ABSTRACT
Background: Fatigue, pain and faecal incontinence are common in people with IBD. However, little is known about co-existence of these multiple symptoms, how they inter-relate and whether people want help for these symptoms. In qualitative interviews, patients have reported that these symptoms are often ignored in clinical consultations where the focus is on inflammation, but that they are very bothered by these symptoms, even when disease is apparently in remission The aim of this study was to determine the presence and relationship between fatigue, pain and incontinence in people with inflammatory bowel disease, and desire for intervention for these symptoms Methods: A purpose-designed survey (online or postal), incorporating validated tools and demographic details, was sent to unselected UK clinic and UK IBD-BioResource adult patients. When the covid-19 pandemic halted clinic recruitment, additional self-selected UK recruits were solicited via social media. Using the validated PROMIS tools the following definitions were used for presence of symptoms: Fatigue: PROMIS fatigue T-score of 60 or more;pain: PROMIS pain intensity T-score of 60 or more;PROMIS bowel incontinence: Raw score of 50 or more. Participants also reported disease activity using the relevant PRO-2 score, IBD-Control, anxiety (GAD-7), depression (PHQ-9) and quality of life (EQ-5D-5L) which will all be reported elsewhere Results: A total of 8486 useable responses were received (7716 online 770 postal). 4176 reported Crohn's disease, 4255 had ulcerative colitis or other form of IBD. There were 3281 men and 4883 women. Median age was 51 years (range 18 - 92). 2550 (30%) reported fatigue 1766 (21%) pain and 4565 (54%) faecal incontinence according to the above definitions;925 (10.9%) reported having all three symptoms Demographics by symptom are shown in Table 1. Table 2 reports those participants indicating the presence of each symptom and each combination of symptoms. Table 3 shows a summary of self-defined severity and impact of symptoms (scoring scale 0-10 for both severity and impact of each symptom). Participants scored severity and impact a mean between 3.3 and 4.8, with a wide variation. 56% of all respondents (not just those with symptoms) "definitely" wanted help for fatigue;42% wanted help for pain;53% wanted help for incontinence. 29% reported "definitely" wanting help for all three symptoms (Table 4) Conclusion(s): This study confirms that fatigue, pain and urgency are common in IBD and for the first time reports the co-existence and unmet need for help with these symptoms.
ABSTRACT
Background: Whilst the introduction of disease modifying treatments (DMTs) has transformed the management of people with early/relapsing MS (pwRMS), the use of DMTs in people with MS who are largely or completely wheel chair-dependent (EDSS>6.5) remains controversial. Evidence suggests that slowing or stopping disease deterioration is possible even past this arbitrary (loss of ambulatory function) threshold. Pathology and anecdotal clinical data support the hypothesis that even at an advanced stage of MS (AMS) inflammatory activity is a key driver of functional decline and that effective immunotherapy may halt this process. Cladribine tablets are a highly effective and central nervous system (CNS) penetrant DMT for people with highly-active RMS. It effectively depletes B cells, particularly memory B cells, a likely key mechanism of disease control in MS. Evidence, suggesting that (i) a significantly higher number of CNS axons supply upper compared to lower limb functions and (ii) longer axons are more vulnerable to the effects of focal inflammatory demyelination than shorter ones, corroborate our hypothesis that upper limb function can be protected even beyond EDSS=6.5. Objectives: Primary Objective: To investigate whether cladribine tablets over 24 months is an effective DMT in people with AMS (pwAMS;EDSS=6.5-8.5) as measured using the 9-hole peg test (9HPT) peg speed. Secondary Objectives: To establish whether there is a difference in pwAMS between treatment with cladribine tablets or placebo in (i) blood/serum biomarkers of inflammation (lymphocyte subsets) and/or neurodegeneration (neurofilament light chain), (ii) MRI loss of brain volume and spinal cord cross sectional area, (iii) T2 lesion burden, (iv) hypointense lesions on T1 weighted scans, (v) quality of life, and (vi) whether cladribine is a cost-effective treatment for pwAMS. Methods: Randomised, double-blind, placebo-controlled phase IIb trial. To detect a 15% treatment effect in 9HPT peg speed with 90% power at 5% significance and 20% drop-out over 104 weeks n=200 pwAMS will be recruited across 20 UK MS centres. Results: Protocol and ancillary documents have been submitted for ethics approval. So far 17 centres have agreed to recruit pwAMS for ChariotMS. Due to the COVID-19 pandemic start of recruitment has been deferred to 04 Jan 2021. Conclusions: ChariotMS will be the first DMT-trial focussing on pwAMS. If successful, ChariotMS would expand the DMT landscape to include pwAMS and provide a platform for add-on therapies.