Efficacy and tolerability of the antispasmodic, pridinol, in patients with muscle-pain – results of primepain, a retrospective analysis of open-label real-world data provided by the German pain E-registry

Figures & data

Figure 1. CONSORT diagram.

Table 1. Patient demographics.

Number of patients [n (%)]	1133	(100.0)
Gender female [n (%)]	617	(54.5)
Age [mean ± SD (median; range)]	53.9 ± 11.8	(54; 18–85)
BMI [mean ± SD (median; range)]	27.1 ± 4.7	(26.0; 16.7–59.6)
Pain duration: <1 week [n (%)]	691	(61.0)
1–2 weeks [n (%)]	172	(15.2)
3–4 weeks [n (%)]	168	(14.8)
5–12 weeks [n (%)]	64	(5.6)
longer [n (%)]	38	(3.4)
Stage of pain chronification … MPSS I [n (%)]	1020	(90.0)
…MPSS II [n (%)]	103	(9.1)
…MPSS III [n (%)]	10	(0.9)
Pain severity due to von Korff …stage 1 [n (%)]	878	(77.5)
…stage 2 [n (%)]	195	(17.2)
…stage 3 [n (%)]	51	(4.5)
…stage 4 [n (%)]	9	(0.8)
Current pharmacological pain treatments [mean ± SD (median; range)]	1.8 ± 0.9	(2; 1–5)
Patients … without any pain medication [n (%)]	0	(0.0)
… with 1 pain medication [n (%)]	546	(48.2)
with ≥2 pain medications [n (%)]	587	(51.8)
Pharmacological treatment with …nonopioidanalgesics [n (%)]	603	(53.2)
…NSAIDs [n (%)]	948	(83.7)
…mild opioids [n (%)]	108	(9.5)
…strong potent opioids [n (%)]	14	(1.2)
…antidepressants [n (%)]	55	(4.9)
…anticonvulsants [n (%)]	27	(2.4)
Current non-pharmacological pain treatments [mean ± SD (median; range)]	0.3 ± 0.9	(0; 0–6)
Patients … without any non-pharmacologic treatment [n (%)]	947	(83.6)
… with 1 non-pharmacologic treatment [n (%)]	93	(8.2)
with ≥2 non-pharmacologic treatments [n (%)]	93	(8.2)
Non-pharmacological treatment with …physiotherapy [n (%)]	129	(11.4)
…massage [n (%)]	48	(4.2)
…physical measures [n (%)]	44	(3.9)
…TENS [n (%)]	54	(4.8)
…acupuncture [n (%)]	39	(3.4)
…chiropractic measures [n (%)]	18	(1.6)
…psychotherapy [n (%)]	16	(1.4)
…cognitive behavioral treatment [n (%)]	6	(0.5)
…others [n (%)]	6	(0.5)
Concomittant diseases [mean ± SD (median; range)]	1.5 ± 1.1	(1; 0–5)
Patients … without any concomitant disease [n (%)]	192	(16.9)
… with 1 concomitant disease [n (%)]	451	(39.8)
with ≥2 concomitant diseases [n (%)]	490	(43.2)
Organ classes affected … cancer	0	(0.0)
nervous system	78	(6.9)
cardiovascular system	224	(19.8)
pulmonary system	133	(11.7)
gastrointestinal tract	129	(11.4)
liver, bile, pancreas	78	(6.9)
renal system	86	(7.6)
metabolic system	89	(7.9)
skin	136	(12.0)
musculoskeletal system	156	(13.8)
immune system	44	(3.9)
blood/coagulation	65	(5.7)
mental/psychiatric problems	84	(7.4)
allergies	233	(20.6)
others	167	(14.7)
none	192	(16.9)
Localization of muscle pain: (lower) back [n (%)]	490	(43.2)
hip/pelvis/leg [n (%)]	299	(26.4)
shoulder/neck [n (%)]	239	(21.1)
arm [n (%)]	23	(2.0)
without specification [n (%)]	46	(4.1)
muscle disease [n (%)]	36	(3.2)

Abbreviations. SD, standard deviation; BMI, body mass index; MPSS, Mainz pain staging system; NSAIDs, nonsteroidal anti-inflammatory drugs; TENS, transcutaneous electrical nerve stimulation.

Table 2. Baseline pain characteristics.

Number of patients [n (%)]	1133	(100.0)
Lowest 24-hr. pain intensity [LPI, mm VAS; mean ± SD (median, range)]	19.3 ± 19.0	(12; 0–78)
Medium 24-hr. pain intensity [API, mm VAS; mean ± SD (median, range)]	62.8 ± 12.0	(60; 28–100)
Highest 24-hr. pain intensity (HPI, mm VAS; mean ± SD (median, range)]	79.8 ± 15.9	(84; 52–100)
Average 24-hr. pain intensity index [PIX, mm VAS; mean ± SD (median, range)]	54.0 ± 10.2	(52; 27.0–86.7)
Patients without/with mild pain [PIX ≤30 mm VAS; n (%)]	10	(0.9)
Patients with moderate pain [PIX 31–50 mm VAS; n (%)]	412	(36.4)
Patients with strong pain [PIX 51–70 mm VAS; n (%)]	628	(55.4)
Patients with extreme pain [PIX >70 mm VAS; n (%)]	83	(7.3)
Pain-related disabilities of … home/family activities [mPDI1, mm VAS; mean ± SD (median, range)]	61.4 ± 20.5	(69; 0–100)
…recreation [mPDI2, mm VAS; mean ± SD (median, range)]	66.2 ± 21.9	(70; 0–100)
…social activities [mPDI3, mm VAS; mean ± SD (median, range)]	61.3 ± 25.8	(69; 0–100)
…occupation [mPDI4, mm VAS; mean ± SD (median, range)]	75.8 ± 21.6	(81; 0–100)
…self-care/personal maintenance [mPDI5, mm VAS; mean ± SD (median, range)]	37.6 ± 25.8	(31; 0–100)
…sleeps [mPDI6, mm VAS; mean ± SD (median, range)]	63.5 ± 23.0	(70; 0–100)
…overall quality-of-life [mPDI7, mm VAS; mean ± SD (median, range)]	63.4 ± 23.5	(70; 0–100)
Pain-related disabilities in daily life [mPDI, mm VAS; mean ± SD (median, range)]	61.3 ± 15.8	(63; 15.3–95.9)
Patients without/with mild disability [mPDI ≤30 mm VAS; [n (%)]	28	(2.5)
Patients with moderate disability [mPDI 31–50 mm VAS; n (%)]	258	(22.8)
Patients with strong disability [mPDI 51–70 mm VAS; n (%)]	491	(43.3)
Patients with severe disability [mPDI >70 mm VAS; n (%)]	356	(31.4)
Overall wellbeing [MQHHF, NRS5; mean ± SD (median, range)]	1.9 ± 1.0	(2; 0.0–4.9)
Patients with severe impairment [MQHHF <1.5; n (%)]	452	(39.9)
Patients with moderate impairment [MQHHF 1.6–3; n (%)]	559	(49.3)
Patients without/with mild impairment [MQHHF >3; n (%)]	122	(10.8)

Abbreviations. VAS, visual analogue scale; SD, standard deviation; MQHFF, Marburg questionnaire on habitual health findings.

Figure 2. Change from baseline to end of treatment for the average 24-h pain intensity (PIX). (a) The black lines represent baseline values for each individual patient, sorted by severity. Individual grey lines represent the change from baseline at end of treatment for each individual patient. The pre (baseline; BL) and end of treatment (EoT) boxplots show median (middle horizontal line in the box), and quartiles 25% and 75% (bottom and top lines of the box); whiskers correspond to the 5–95% quantiles; numbers given in boxplots are median (mean). (b, c) Show the absolute (mm VAS) and relative (percent) changes versus baseline for each individual, sorted by severity (i.e. identical to figure a) and boxplots show the corresponding median, 25–75%, and 5–95% quantiles as well as median (mean). Abbreviations. PIX, pain intensity index; VAS, visual analogue scale; CI, confidence interval; BL, baseline; EoT, end of treatment; ES, effect size; 95% CI: 95 percent confidence interval.

Figure 3. Change from baseline to end of treatment for pain-related disabilities in daily life (mPDI). (a) The black lines represent baseline values for each individual patient, sorted by severity. Individual grey lines represent the change from baseline at end of treatment for each individual patient. The pre (baseline; BL) and end of treatment (EoT) boxplots show median (middle horizontal line in the box), and quartiles 25% and 75% (bottom and top lines of the box); whiskers correspond to the 5–95% quantiles; numbers given in boxplots are median (mean). (b,c) Show the absolute (mm VAS) and relative (percent) changes versus baseline for each individual, sorted by severity (i.e. identical to figure a) and boxplots show the corresponding median, 25–75%, and 5–95% quantiles as well as median (mean). Abbreviations. mPDI, modified pain disability index; VAS, visual analogue scale; CI, confidence interval; BL, baseline; EoT, end of treatment; ES, effect size; 95% CI: 95 percent confidence interval.

Figure 4. Response (percent improvement between baseline and end of treatment) to pridinol. Notes: Left panel: cumulative proportion of patients with percent improvement for the average 24-h pain intensity (black) and the pain-related disabilities in daily life (grey). Right panel: categorial groups of patients with defined degrees of response to pridinol at end of treatment versus baseline.

Table 3. Response to treatment.

	Baseline	End of treatment
Average 24-h pain intensity (PIX, mm VAS; mean ± SD)	54.0 ± 10.2	20.9 ± 9.0
Absolute change versus baseline [mm VAS; mean ± SD (median)]	−33.1 ± 9.4 (−32.7)
Relative change versus baseline [percent; mean ± SD (median)]	−61.6 ± 14.5 (−61.9)
Patients with absolute improvement ≥ MCID vs. baseline [n (%)]	1069	(94.4)
Patients with relative improvement ≥50% vs. baseline [n (%)]	904	(79.8)
Patients with no/mild pain [PIX ≤30 mm VAS; n (%)]	10 (0.9%)	947 (83.6)
Significance	p<.001
Effect size (95% CI)	3.3	(3.0–3.7)
Pain-related disabilities in daily life (mPDI1–7, mm VAS; mean ± SD)	61.3 ± 15.8	26.5 ± 11.3
Absolute change vs. baseline [mm VAS; mean ± SD (median)]	−34.8 ± 13.8 (−34.7)
Relative change vs. baseline [percent; mean ± SD (median)]	−56.8 ± 17.2 (−54.7)
Patients with absolute improvement ≥ MCID vs. baseline [n (%)]	998	(88.1)
Patients with relative improvement ≥50% vs. baseline [n (%)]	757	(66.8)
Patients with no/mild disability [mPDI ≤30 mm VAS; n (%)]	28 (2.5%)	681 (60.1)
Significance	p < .001
Effect size (95% CI)	2.3	(2.1–2.7)
Overall wellbeing [MQHHF, NRS5; mean ± SD)	1.9 ± 1.0	2.5 ± 1.0
Absolute change vs. baseline [NRS5; mean ± SD (median)]	0.6 ± 1.0 (0.4)
Relative change vs. baseline [percent; mean ± SD (median)]	31.6 ± 88.3 (13.8)
Patients … with any worsening vs. baseline [n (%)]	151	(13.3)
… without change vs. baseline [n (%)]	165	(14.6)
…with an improvement vs. baseline [n (%)]	817	(72.1)
Patients without/with mild impairment [MQHHF >3; n (%)]	122 (10.8)	326 (28.8)
Significance	p < .001
Effect size (95% CI)	0.6	(0.5 − 0.7)

Abbreviations. PIX, pain intensity index; VAS, visual analogue scale; SD, standard deviation; MCID, minimal clinical important difference; mPDI, modified pain disability index; NRS, numerical rating scale; MQHFF, Marburg questionnaire on habitual health findings. ES, effect size; 95% CI, 95 percent confidence interval.

Figure 5. Scatterplot of the improvements for the average 24-h pain intensity index (PIX; x-axis) and the pain-related disabilities in daily life (mPDI; y-axis) at the end of treatment [each given as absolute (mm VAS) improvement versus baseline]. Notes: Dotted diagonal shows the linear correlation trend (incl. the coefficient of determination R2). Abbreviations. PIX, pain intensity index; mPDI, modified pain disability index; VAS, visual analogue scale.

Table 4. Changes in analgesic medication.

	Baseline	End of treatment	Δ (EoT→BL)	Signif.
Number of analgesics [mean ± SD (median)]	1.8 ± 0.9 (2)	1.1 ± 1.1 (1)	−0.6 ± 0.9 (0)	p < .001
Analgesic treatment with …nonopioidanalgesics [n (%)]	603 (53.2)	379 (33.5)	−224 (−37.1)	p < .001
…NSAIDs [n (%)]	948 (83.7)	622 (54.9)	−326 (−34.4)	p < .001
…mild opioids [n (%)]	108 (9.5)	82 (7.2)	−26 − 24.1)	p = .049
…strong potent opioids [n (%)]	14 (1.2)	14 (1.2)	0 (0.0)	p = ns
…antidepressants [n (%)]	55 (4.9)	43 (3.8)	−12 (−21.8)	p = ns
…anticonvulsants [n (%)]	27 (2.4)	22 (2.9)	−5 (−18.5)	p = ns
…none [n (%)]	0 (0.0)	349 (30.8)	349 (na)	p < .001
Patients … without pain medication change after pridinol [n (%)]	540 (47.7)
…with termination of ≥1 pain medication with pridinol [n (%)]	593 (52.3)
…with termination of any pain medication beyond pridinol [n (%)]	349 (30.8)
Demand of analgesics: none [n (%)]	0 (0)	349 (30.8)	349 (na)	p < .001
1–2 [n (%)]	911 (80.4)	652 (57.5)	–259 (–28.4)
≥3 [n (%)]	222 (19.6)	132 (11.7)	–90 (–40.5)

Abbreviations. Δ, difference; EoT, end of treatment; Signif., significance; SD, standard deviation; NSAIDs, non-steroidal anti-inflammatory drugs.

Table 5. Drug-related adverse events.

	(n)	(%/a%)
Total population	1145	(100/100)
Number of DRAEs reported	70
Patients with DRAEs	70	(6.2/6.2)
DRAE-related treatment discontinuations (pats.)	9	(0.8/12.9)
	DRAEs		Discontinuations
	(n)	(%/a%)	(n)	(%/a%)
all	70	(6.2/100.0)	9	(0.8/100.0)
headaches	16	(1.4/22.9)	1	(0.1/11.1)
dizziness	8	(0.7/11.4)	3	(0.3/33.3)
nausea	8	(0.7/11.4)	–	–
abdominal pain	8	(0.7/11.4)	–	–
somnolence	8	(0.7/11.4)	–	–
peripheral circulatory response	6	(0.5/8.6)	2	(0.2/22.2)
hypotension	5	(0.4/7.1)	1	(0.1/11.1)
tachycardia	3	(0.3/4.3)	1	(0.1/11.1)
dry mouth	3	(0.3/4.3)	–	–
weakness/asthenia	3	(0.3/4.3)	1	(0.1/11.1)
restlessness	2	(0.2/2.9)	–	–

Abbreviations. a%, adjusted percent; DRAEs, drug-related adverse events; pats., patients.

Figure 6. Summary of efficacy and tolerability information relevant for the primary endpoint calculation. DRAE: drug-related adverse event.