experts
represent America and Europe and both genders.

\- The primary aim of the project is to develop classification criteria
for idiopathic inflammatory myopathies (IIM) and criteria that separate
the major subgroups of the IIM from each other with high sensitivity and
specificity.

This will be performed through a retrospective study. The focus is the
idiopathic inflammatory myopathies in adults and children. This includes
the myositis syndromes, including inclusion body myositis, polymyositis,
dermatomyositis, non-specific myositis, necrotizing myopathies, overlap
myositis and cancer-associated myositis as well as juvenile forms of
idiopathic inflammatory myopathies.

A list of variables to be included in the criteria will be defined. This
will be defined by experts in the field of muscle diseases and will be
decided after consensus has been reached at the first meeting of the
experts in the Steering and Working Committees.

The Steering committee has scrutinized previous criteria presented above
as well as inclusion criteria that have been used in published
controlled clinical trials of PM and DM. A complete set of potential
variables from all previous published and recently proposed criteria was
collected, adding up to a total of 188 variables. These variables
include: clinical signs and symptoms, such as the detailed pattern of
muscle weakness, pain, cutaneous and other organ manifestations; muscle
enzymes; EMG data; detailed muscle biopsy data; MRI information;
autoantibodies; initial clinical diagnosis; treatment and treatment
responses. Each Steering committee member was asked to identify the 10
most clinically sensible, important, easy to measure and reliable
variables for discriminating between the inflammatory myopathies and
other conditions which could be confused with myositis and that were
likely to be retrieved from patient records.

This smaller list of 50 variables will be further assessed for the
feasibility to retrieve information for these variables from 30 patient
records in a pilot study to be conducted by steering committee members.
Comments on the list of variables to collect will also be solicited from
experts in the IMACS, MSG, ENMC, CARRA, PRINTO networks and the PreS
network for juvenile dermatomyositis.

Variables will be defined and explained, by members of the Steering
Committee, in a glossary and have a short name, and a long name. Value
labels (male/female, yes/no, etc.) will be generated for all variables.

*Examples of domains and variables:* The Demographic domain will contain
date of birth, gender (0 if male, 1 if female), race (white, black,
Asian, etc.) among others. The History domain will contain date of
diagnosis, family history, concomitant diseases (Systemic sclerosis,
SLE, RA, etc). The Physical Findings domain will include the presence or
absence of weakness of specific muscle groups, skin rashes, etc. The
Laboratory domain will include serum levels of CK, LD, presence and
method of detection of autoantibodies (ANA, ENA, muscle specific
autoantibodies) muscle biopsy data, etc.

Variables which are not likely to be retrievable, imprecise in
measurement, or unreliable will be excluded, as well as variables which
are not likely to be obtained because they are difficult to measure, or
require technology which is not widely available or are not clinically
sensible to use. Some of the listed clinical variables have been tested
for inter-rater reliability in our previous studies through the IMACS
network ([Rider
LG](http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&term="Rider+LG"%5BAuthor%5D)
et al 2003). Skin variables (e.g. Gottron\'s papules and heliotrope
rash) have been tested by some of the members of this application and
data from those tests can be used in this project to assure reliability.
Muscle biopsies will be evaluated by a muscle -- biopsy committee,
please see below. The myositis specific autoantibodies will be tested in
one center with expertise in these autoantibody tests, on cases where
serum samples are available. Through the previous IMACS studies we have
gained great experience on how these types of clinical and laboratory
studies can be effectively performed in multi-center settings.

To develop consensus on the list of variables, the Delphi method will be
used before the first meeting of the Steering Committee and the Working
Committee. This will reduce the number of variables that will need to be
discussed at the meeting. At the first meeting the participants will
decide on the final variables. A modified nominal group technique will
be used to facilitate consensus.

The criteria will be imputed to discriminate redundant or overlapping
variables.

To avoid redundancy, we will examine Spearman correlations for
continuous variables and contingency tables for categorical variables
and drop those variables that are highly correlated/associated with each
other. For contingency tables -- as a first cut, we will use the
chi-square or the contingency coefficient which is a direct function of
chi-square.

**4. Validation**

*A. Variables*

The list of variables that has been developed and proposed by experts,
as described above under 3. "Development of candidate criteria (Face and
content validity)" will be tested in patients with inflammatory
myopathies as well as in other cases that could be confused with
myositis.

*B. Data collection*

Acquiring data: Data will be collected retrospectively by members of the
Steering Committee, Working Committee and from experts who are recruited
from the networks involved in the project. As there is no gold standard
for definition of myositis, each case will be defined according to the
expert submitting the case, who will list the variables that were used
for the diagnostic decision for each case. We will ask that only cases
with definitive diagnoses be submitted for this study. Cases will be
assembled to cover the entire spectrum of diseases under consideration
as well as the countries and referral patterns. Cases and control
conditions will have their clinical data recorded from patient records
on standardized case forms.

a\. Cases will include adult and juvenile cases and will attempt to
cover the spectrum of disease severity. This will be ensured by
involving clinicians from different disciplines; neurology,
rheumatology, dermatology and paediatric rheumatology. Cases from
secondary and tertiary referral centers will be included and from
different countries in Europe, the US, Canada, Latin America and
Australia.

b\. Comparator conditions which are commonly confused with idiopathic
inflammatory myopathies and cause a differential diagnostic problem will
be assembled. These conditions are:

-Non-inflammatory inclusion body myopathies

-Limb-girdle dystrophies

-Fascioscapulohumeral (FSH) dystrophy

-Drug/toxin associated myopathies (particularly associated with statin
use)

-Metabolic myopathies

-Mitochondrial myopathies

-Endocrine myopathies

-Rheumatic conditions; Systemic lupus erythematosus, Polymyalgia
Rheumatica, and Scleroderma

-Dermatologic conditions: discoid lupus erythematosus

Myositis cases and comparators that have the most complete data and are
also most secure in their diagnoses (from the referring expert) will be
candidates for inclusion in the study. There are two main groups, (1)
patients presenting with weakness as a primary complaint and (2)
patients presenting with rash or systemic features as a primary
complaint. For the first group we will mainly include patients with
muscle biopsies that include both myositis patients and comparator
conditions. For the second group, patients who have skin rash and most
of the other variables present will be included but a muscle biopsy may
not be required

The minimum number and types of allowable missing variables for cases
will be defined by the Working Committee at the first meeting. This will
limit the problem of missing data.

[]{.mark}

Each center will be asked to commit to submit data on 10 -- 15 patients
with definite diagnoses of DM, PM or IBM and at least 10 -- 15
additional cases that are not "myositis" but have a definite diagnosis
in the comparator list above. If the number of cases collected in the
first phase are inadequate in one or more diagnoses (see below), a
second phase of a directed collection of additional 10- 15 cases with
definite specific diagnoses will be made. If

enrollment goals are not achieved, participating sites could be
re-contacted to see if they can enroll additional patients with a
ceiling of 60 per site.

*Sample size calculations:*

We will request 200 patients per subgroup for a total of 1000 myositis
patients (4 major subgroups of PM, DM, IBM and Juvenile DM, and then
other miscellaneous subgroups) and then 1000 comparator patients (700
adults and 300 pediatric) without myositis. We assume that certain of
these patients or comparators will not be evaluable for certain
classification criteria (for example, ones that involve biopsies,
autoantibody testing, and certain imaging data) due to missing data.

Based upon the expected enrollment of 150 evaluable patients in each of
the 4 major subgroups of myositis (PM, DM, JDM and IBM), and the
expected enrollment of 500 evaluable comparators (300 adults and 200
pediatric), the following power calculations support this level of
enrollment:

Null Hypothesis: P1=P2 Alternative Hypothesis: P1\<\>P2. Continuity
Correction Used.

Allocation Odds

Power N1 N2 Ratio P1 P2 Ratio Alpha Beta

0.98279 600 500 0.833 0.75000 0.85000 1.889 0.05000 0.01721

0.97234 150 300 2.000 0.75000 0.90000 3.000 0.05000 0.02766

0.94547 150 200 1.333 0.75000 0.90000 3.000 0.05000 0.05453

Where N1 is a number of the total group or subgroup of myositis patients
and N2 is the sample size of the total or subgroup of comparator
patients and P1 and P2 are either sensitivity or specificity for the
myositis groups vs. the comparators. The Odds Ratio is
P2/(1-P2)/(P1/(1-P1)).  The beta is the type 2 error and is 1-power. 

*C. Data quality assurance and management.*

The data will be entered into a web-based survey (Survey Monkey) or by
manually into a paper questionnaire. Thereafter the data will be entered
into a standardized database at the site Karolinska Institutet in
Stockholm, Sweden, by a research assistant. We will create a template
for each data domain: demographic, physical exam, labs. There will
always be an anonymized linking case study number. The case study number
will be the link that is used to merge any data files, and must be
included in all domain files. The case study number will consist of a 3
digit center number followed by a 3 digit subject number.

Edit/Fix step: The web-based survey has some editing checks.
Furthermore, the recorded spreadsheets after being forwarded to the data
management center will be subject to some simple editing checks: data
will be assessed for within allowable range impossible values (e.g., age
\>150, etc). Any discrepancies need to be resolved by the center where
the data was acquired. Test step: This includes simple editing tests and
consistency checks. After merging data from datasheets, we will check to
see if they are consistent e.g. patient does not change sex etc.

*D. Muscle biopsy data*

A pathology committee of 3 members will be appointed by the Steering
Committee when the project has been funded. These 3 myopathologists will
read each available biopsy individually in a blinded fashion using a
standard scoring form. For quantitative variables (i.e., degree of
inflammation, etc.) the 3 readings will be averaged and for dichotomous
variables (i.e., presence of rimmed vacuoles within myocytes) only those
biopsies where 2 of the 3 pathologists agreed will be scored as
positive. The biopsy findings will be compared between the inflammatory
myopathies, comparator groups, and subsets of inflammatory myopathies.

An international muscle biopsy standardization study for juvenile
myositis cases was initiated in 2004 under the lead of Dr. Lucy
Wedderburn, London, UK, and she has agreed to advise us, using her
experience from this group, in the evaluation of muscle biopsies in this
study.

*E. Construct validity*

The new study criteria will be assessed in comparison with the Bohan and
Peter criteria for myositis, which are the most frequently used criteria
and will thus be the "gold standard" against which the new criteria will
be compared for sensitivity and specificity. New criteria will also be
tested against other published criteria of Tanimoto 1995 and Hoogendijk
2004. The ability of the new criterion to distinguish between
inflammatory myopathies from comparator groups will be tested as well as
the subgroups of myositis, polymyositis dermatomyositis, inclusion body
myositis and juvenile dermatomyositis. Sensitivity, specificity, and
predictive value of the potential new classification criteria schema
will compared to those of Bohan and Peter and other published criteria
(gold standards).

*F. Statistical analyses*

Dr Peter Lachenbruch, statisticiam Oregon, State University, will be
responsible for the statistical analyses of the study.

Analytical approaches will include descriptive statistics (means,
standard deviations, percentiles (10, 25, 50, 75, 90)) for the measured
variables and for derived variables. We will examine differences across
disease groups as a preliminary means of constructing various indices,
and to study differences in already defined indices -- e.g., number of
key symptoms present in each disease group. Many combinations of
variables can be generated to establish "criteria" but selecting some
combinations will be needed. An additional option is to use CART, which
will permit us to develop non-linear rules to classify subjects into IM
or other. Random Forest Classification analysis will also be used to
determine combinations of variables that best separate cases from other
diagnoses, and the relative importance of these variables in this
discrimination
(<http://www.stat.berkeley.edu/users/breiman/RandomForests/>).
Sensitivity and specificity will be computed for all criteria. The
Predictive value of a negative or a positive outcome depends on the
prevalence of the condition and the sensitivity and specificity. We will
compute these for a variety of prevalence values.

We can calculate candidates for diagnostic measures in many ways. Factor
analysis will be used to obtain a weighted combination of variables --
this could be simplified by omitting variables with low weights, and
rounding the weights to "nice" numbers. A second option would be to
determine weighted sums of variables that best separate the IM from the
other diseases. Techniques for this include logistic regression and
discriminant analysis. Random Forest Classification analysis would be a
very novel and practical approach. A third option is to solicit experts
for appropriate candidates for such measures. This can lead to many
options that depend on how much change is observed, what level of a
variable is needed, etc.

Final classification criteria

The final classification criteria will be validated using bootstrapping
methods to validate the top few criteria (or the top one). This could be
done with a large initial data set.

Manuscript will be prepared. Additional external expert opinion will be
sought. Revisions made accordingly with the consent and advice of the
entire committee and the report will be submitted to all stakeholder
organizations for review and hopefully formal endorsement. After this
voting the work will be submitted for publication.

*5. Project organization in detail*

Project director

1\. Ingrid E. Lundberg, professor in rheumatology, Rheumatology Unit,
Department of Medicine, Karolinska University Hospital, Solna,
Karolinska Institutet, Stockholm, Sweden

Steering Committee

\- Ingrid E. Lundberg, professor in rheumatology, Rheumatology Unit,
Department of Medicine, Karolinska University Hospital, Solna,
Karolinska Institutet, Stockholm, Sweden

\- Matthew Liang, MD, MPH, Rheumatologist, Epidemiologist, Harvard
Medical School, Brigham and Women´s Hospital, Facilitator of the
project.

\- Frederick W. Miller, M.D., Ph.D. Chief, Environmental Autoimmunity
Group, National Institute of Environmental Health Sciences, National
Institutes of Health, Bethesda, MD, U.S.A.

\- Anthony A. Amato, M.D., Department of Neurology, Brigham and Women's
Hospital, Harvard Medical School, Boston MA, U.S.A.

\- Lisa G. Rider, M.D. Deputy Chief, Environmental Autoimmunity Group,
NIEHS, National Institutes of Health, Bethesda, MD , U.S.A, (Pediatric
rheumatologist).

\- Clarissa Pilkington, Paediatric Rheumatologist, MBBS, Consultant in
Adolescent and Pediatric Rheumatology, Department of Rheumatology, Great
Ormond Street Hospital, London

\- Peter A. Lachenbruch, PhD, statistician, Oregon State University

\- Marianne de Visser, MD, Professor, Academic Medical Centre, Dept. of
Neurology, Amsterdam, The Netherlands

\- Richard J. Barohn, MD, Professor and Chairman, University of Kansas
Medical Center (KUMC), Department: Neurology, Kansas City, KS, USA

\- Victoria P Werth, M.D, Professor of Dermatology and Medicine,
University of Pennsylvania School of Medicine, Philadelphia, PA, USA

\- Gerald JD Hengstman, MD, PhD, Neuromuscular Centre Nijmegen,
Department of Neurology, Radboud University Nijmegen Medical Centre,
Nijmegen, The Netherlands

\- Richard Finkel, MD, Department of Neurology, Children's Hospital of
Philadelphia, University of Pennsylvania, Philadelphia, PA

An American College of Rheumatology Representative, Jas Singh, Minnesota
University

A Representative of EULAR will be invited to the next meeting

Working Committee

25-30 experts including rheumatologists, neurologists, dermatologist,
neuropathologist, from Europe and the US will be invited. A preliminary
list of experts is presented in Appendix 1.

Representative from the Myositis Association

A reference group

Reviewers will be invited from IMACS and other networks such as ENMC,
MSG and the paediatric networks; PRINTO, the PreS network for juvenile
dermatomyositis and CARRA.

*6. Dissemination of the recommendations*

Post the endorsed classification criteria on websites of ACR, EULAR and
other organizations.

Secure review by sponsoring organizations and if approved, official
endorsement.

All sponsoring organizations will have their names in the developed
classification criteria of myositis.

Abstracts to the EULAR, ACR and AAN scientific meetings.

Final manuscript publication

.

Implementation of the recommendations

This will be done through the already existing networks the IMACS, ENMC,
MSG, and PRINTO, PreS network for juvenile dermatomyositis and CARRA and
by using these criteria in clinical trials.

Relevance for ACR and EULAR

This will be a multidisciplinary project involving all of the key
players within this scientific field and the big collaborative study
groups, both for adults and juvenile myositis. It will also be a first
effort between the two major organisations ACR and EULAR to develop
classification criteria, and we are working to involve the major
neurology organisations as well to get wide acceptance for the criteria.

Timelines and milestones

During 2005 we defined a preliminary list of variables to be tested in a
pilot study during fall 2005. We achieved support from the ACR and
EULAR.

In November 2005 we had the first meeting with the Working Committee. A
list of variables for revised criteria was defined to be sent out to the
reference group for further comments.

In 2006 the list of variables was defined after comments from the
Reference group. A glossary was made.

In 2007 Institutional Review Board. Forms are being prepared and will be
sent out to participants. Clinical data will be collected.

2008\. Clinical data will be collected. Statistical analyses will be
performed. Revised criteria will be proposed. The proposed criteria will
be sent to reviewers in the reference groups.

2009: a second meeting with the Working Committee will be organized to
agree upon the criteria.

[]{.mark}

2009: Manuscript will be written. Seek ratification by EULAR, ACR, ENMC,
MSG and AAN. The name of the new criteria will be determined.

*References:*

\- Miller FW, Rider LG, Chung Y-L, Cooper R, Danko K, Farewell V,
Lundberg I, Morrison C, Oakley L, Oakley I, Pilkington C, Vencovsky J,
Vincent K, Scott DL, Isenberg DA, for the International Myositis Outcome
Assessment Collaborative Study Group. Proposed Preliminary Core Set
Measures for Disease Outcome Assessment In Adult and Juvenile Idiopathic
Inflammatory Myopathies. Rheumatol 11:1262-73, 2001

\- Rider LG, Giannini EH, Brunner HI, Ruperto N, James-Newton L, Reed
AM, Lachenbruch PA, Miller FW; International Myositis Assessment and
Clinical Studies Group\*. International consensus on preliminary
definitions of improvement in adult and juvenile myositis. Arthritis
Rheum; 50:2281-90, 2004

\- Bohan A, Peter JB: Polymyositis and dermatomyositis (second of two
parts). N Engl J Med 292:403-407, 1975

\- Bohan A, Peter JB: Polymyositis and dermatomyositis (first of two
parts). N Engl J Med 292:344-347, 1975

-Tanimoto K, Nakano K, Kano S, Mori S, Ueki H, Nishitani H, Sato T,
Kiuchi T, Ohashi Y. Classification criteria for polymyositis and
dermatomyositis. J Rheumatol.22:668-74, 1995

\- Hoogendijk JE, Amato AA, Lecky BR, Choy EH, Lundberg IE, Rose MR,
Vencovski J, de Visser M, Hughes RA.119th ENMC International
Workshop:Trial design in adult idiopathic inflammatory myopathies, with
the exception of inclusion body myositis 10-12 October 2003, Naarden,
The Netherlands. Neuromuscular Disorders, 14:337-45, 2004

\- Engel AG, Arahata K: Mononuclear cells in myopathies: Quantitation of
functionally distinct subsets, recognition of antigen-specific
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\-

Stockholm 2007-08-12

*Ingrid Lundberg*