Background/Purpose:

To assess changes in myositis core set measures, clinical and laboratory data, and paired muscle biopsies from NIH patients enrolled in the Rituximab in Myositis (RIM) trial.

Methods:

Eighteen patients (5 dermatomyositis [DM], 8 polymyositis [PM], 5 juvenile DM) completed muscle and skin assessments, patient-reported outcome measures (PROs), and laboratory tests following administration of rituximab. Adult patients had muscle biopsies at weeks 0 and 16.  Percent change and standardized response means (SRM) were examined over 44 weeks, and the percent change in the definitions of improvement (DOI) was compared.

Results:

Core set activity measures improved by 18 – 70% from weeks 0–44, although creatine kinase was the least sensitive to change (SRM 0.6 for CK vs. 1.2 – 2.0 for other core set measures).  Response rates at week 44 ranged from 72 – 94% by various DOIs for myositis. For DM patients, strength and functional measures improved by 17- 64%, and skin measures by 0 – 43% (Table).  Muscle strength measures (SRM 1.3 – 2.2) were more sensitive to change than skin assessments (SRM 0.6 – 1.1).  Constitutional, gastrointestinal, and pulmonary systems improved 44 – 70% (SRM 0.9 – 2.7). PROs, including SF-36 and PedsQL Fatigue scale, improved 25 – 28% (SRM 1.0 – 1.2), but the Fatigue Severity Scale and a dyspnea score did not change. 

CD20 B cells were generally depleted in the peripheral blood and frequently depleted in muscle.  No effects were observed on blood or muscle T cells or on other muscle biopsy parameters (inflammation, regeneration, vascular abnormalities, and fibrosis).  Seven of 10 patients with CD20 in the muscle at baseline depleted CD20 in the muscle and peripheral blood at week 16.  Of these, only one achieved the DOI at week 16, and 6 patients achieved the DOI at week 44.  One patient who responded clinically at weeks 16 and 44 depleted CD20 in the periphery and had reduced, but did not deplete, CD20 in the muscle.  Three patients had reduced or depleted CD20 in the periphery but increased CD20 in the muscle, and all 3 met the DOI at weeks 16 and 44.  In terms of memory B cells in the peripheral blood, 1 adult DM patient did not deplete CD20+CD27+ cells but met the DOI, and 2 juvenile DM patients depleted CD20+CD27+ cells but did not meet the DOI.  The other 11 patients with CD20+CD27+ cells depleted these cells and met improvement criteria. 

Conclusion:

Myositis patients enrolled at the NIH had similar high rates of clinical response to rituximab compared with patients in the overall RIM trial.  Most measures were very responsive, but muscle measures had a greater degree of change than skin.  Depletion of CD20+ cells in the periphery and target tissue did not always correlate with clinical response.

Measure [potential range]	Median Baseline value	Median % change  Week 0-44	Standardized Response Mean Week 0-44
Muscle
MMT-8 Score  [0-80]	54.5	28c	2.2
Total MMT Score  [0-260]	188.0	24c	2.1
QMT-8   [0-250 lb.]	61.8	64b	1.3
MDAAT Muscular VAS [0-10 cm]	4.8	48c	1.5
DAS Muscle     [0-11]	8.0	17a	1.4
CMAS   [0-52]	34.0	26a	1.2
HAQ/CHAQ  [0-3]	1.4	50a	1.2
Skin
CDASI       [0-168]	17.5	17	0.9
DLQI         [0-30]	4.5	43a	0.6
MDAAT Cutaneous VAS [0-10 cm]	3.4	28	1.1
DAS Skin     [0-9]	6.0	0	1.0
		a P < 0.05, b P < 0.01,   c P < 0.005

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/clinical-laboratory-and-cellular-responses-in-the-rituximab-in-myositis-trial-in-patients-enrolled-at-the-national-institutes-of-health/