Session Information
Date: Monday, November 6, 2017
Title: Systemic Sclerosis, Fibrosing Syndromes and Raynaud's – Clinical Aspects and Therapeutics Poster II
Session Type: ACR Poster Session B
Session Time: 9:00AM-11:00AM
Background/Purpose: A topical therapy for either prevention or palliation of attacks would offer unique advantages to selected patients with Raynaud phenomenon (RP). This study used 0.9% nitroglycerine (NTG) in a microemulsion formulation compared to vehicle to investigate clinical and physiologic responses to repetitive controlled cold challenge in individuals with RP secondary to connective tissue disease (CTD).
Methods: 65 subjects with CTD including 32 with systemic sclerosis (SSc), agreed to stop ongoing Rx for RP. Routinized assessments included 30 minutes of acclimatization at 22.2° C +/- 2.2 followed by up to 16 minutes in a cold room maintained at 4.4° C +/- 2.2 and 60 minutes of recovery. Finger temperature was monitored at regular intervals and subjects completed 10 cm VAS scales for numbness, tingling and pain as well as for overall RP attack severity. A Main Raynaud Symptom (MRS; most bothersome symptom of pain, numbness, or tingling) was chosen for each individual based on their highest VAS score during a baseline cold challenge. Active Rx or vehicle as placebo was applied in a blinded randomized sequence 30 minutes prior to each cold challenge with each treatment studied twice. An optional second application during cold exposure was permitted. An enriched subset of subjects responding to NTG but not to placebo was identified from the results of the first paired cold challenges for a subanalysis of responses in the final two cold challenges.
Results:
|
Topical NTG |
Vehicle |
P Value |
|
|
Main Raynaud Sx |
-20.77 mm |
-19.56 mm |
0.64 |
|
% Responders* |
33/64 51.6% |
32/64 50% |
0.93 |
|
MRS Enriched** |
-18.70 mm |
-13.76 mm |
0.45 |
|
AUC Skin Temp*** |
857.5 |
848.0 |
NS |
* Responders – subjects with > 15 mm improvement in MRS VAS
** Enriched Subset – Vascana response > 10 mm AND vehicle response < 15 mm on VAS during first paired cold challenge VAS
*** Area Under Curve – integral of skin temperature across time during cold exposure (degree-minutes)
Conclusion: Topical NTG was not superior to vehicle placebo in reducing symptoms of RP during controlled cold challenge. Although the VAS response in Main Raynaud Symptom was meaningful (-20.77 mm), response to placebo was of similar magnitude. This was also true of analysis of an enriched subset designed to exclude placebo responders. Skin temperature during cold challenge was chosen as an indirect measure of digital perfusion. The lack of difference in physiologic response mirrors the subjective measures. Placebo response remains a critical issue in RP trials. This is in spite of choice of a uniform population, personalization of definitions of response (self-selected MRS), a cold challenge designed to closely match in-life experiences and repetitive testing.
To cite this abstract in AMA style:
Khanna D, Mendez L, Namas R, Csuka ME, Caldron P, Molitor JA, Kivitz AJ, Waller P, Shapiro L, Najam S, Khan A, Steen VD, Chadha A, Seibold JR. Topical Nitroglycerine (NTG) Vs Matching Vehicle in Secondary Raynaud Phenomenon (RP) – a Double-Blind Crossover Study of Subjective and Physiologic Responses to Controlled Cold Challenge [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). https://acrabstracts.org/abstract/topical-nitroglycerine-ntg-vs-matching-vehicle-in-secondary-raynaud-phenomenon-rp-a-double-blind-crossover-study-of-subjective-and-physiologic-responses-to-controlled-cold-challenge/. Accessed .« Back to 2017 ACR/ARHP Annual Meeting
ACR Meeting Abstracts - https://acrabstracts.org/abstract/topical-nitroglycerine-ntg-vs-matching-vehicle-in-secondary-raynaud-phenomenon-rp-a-double-blind-crossover-study-of-subjective-and-physiologic-responses-to-controlled-cold-challenge/