Introduction

The European Neuromuscular Centre has published new diagnostic criteria for inclusion body myositis. The new criteria reflect our increasing knowledge about IBM, the practical experience of IBM experts, and new diagnostic tools. The revised criteria will be important for IBM research studies and to determine which patients will qualify to enroll in future clinical trials. They will also be helpful for doctors who are diagnosing individual patients.

Since the term “inclusion body myositis” was first used in 1971, the definition of what exactly qualifies as Inclusion body myositis has been changing. This is natural, with the diagnosis evolving as doctors gain more knowledge about the disease.

The new guidelines for the diagnosis of inclusion body myositis will not have a significant effect on most people already diagnosed with IBM.

The new ENMC criteria are especially relevant for clinical trials and research studies. Clinical trials must have strict and uniform criteria for the diagnosis of IBM, to be sure that each spot in the trial is occupied by someone who truly does have IBM. These rigid criteria might exclude some patients who actually do have IBM, but that is sometimes unavoidable.

What is the European Neuromuscular Centre and How is it Involved with Inclusion Body Myositis?

The ENMC is an organization of top neuromuscular disease researchers and doctors from all over the world. Founded by European patient organizations, the ENMC sponsors frequent workshops, each bringing together a group of 20-30 experts focused on a specific topic.

A workshop devoted to IBM was held in 2011, and the participants agreed on new standards for diagnosing IBM. The results were published in 2013, and these guidelines have been referred to as the ENMC 2011 or ENMC 2013 criteria. These criteria have been used to determine eligibility for clinical trials, including the completed trial of arimoclomol and the current trials of sirolimus and Abcuro’s ABC008. They are also being used for the INSPIRE natural history study.

The new ENMC criteria were developed during another workshop on the topic of inclusion body myositis held in June, 2023. The results were published online last month.

What Were the Previous Diagnostic Criteria?

The first formal criteria for the diagnosis of IBM were the Griggs criteria, published in 1995. They relied primarily on muscle biopsy findings to diagnose IBM.

The ENMC 2011 criteria continued to use muscle biopsy findings, but increased the importance of patterns of muscle weakness. The diagnosis of IBM also required at least a 12-month history of progressive weakness, age of onset of at least 45 years, and a serum creatine kinase level of no more than 15 times the upper limit of normal. The criteria provided for three possible IBM diagnoses:

  • Clinical IBM: typical muscle weakness with some muscle biopsy findings
  • Clinico-pathological IBM: slightly atypical muscle weakness with all muscle biopsy findings
  • Probable IBM: slightly atypical muscle weakness with some muscle biopsy findings

Why Were New Criteria Needed?

With increasing knowledge and experience, it has become apparent that the previous criteria were overly strict, preventing some people who do have actual IBM from enrolling in clinical trials. Some people do not initially meet the older criteria for diagnosis, but as time passes and the disease progresses, they eventually do fulfill the criteria.

While it is important to be sure that people enrolled in a trial do have IBM, needlessly strict criteria are actually harmful. IBM is a rare disease, and it can be difficult to find enough patients for all research studies and trials. Strict criteria decrease the number of available patients. Also, it may turn out that medications will be most helpful in treating patients in the early stages of the disease, at a time when they may not yet meet traditional diagnostic criteria.

New Diagnostic Tools

The new criteria take advantage of new diagnostic techniques. Studies have shown that MRI and ultrasound images of muscles can help distinguish IBM from other conditions. During the past 10 years a new antibody test has been developed and studied—a positive result on an anti-cN1A (NT5C1A) antibody test supports the diagnosis of IBM. New techniques and ways of examining muscle biopsy specimens are also available.

How Do the New Criteria Differ from the 2011 EMNC Criteria?

One major change is the elimination of the three diagnostic categories, including the diagnosis of “probable” IBM. According to the new guidelines, either you have IBM or you don’t. This change will make things simpler and less confusing.

Text image stating the the diagnosis of "Probable" IBM will no longer be used

The new criteria recognize the wide variation among IBM patients. Age less than 45, unusually high serum creatine kinase levels, and a history of muscle weakness less than 12 months no longer automatically rule-out the diagnosis. Previous criteria gave importance to muscle weakness only in the muscles which straighten the knee and flex the fingers, but the new criteria acknowledge muscle weakness in other areas of the body. Some people with IBM first go to their doctor when their thigh muscles and fingers are still strong, but they have weakness elsewhere. For example, trouble swallowing, or dysphagia, is not even mentioned in the ENMC 2013 criteria. However, it is the third most common symptom, and sometimes the only symptom, when IBM patients are first diagnosed.

MRI, ultrasound, and anti-cN1A antibody testing can now support the diagnosis. Abnormalities in mitochondria are increasingly understood to be important, and they are now recognized as a supporting finding in the evaluation of muscle biopsies.

Making the Diagnosis is a Two-step Process

The first step is to determine the Clinical Presentation Type. This includes the patient’s age, history, symptoms, areas of muscle weakness, and creatine kinase levels.

The second step is to look at results of Confirmatory Investigations, including muscle biopsy, MRI, ultrasound, and anti-cN1A antibody testing.

Clinical Presentation Type —The First Step

The Clinical Presentation is characterized as either a Common Presentation or an Uncommon Presentation.

Common Presentation criteria are described in the Blue Box.

Text image describing the features of a Common Presentation of IBM

Uncommon Presentation criteria are described in the Green Box.

Text image describing Uncommon Presentation of IBM

Alternative Diagnoses must be strongly considered if the patient is described by any of the items listed in the Pink Box.

Text image listing reasons to consider an alternative diagnosis

Confirmatory Investigation Findings —The Second Step

Investigation findings are divided into two categories —a Mandatory Investigation Finding and Supportive Investigation Findings.

The Mandatory Investigation Finding is listed in the Orange Box.

Text image listing the mandatory investigation finding of endomysial inflammation

Supportive Investigation Findings are listed in the Yellow Box.

Text image listing the supportive investigation findings

How are These Criteria Used to Diagnose Inclusion Body Myositis?

Each person who has IBM will fit into either the Blue Box or the Green Box for Clinical Presentation. All people with IBM will have the features in the Orange Box. The findings in the Yellow Box are not always present, but some of these findings are necessary if the Clinical Presentation is not a Common Presentation with both finger flexor and knee extensor weakness.

There are three ways to establish a diagnosis of inclusion body myositis:

Text image listing one of the combinations of features which lead to the diagnosis of IBM

Text image listing one of the combinations of features which lead to the diagnosis of IBM

Text image listing one of the combinations of features which lead to the diagnosis of IBM

 

Importance of the Mandatory Investigation Finding

Notice that each of the three ways to make a diagnosis of IBM requires the Mandatory Investigation Finding (Orange Box). Inflammation consisting of lymphocytes in the endomysium surrounding non-necrotic muscle fibers must be present. If not, the diagnosis of IBM cannot be made using the new ENMC criteria.

Is Use of the New ENMC Criteria Always Required for the Diagnosis of IBM?

No. Remember, these criteria are primarily intended for use in research studies and clinical trials. While the criteria will be helpful to doctors as they see patients in their clinics, it is possible to diagnose IBM without following the ENMC criteria.

For example, the requirement for the Mandatory Investigation Finding means that a muscle biopsy is needed for the diagnosis of IBM using the ENMC criteria. This does not mean, however, that a doctor can never diagnose inclusion body myositis without a muscle biopsy. In some situations, a muscle biopsy may not be feasible. A knowledgeable doctor seeing an individual patient may make a diagnosis of IBM in this circumstance if the strength of the overall evidence is convincing, even though the patient will not be eligible for a clinical trial.

Summary

The new ENMC criteria for the diagnosis of inclusion body myositis reflect increasing knowledge, recognize the diversity of the disease in different patients, utilize new and improving technologies, and simplify the diagnosis.

For more information about the diagnosis of inclusion body myositis, visit the Diagnosis section of the Cure IBM website.

Kevin Dooley, MD

April 18, 2024

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