Table 2.
Clinical studies on hpCS in Hip, Knee and Hand OA, on formulation 1200 mg/die and on pharmacoeconomic impact
| Condition/topic First author [Ref.] Design |
Patients | Treatment/dose Control/dose Follow-up |
Summary of results, primary efficacy parameters |
|---|---|---|---|
| Hip OA | |||
|
Conrozier 1992 [33] RCT |
56 |
hpCS 3 × 400 mg/day PLB 6 months |
Pain (VAS); LI; analgesic consumption; patient’s assessment, hpCS better than PLB |
| Knee OA | |||
|
Uebelhart 1998 [34] RCT pilot |
42 |
hpCS 800 mg/day PLB 1 year |
Pain and overall mobility (VAS) at 3 (p < 0.05) and 12 (p < 0.01) months hpCS better than PLB |
|
Uebelhart 2004 [35] RCT |
120 |
hpCS 800 mg/day PLB 2 × 3 months during 1 year |
hpCS: more LI decrease (36% hpCS vs 23% PLB; p = 0.001); less JSW reduction (0.44 vs 0.46 mm p < 0.05) than PLB |
|
Michel 2005 [36] RCT |
300 |
hpCS 800 mg/day PLB 2 years |
JWS at 2 years: hpCS no change; PLB − 0.14 mm, (p < 0.001 vs. baseline) |
|
Radrigàn 2007 [37] Open, non-controlled |
61 |
hpCS 800 mg/day for 3 months follow-up: 6 months |
Improvement of 44.4% in the LI (p < 0.0001) and of 56.8% (right) and 61.7% (left) in the knee pain measured by VAS |
|
Kahan 2009 [38] RCT |
622 |
hpCS 800 mg/day PLB 2 years |
Reduction in JSW loss with hpCS (p < 0.0001 vs. PLB); less patients with radiographic progression in hpCS (p < 0.0005) |
|
Möller 2010 [39] RCT |
129 |
hpCS 800 mg/day PLB 3 months |
hpCS better than PLB in pain at VAS (p < 0.01), LI (p < 0.05) reduction of use of analgesics (p < 0.05) |
|
Wildi 2011 [40] RCT |
69 |
hpCS 800 mg/day PLB 6 months double- blind hpCS 800 mg/ day 6 months open-label |
Less cartilage volume loss in hpCS than in PLB group (p = 0.03). Lower subchondral BML scores in hpCS group at 12 months (lateral compartment p = 0.035; lateral condyle p = 0.044) |
|
Montfort 2012 [41] RCT |
45 |
hpCS 800 mg/day paracetamol 4000 mg/day 6 months |
hpCS significantly reduced synovitis compared to paracetamol (p < 0.01) hpCS effectively reduced functional incapacity (p < 0.01) |
|
Reginster 2017 [42] RCT |
604 |
hpCS 800 mg/day celecoxib 200 mg/day PLB 6 months |
At day 182 pain (VAS) reduced (p = 0.001 hpCS; p = 0.009 celecoxib) and LI reduced (p = 0.023 hpCS; p = 0.015 celecoxib) vs. PLB |
| Hand OA | |||
|
Wang 1992 [43] RCT |
34 |
hpCS 3 × 400/day PLB 18 months |
hpCS reduced pain (VAS) and improved hand function |
|
Verbruggen 1998 [44] RCT |
119 |
hpCS 3 × 400 mg/day PLB 3 years |
Patients with new joints with lesions: hpCS 5.9%; PLB 22.4% |
|
Rovetta 2002 [45] RCT |
24 |
hpCS 800 mg/day + naproxen 500 mg/day naproxen 500 mg/day 24 months |
hpCS + naproxen lower increase in number of joints with erosions (p < 0.05) |
|
Rovetta 2004 [46] RCT |
24 |
hpCS 800 mg/day + naproxen 500 mg/day naproxen 500 mg/day 24 months |
hpCS + naproxen better than naproxen in Heberden (p < 0.001) and Dreiser (p < 0.001) scores, in patient’s (p < 0.001) and clinician’s (p < 0.001) judgement |
|
Gabay 2011 [47] RCT |
162 |
hpCS 800 mg/day PLB 6 months |
Significant decrease in the patient’s global assessment of hand pain (difference VAS scores − 8.7 mm; p = 0.016) and significant improvement in FIHOA score (− 2.14; p = 0.008) in hpCS group vs placebo |
|
Condrosulf 1200 mg Knee OA |
|||
|
Morreale 1996 [48] RCT |
146 |
hpCS 3 × 400 mg/day diclofenac 3 × 50 mg/day; 3 months + 3 months follow-up |
LI hpCS − 64.4%; diclofenac vs − 29.7% vs baseline; paracetamol consumption hpCs − 88%; diclofenac − 37.8% (p < 0.01) |
|
Bourgeois 1998 [49] RCT |
127 |
hpCS gel 1 × 1200 mg/day hpCS 3 × 400 mg/day PLB 3 months |
hpCS 1 × 1200 and 3 × 400 lower than PLB in LI (p < 0.0001 at day 91) and pain (VAS) (hpCS 1 × 1200 p < 0.01 from day 14; hpCS 3 × 400 p < 0.005 from day 42) |
|
Pavelka 1998 [50] RCT |
140 |
hpCS 200 mg/die 2 × 400 mg/die 3 × 400 mg/die PLB 3 months |
hpCS 2 × 400 and 3 × 400 mg/die more effective than 200 mg/die and PLB on LI (p < 0.01); pain at VAS (p < 0.01). No difference between 2 × 400 and 3 × 400 mg/day |
|
Clegg 2006 [51] RCT |
1583 |
hpCS 3 × 400 mg/day GlcN 3 × 500 mg/day GlcN + hpCS celecoxib 200 mg/day PLB 2 years |
Response rate, percent difference from PLB GlcN + 3.9% (p = 0.30), hpCS: + 5.3% (p = 0.17), GlcN + hpCS: % 6.5% (p = 0.09) celecoxib: + 10.0% (p = 0.008) |
|
Zegels 2013 [52] RCT |
353 |
hpCS 1 × 1200 mg/day 3 × 400 mg/day PLB |
hpCS 1200 mg or hpCS 3 × 400 mg/day significantly improved compared to PLB in terms of LI (p < 0.001) and VAS for spontaneous pain (p < 0.01) |
|
Pelletier 2016 [53] RCT |
114 |
hpCS 3 × 400 mg/day celecoxib 200 mg/day 2 years |
hpCS showed less cartilage loss than celecoxib in medial compartment (p = 0.018) and medial condyle (p = 0.008) |
|
IBSA 2019 RCT |
246 |
hpCS 1 × 1200 mg/day hpCS 3 × 400 mg/day 91 days |
hpCS 1200 mg once daily not inferior to hpCS 3 × 400 mg/day in LI (− 2.9 ± 0.3; − 2.6 ± 0.3, respectively; p < 0.0001). No significant difference regarding pain, NSAIDs consumption |
|
IBSA 2019 RCT |
94 |
hpCS 1 × 1200 mg/day hpCS 3 × 400 mg/day PLB 91 days |
Mean (± SD) decrease of LI from baseline to day 91: − 4.3 (3.3) in the hpCS 1200 mg group, − 4.1 (2.9) in the hpCS 400 mg group and − 1.0 (2.0) in the PLB group |
| Pharmacoeconomy | |||
|
Bruyère 2009 [58] Knee OA RCT |
622 |
hpCS 800 mg/die PLB 2 years |
Health Utility Index better for hpCS than PLB at 6 months (p < 0.03) |
|
Lagnaoui 2006 [59] OA Prospective observational |
844 |
hpCS 800–1200 mg/day Long-term (≥ 3 months) Recent (< 3 months) users |
Lower consumption of NSAIDs (p < 0.05) and analgesics (p < 0.01) by long-term users |
|
Rubio-Terres 2010 [4] OA Observational retrospective |
530 |
CS NSAIDs CS + NSAIDs 6-months |
Treatment cost 6-month: CS €141; NSAIDs €182. Concomitant CS could reduce use of NSAIDs |