Background

Early initiation of disease modifying therapy (DMT) in patients diagnosed with relapsing-remitting multiple sclerosis (RRMS) is recommended for optimal patient outcome. However, there may be multiple barriers to timely DMT initiation. A better understanding of patient-intrinsic factors may help physicians to guide patients during this critical phase of newly diagnosed chronic neurological disease.

Objectives

To determine rates of disease modifying therapy utilization and descriptive and demographic correlates of DMT use in individuals newly diagnosed with multiple sclerosis (MS).

Methods

A cohort of 230 individuals of two metropolitan MS centers was followed longitudinally assessing different psychological domains at 1, 2, 6, 9, and 12 months following their diagnosis of MS. The use of DMT throughout the first year following diagnosis of MS was assessed.

Results

Patients were 70.9% female and 88.2% white with a mean age of 39 years (range 18-71), mean baseline EDSS of 3.9 (range 0-7) and predominantly relapsing-remitting MS (204 RRMS, others were clinically isolated syndrome or not specified). Participants had 15.3 years of education (10-21) and 176 (76.5%) were working (others unemployed, retired, sick leave, disabled or student).

During their first year after MS diagnosis, 133 of 210 (63%) were not on a DMT at 1 month, 46 of 210 (22%) at 6 months and 47 of 201 (22%) patients were not on a disease modifying therapy at 12 months. Not being on a DMT at month 1 was not correlated with employment (r=0.019), years of education (r=-0.042), gender (-0.006), age (0.052) or EDSS (-0.043). Of those individuals who had initiated a DMT at 12 months, 52.4% individuals were treated with first-line injectable DMTs (glatiramer acetate or beta interferon), 35.7% with oral DMT and 11.9% with an infusion DMT (natalizumab or ocrelizumab).

Conclusions

In this prospective observational longitudinal study, initiation of DMT following diagnosis of MS was done in less than half of patients within the first month of the study (which was up to the first 4 months after diagnosis of MS). 22% of participants were not started on a DMT at 1 year. No definite demographic factors associated with time to DMT initiation could be identified in our cohort. Since early initiation of DMT has been associated with improved outcome, this phenomenon deserves further investigation. When treating patients with MS, special attention should be paid to facilitate an early start of DMT.

Background

Fatigue is a very common and disabling symptom of multiple sclerosis (MS) that is challenging to characterize appropriately for both research and clinical practice. The emergence of the NIH PROMIS item banks provides new possibilities for the development of outcome measures that are brief and optimally targeted. Substantial evidence has accumulated regarding the use of the PROMIS SF 1.0 – Fatigue (MS) 8b short form to discriminate levels of fatigue among individuals who have MS. The short form was developed with input from MS patients and clinicians.

Objectives

To establish minimal important difference (MID) estimates and interpretation tools for the PROMIS Fatigue (MS) 8b in MS populations.

Methods

Two observational studies were performed in MS populations, a cross-sectional study at two tertiary MS centers in the US (n=296) [US sample] and a longitudinal study in the UK MS Register cohort (n=384) [UK sample]. The analysis sample included patients with relapsing- or progressive MS, and those with Patient-Reported Web EDSS <7. Minimal important difference (MID) of PROMIS Fatigue (MS) 8b T-score was analyzed based on score changes over a 52-week follow-up using an anchor-based approach [UK sample]. An interpretative guide for PROMIS scores was also developed [US sample].

Results

At baseline, study participants had a mean age of 44.5 – 49.9 years, and mean PROMIS Fatigue (MS) 8b T-score of 57.4 – 59.9. Three anchors met criteria and were used in the MID analysis [ i.e. PROMIS GHS fatigue question, GHS PHC global question, and the Fatigue Severity Scale]. The standard error of measurement [SD * √ (1 – reliability)] of baseline T-scores was 2.8. A score change of 3.4 – 4.0 points is proposed as MID criteria for minimal improvement or worsening in fatigue. A heatmap facilitating interpretation of scores based on fatigue concerns on individual items was developed. For example, a T-score of 60 represents a fatigue level characterized by (often) getting tired easily, (sometimes) being too tired to think clearly, and (some-) interference with physical functioning, in the last 7 days.

Conclusions

This research extends the evidence underpinning the applicability of the PROMIS Fatigue (MS) 8b in routine clinical practice and clinical research. The score interpretation guide may aid the integration of PROMIS scores into clinical decision-making as well as facilitate clinician-patient communication. MID estimates will be useful in evaluating fatigue over time.

Background

There is need to respond to the challenges of developing a robust measurement technique for self-reporting of the level of physical functioning by patients with multiple sclerosis (MS) to help with identifying strategies for improving such outcome. The emergence of the NIH PROMIS item banks has opened new possibilities for developing instruments that are brief, optimally targeted and, potentially, have high precision. This holds promise for addressing unmet measurement needs in MS populations e.g. subtle physical disability changes.

Objectives

To describe the development, validity and applicability of a multiple sclerosis (MS)-specific PROMIS short form for use in relapsing and progressive MS types, the PROMIS SF v2.1 – Physical Function (MS) 15a.

Methods

A mixed-methods sequential design was followed in this research. Step (1) Concept elicitation (CE) interviews were carried out with MS patients (n=14). Step (2) results from the interviews were mapped to the PROMIS physical function item bank, to identify items relevant for MS patients. Subsequently, neurologists (n=6) rated the relevance of the item pool. Step (3) cognitive debriefing (CD) interviews were performed with MS patients to confirm the comprehensiveness, relevance and language clarity of the draft short form (n=48). Step (4) Further item reduction and psychometric evaluation was performed in two observational studies [cross-sectional study at two MS tertiary centers, n=296 (US); 96-week longitudinal study in UK MS Register cohort, n=558 (UK)].

Results

The initial item shortlist (48 items) from the NIH PROMIS item bank was revised in sequential steps, considering 1) optimization of coverage of the underlying concept, 2) results from CD interviews and 3) results from psychometric item-level analysis. Fifteen items were retained in the final short form.

Cronbach’s alpha (> 0.9) and ICC of test-retest scores (5 to 27 days) (> 0.9) indicated the short form’s strong reliability. Convergence validity was demonstrated by moderate-to-strong correlations with related PRO measures as well the EDSS (rho = ± 0.5 to 0.9). The short form discriminated between groups of patients according to levels of physical health and other criteria. A score banding system referencing responses on the individual items as anchors, was generated, to facilitate meaningful score interpretation.

Conclusions

The PROMIS PF (MS) 15a is a reliable and valid short form for assessing physical function with self-report in people living with MS. The inclusion of input from MS patients and neurologists during its qualitative phase of development, ensured comprehensiveness and relevance for both relapsing and progressive MS types.

Background

Fatigue is one of the most prevalent and impactful symptoms for people with multiple sclerosis (MS). MS fatigue can have detrimental effects on activities of daily living, employment, and quality of life. An inadequate number of studies have explored the extent to which fatigue and fatigue-related outcomes differ by MS disease course.

Objectives

To compare fatigue severity and fatigue interference, as well as identify common and unique demographic and clinical risk factors for fatigue severity and fatigue interference in persons with progressive MS compared to individuals with RRMS.

Methods

Participants were 573 community dwelling individuals with MS. The main outcome measures were fatigue severity and fatigue interference. T-test and chi-square analyses were used to compare group differences and multiple regression analyses were used to examine the extent to which the association of risk factors with fatigue severity and interference are moderated by MS subtype.

Results

There were no group differences between persons with progressive MS and RRMS in average fatigue severity or fatigue interference. Results also revealed there were no common risk factors between persons with progressive MS and RRMS. Longer MS disease duration was associated with lower average fatigue severity [b = -0.082, t(529) = -3.637, p < .001] for persons with progressive MS compared to persons with RRMS [b = -0.025, t(529) = -1.900, p = .058]. Having a college degree or higher was associated with higher fatigue interference in persons with progressive MS [b = 2.90, t(520) =2.28, p = .023] compared to persons with RRMS [b =-0.17, t(520) = -0.22, p = .825].

Conclusions

Contrary to previous research, in this sample, there were no group differences between persons with progressive MS and RRMS in average fatigue severity or fatigue interference. Given the similarity between fatigue and its correlates for both progressive and relapsing forms of MS, future research should consider if the interventions that work for fatigue management in people with relapsing forms of MS work similarly for people with progressive forms of MS.