There is need for a brief but comprehensive objective assessment tool to help clinicians evaluate relapse symptoms in patients with multiple sclerosis (MS) and their impact on daily functioning, as well as response to treatment. The 2-part Assessing Relapse in Multiple Sclerosis (ARMS) questionnaire was developed to achieve these aims. Part 1 consists of 7 questions that evaluate relapse symptoms, impact on activities of daily living (ADL), overall functioning, and response to treatment for previous relapses. Part 2 consists of 7 questions that evaluate treatment response in terms of symptom relief, functioning, and tolerability. The ARMS questionnaire has been evaluated in 103 patients with MS. The most commonly reported relapse symptoms were numbness/tingling (67%), fatigue (58%), and leg/foot weakness (55%). Over half of patients reported that ADL or overall functioning were affected very much (47%) or severely (11%) by relapses. Prescribed treatments for relapses included intravenous and/or oral corticosteroids (87%) and adrenocorticotropic hormone (13%). Nearly half of patients reported that their symptoms were very much (33%) or completely resolved (16%) following treatment. The most commonly reported adverse events were sleep disturbance (45%), mood changes (33%), weight gain (29%), and increased appetite (26%). Systematic assessment of relapses and response to relapse treatment may help clinicians to optimize outcomes for MS patients.
Multiple sclerosis (MS), particularly relapsing remitting MS (RRMS), the most common form of the disease, is characterized by relapses [
Assessment tools, such as the Expanded Disability Status Scale (EDSS) [
The Assessing Relapse in Multiple Sclerosis (ARMS) questionnaire is a 2-part patient self-report assessment tool that was developed by a panel of expert MS nurses and is specifically designed for evaluating relapses and responses to relapse treatment [
This phase 4, pilot, cross-sectional descriptive/exploratory study was conducted at 5 clinical practice sites in the United States to assess the psychometric properties of the ARMS questionnaire in adult patients with MS experiencing a relapse (relapse was determined by the investigator; specific criteria were not defined by the study protocol).
The ARMS questionnaire (see Appendix 1 of the Supplementary Material available online at
The study included patients aged 18 years or older at the time of participation with a confirmed MS relapse, as determined by the investigator, and willingness to comply with all procedures and assessments. Patients or their designated representative provided informed written consent. Patients with pseudorelapse or any other condition that, in the opinion of the investigator, would not allow proper completion of the study were excluded.
Demographics and baseline characteristics were summarized using descriptive statistics. Responses to each item in Parts 1 and 2 of the ARMS questionnaire were summarized using descriptive statistics. Responses to items in Part 2 were summarized for the overall population and stratified by relapse treatment; post-hoc analyses evaluated differences between treatment groups.
A total composite score (TCS) was determined, using the three inter-related questions regarding response to relapse treatment. In Part 2, for example, questions 4 (symptom improvement), 5 (ADL), and 6 (return to previous state of health (RSH)) were evaluated. The TCS was calculated as the sum of the scores for these items. For this analysis, the score for the ADL item was calculated as 10 minus the value of the rating indicated by the patient, such that higher score values and greater positive changes from baseline indicate better functioning/improvement. Thus, for the TCS, the sum of the responses of the three questions has a range of 0 to 30, with higher scores indicating greater improvement/better functioning. The TCS was summarized descriptively. The distribution of the mean TCS was computed, and the 95% two-sided confidence interval for the mean TCS was computed based on Students
Two questions (Part 1, question 3 and Part 2, question 5) both specifically refer to ADL; the change in ADL was estimated based on these two questions; the score for each item was calculated as 10 minus the value of the rating indicated by the patient, such that higher score values and greater positive changes from baseline indicate better functioning/improvement. Two other questions (Part 1, question 6 and Part 2, question 6) both specifically refer to return to previous state of health (RSH); the change in RSH was estimated based on these two questions (using the value of the rating indicated by the patient), with higher scores indicating a more complete return to previous state of health. Changes in ADL and RSH scores were summarized descriptively. The distribution of the mean change in ADL and RSH scores was also computed. The 95% two-sided confidence interval for the mean change in ADL and RSH scores was computed based on Students
An additional composite score (partial composite score (PCS)) was computed based on the sum of the ADL and RSH questions. The PCS was computed separately for Part 1 (new relapse) and Part 2 (after relapse treatment) and summarized descriptively; again, the scores for the ADL items were calculated as 10 minus the rating provided by the patient, such that the sum of the item scores has a range of 0 to 20, with higher scores indicating better functioning/greater improvement. The distributions of the PCS mean composite scores were also computed, and the 95% two-sided confidence interval for the mean PCS was computed based on Students
The study included 103 patients. A summary of their demographic and clinical characteristics is provided in Table
Demographic and clinical characteristics of patients.
Patients completing Part 1 of ARMS questionnaire ( |
|
---|---|
Age, years, mean (SD) | 42.5 (11.2) |
Sex, |
|
Male | 14 (14) |
Female | 89 (86) |
Type of MS, |
( |
RRMS | 95 (98) |
SPMS | 2 (2) |
ARMS: Assessing Relapse in Multiple Sclerosis; SD: standard deviation; RRMS: relapsing remitting MS; SPMS: secondary progressive MS.
*Type of MS was not specified for 6 patients.
Characteristics of the current relapse are summarized in Table
Characteristics of current relapse.
Patients completing Part 1 of ARMS questionnaire ( |
|
---|---|
Time since symptoms began, |
|
≤3 days | 8 (8) |
4–7 days | 26 (25) |
8–15 days | 30 (29) |
≥16 days | 39 (38) |
Effect of symptoms on ADL, |
|
A little | 9 (9) |
Somewhat | 35 (34) |
Very much | 48 (47) |
Severely | 11 (11) |
Mean (SD) ADL score | 6.62 (2.1) |
ARMS: Assessing Relapse in Multiple Sclerosis; ADL: activities of daily living; SD: standard deviation.
New or worsening symptoms of current (new) relapse. ARMS: Assessing Relapse in Multiple Sclerosis.
Most patients (82%) were treated with intravenous (IV) and/or oral corticosteroids for their last relapse; and 72% of all patients indicated that they were very much improved or completely returned to their baseline state of health after treatment for their last relapse (Table
Outcome for last relapse.
Patients completing Part 1 of ARMS questionnaire ( |
|
---|---|
Time since last relapse, months | |
Mean (SD) | 13.4 (12.0) |
Range | 0–36 |
Treatment for last relapse, |
|
Corticosteroids (IV or oral) | 84 (82) |
ACTH | 5 (5) |
Other, no treatment, or not sure | 14 (14) |
Effect of treatment on RSH, |
( |
No improvement | 1 (1) |
A little | 8 (9) |
Somewhat | 17 (19) |
Very much | 41 (46) |
Returned to baseline | 23 (26) |
Mean (SD) RSH score | 7.22 (2.5) |
ACTH: adrenocorticotropic hormone; ADL: activities of daily living; ARMS: Assessing Relapse in Multiple Sclerosis; IV: intravenous; RSH: return to previous state of health; SD: standard deviation.
*Responses were not provided by 13 patients who reported no treatment or not sure of treatment for their last relapse.
Adverse events associated with last relapse treatment. ARMS: Assessing Relapse in Multiple Sclerosis.
All 103 patients who completed Part 1 of the ARMS also completed Part 2. The majority of follow-up assessments were conducted by phone (74%), and the majority of questionnaires were completed by office staff (79%).
The majority of patients were treated with corticosteroids for their current relapse (87%). Adrenocorticotropic hormone (ACTH) was the only other treatment reported (13%) (Table
ARMS Questionnaire Part 2—Treatment and outcomes for current relapse.
Patients completing Part 2 of ARMS Questionnaire ( |
||||
---|---|---|---|---|
Treatment for current relapse, |
||||
Any corticosteroids (IV or oral) | 90 (87) | |||
IV corticosteroids | 89 (86) | |||
Oral corticosteroids | 1 (1) | |||
Oral corticosteroids after IV | 23 (22) | |||
ACTH | 13 (13) | |||
| ||||
Total ( |
Corticosteroids ( |
ACTH ( |
|
|
| ||||
Completed prescribed treatment, |
100 (97) | 87 (97) | 13 (100) | |
Time since treatment completed, days | ||||
Mean (SD) | 28.2 (9.7) | 29.0 (9.8) | 22.2 (5.8) | |
Range | 8–90 | 8–90 | 14–30 | |
Treatment improved relapse symptoms, |
0.756 | |||
Got worse | 3 (3) | 3 (3) | 0 | |
No improvement | 6 (6) | 5 (6) | 1 (8) | |
A little | 12 (12) | 9 (10) | 3 (23) | |
Somewhat | 32 (31) | 28 (31) | 4 (31) | |
Very much | 34 (33) | 31 (34) | 3 (23) | |
Completely resolved | 16 (16) | 14 (16) | 2 (15) | |
Effect of symptoms on ADL after treatment, |
0.228 | |||
Not at all | 15 (15) | 13 (14) | 2 (15) | |
A little | 35 (34) | 34 (38) | 1 (8) | |
Somewhat | 37 (36) | 30 (33) | 7 (54) | |
Very much | 14 (14) | 11 (12) | 3 (23) | |
Severely | 2 (2) | 2 (2) | 0 | |
Effect of treatment on RSH, |
0.444 | |||
Got worse | 3 (3) | 3 (3) | 0 | |
No improvement | 7 (7) | 5 (6) | 2 (15) | |
A little | 13 (13) | 11 (12) | 2 (15) | |
Somewhat | 35 (34) | 29 (32) | 6 (46) | |
Very much | 27 (26) | 26 (29) | 1 (8) | |
Returned to baseline | 18 (17) | 16 (18) | 2 (15) |
ACTH: adrenocorticotropic hormone; ADL: activities of daily living; ARMS: Assessing Relapse in Multiple Sclerosis; IV: intravenous; RSH: return to previous state of health; SD: standard deviation.
The most common adverse events reported were sleep disturbance (overall incidence 45%), mood changes (33%), weight gain (29%), increased appetite (26%), increased fatigue (21%), headache (20%), and stomach upset (20%) (Figure
Adverse events with treatment for current relapse. ACTH: adrenocorticotropic hormone; ARMS: Assessing Relapse in Multiple Sclerosis.
Although the study was not designed or powered to evaluate differences between treatments, there were several notable differences between the corticosteroid and ACTH groups in the incidence of adverse events, including sleep disturbance (49% versus 15%), increased appetite (29% versus 8%), weight gain (32% versus 8%), and headache (23% versus 0%). Post-hoc analyses indicated a statistically significant difference between groups in sleep disturbance (
Mean scores for TCS, ADL, and RSH are summarized in Table
Total Composite Score, Activities of Daily Living Score, and Return to Previous State of Health Score.
Patients Completing Part 2 of ARMS Questionnaire |
|
|||
---|---|---|---|---|
Total ( |
Corticosteroids ( |
ACTH ( |
||
TCS after relapse, mean (SD) ( |
18.51 (7.6) | 18.92 (7.4) | 15.77 (8.8) | 0.166 |
ADL score, mean (SD) | ||||
Part 1—New relapse ( |
3.38 (2.1) | 3.43 (2.1) | 3.00 (1.9) | 0.483 |
Part 2—After relapse treatment ( |
6.21 (2.7) | 6.34 (2.7) | 5.31 (2.8) | 0.198 |
Change ( |
2.83 (2.8) | 2.91 (2.9) | 2.31 (2.4) | 0.478 |
RSH score, mean (SD) | ||||
Part 1—New relapse ( |
7.22 (2.5) | 7.33 (2.3) | 6.50 (3.3) | 0.283 |
Part 2—After relapse treatment ( |
6.00 (3.0) | 6.15 (3.0) | 5.00 (3.2) | 0.201 |
Change ( |
−1.11 (2.6) | −1.03 (2.7) | −1.67 (2.2) | 0.438 |
PCS, mean (SD) | ||||
Part 1—New relapse ( |
10.52 (3.6) | 10.69 (3.4) | 9.42 (4.6) | 0.251 |
Part 2—After relapse treatment ( |
12.38 (5.2) | 12.69 (5.0) | 10.31 (6.0) | 0.123 |
Change ( |
2.07 (4.4) | 2.29 (4.5) | 0.67 (3.4) | 0.233 |
ACTH: adrenocorticotropic hormone; ADL: activities of daily living; ARMS: Assessing Relapse in Multiple Sclerosis; PCS: partial composite score; RSH: return to previous state of health; SD: standard deviation; TCS: total composite score.
Analysis of the combined relationship of questions 4 (symptom improvement), 5 (ADL), and 6 (RSH) from Part 2 of the questionnaire with the TCS showed a high Cronbach
Correlations among total composite score and individual items (Total composite score calculated as the sum of scores from Questions 4, 5, and 6 from Part 2 of the ARMS questionnaire). ADL; activities of daily living; RSH: return to previous state of health; TCS: total composite score.
The ARMS questionnaire was developed by a working group of MS nurse experts from the United States and Canada, with the objective that it would be employed for the assessment of relapses and evaluation of response to relapse treatment. Results from this pilot study indicate that the ARMS questionnaire appears to be useful for evaluating relapses and response to acute relapse treatment. Cronbach’s
Results obtained with Part 1 of the ARMS questionnaire indicated substantial impact of relapses on patients with new appearance or increased severity of a large number of symptoms, including numbness/tingling, fatigue, leg/foot weakness, and difficulties in walking. Relapses also negatively affected ADL very much or severely in >50% of patients. This finding is consistent with prior results from a very large sample of MS patients which showed that those who experienced one or more relapses in the past 12 months had significantly greater functional disability than patients without relapses over this period [
Results from Parts 1 and 2 of the ARMS questionnaire indicated that corticosteroid treatment was associated with adverse events, including sleep disturbance, mood changes, and weight gain; all of these are well-known side effects of these agents [
The ARMS questionnaire may complement other instruments that have been employed to evaluate the status of patients with MS. The Expanded Disability Status Scale (EDSS) [
Some aspects of the study design may be considered limitations. For example, the study did not employ strict inclusion or exclusion criteria, and the diagnosis of relapse was at the discretion of the investigator. However, the ARMS questionnaire is intended to be used in a broad range of patients and the study was designed to evaluate the questionnaire’s ability to gauge the impact of relapses on patients and its ease of use to clinicians; as such, strict criteria to characterize relapses would limit the generalizability of the findings. In addition, we did not collect other clinical information that may be useful in evaluating differences in outcomes between patients (e.g., age at onset of disease, duration of disease, or use of disease modifying therapies). Finally, the study was not designed to compare outcomes with corticosteroids and ACTH, and the results should be considered with this in mind.
In summary, the results of this pilot study suggest that the ARMS questionnaire can be used in clinical practice settings to evaluate relapses and response to relapse treatments. The ARMS questionnaire may help clinicians to accurately and conveniently assess the nature and impact of relapses as well as the effectiveness of their current approaches to treatment. Furthermore, it may assist in promoting patient-clinician dialogue about relapses and their management across a variety of practice settings.
Data from this paper were presented at the 28th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS); 10–13 October 2012; Lyon, France.
Jennifer Smrtka is a consultant for CAN DO MS Organization, PRIME (CME Company), and Consensus Medical Corporation, has received honoraria for lectures on speakers bureaus for Acorda, Bayer, EMD Serono, Novartis, Pfizer, Genzyme, Questcor, and Teva, and has received payment for development of education presentations from PRIME. Alona Williamson has received honoraria or fees for participating on advisory boards for Bayer, Biogen, EMD Serono, Novartis, Questcor, and Teva Pharmaceuticals. Carol Saunders has been a consultant for Questcor Pharmaceuticals and received honoraria for speaking from Teva, Novartis, Bayer, and EMD Serono. Tracy Flemming Tracy has received honoraria for speaking from Teva and Biogen Idec and is on a speakers bureau for Biogen Idec. Constance Easterling has served as a consultant for PRIME, ACHL, Questcor, Allergan, EMD Serono, Pfizer, Biogen, and Teva Neuroscience, has received honoraria for speaking from Acorda, Bayer, Biogen, EMD Serono, Pfizer, Questcor, Genzyme, and Teva Neuroscience, and has received grant/research support from Bayer. Amy Perrin Ross has received a consulting fee or honorarium and support to travel to meetings from Questcor and is a consultant for Acorda, Allergan, Teva, Questcor, EMD Serono, and Genzyme. John Niewoehner and Nicole Mutschler are employees of Questcor.
The authors thank Sherri D. Jones, PharmD of MedVal Scientific Information Services, LLC, for providing medical writing and editorial assistance. This paper was prepared according to the International Society for Medical Publication Professionals’ “Good Publication Practice for Communicating Company-Sponsored Medical Research: The GPP2 Guidelines.” Funding to support this study and the preparation of this paper was provided by Questcor Pharmaceuticals.