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About Solatumfarma

Solatumfarma is a medical device company marketing a niche portfolio of high-quality products across everyday therapy and treatment areas. We currently have successful product solutions in urology, ophthalmology, orthopaedics and wound management and we are continuously evaluating new products that bring new value to an existing treatment area.

Our management team has long-standing experience in national and multi-national pharmaceuticals across a wide range of therapy areas. They have particular expertise in sourcing high-quality products across multiple markets, including market access and pricing, distribution and maintaining a consistent and reliable product supply.

This is played out through the ethos of our company where our vision is to market high-quality, proven healthcare products that enhance the management of everyday conditions – clinically, practically and economically.

The Solatumfarma name is derived from the Latin, Solatium, meaning comfort, which also inspires our core commitments. These are:

  • Solutions to needs that enhance patient comfort
  • A reliable supply of everyday products
  • Proven formulations with clinical benefit
  • Consistent high-quality, competitively priced

Do intra-articular hyaluronic acid injections delay total knee replacement in patients with osteoarthritis

Nearly one in five people over 45 years old have sought treatment for knee osteoarthritis (OA) and 98% of initial knee replacements are due to OA (Arthritis Research UK, 2013). Due to the growing prevalence of knee OA and the medical costs associated with total knee replacement (TKR), there is increasing interest in the search for minimally invasive treatments that can delay OA progression. Intra-articular hyaluronic acid (IA-HA) injections is one such treatment that is frequently used. However, the available literature is varied about the effectiveness of IA-HA injections.

A retrospective and observational study conducted in France between 2006 and 2013 by Delbarre et al. sought to compare the delay from diagnosis of knee OA to TKR between patients who received IA-HA and those who did not (Delbarre, et al., 2017).

Methods and patient selection

Patients were selected from two medico-administrative databases which could be linked together using a common patient identifier. From these databases, information on a patient’s ambulatory care, including IA injections, and date of TKR could be determined and the association explored.

The databases do not contain lab test or X-ray results and therefore, an algorithm was established to determine which patients were likely to have knee OA. The inclusion criteria were as follows (Fig 1):

  • At least one X-ray or arthroscopy of the knee followed by an IA injection (corticosteroid (CS) or HA) within 12 months
  • Aged 50 or over at the time of the X-ray or arthroscopy
  • The injection was prescribed by a rheumatologist, an orthopaedic surgeon, physician specialising in physical medicine and rehabilitation or a GP

The date of the X-ray or arthroscopy was used as a proxy to date the diagnosis of knee OA.

Adjustment variables that were considered included socio-demographics, general health and knee OA conditions, such as initial prescriber’s speciality, mean annual number of visits to specialist physicians, and number of knees with OA.

Based on these criteria, the study population consisted of 14,782 patients, of which 5306 had CS injections only (non-HA group) and 9476 had at least one HA injection (HA group) during the follow-up period. 1662 patients had TKR before the end of the study (31st December 2013).

Fig 1. Flow-chart of patients’ selection. IA: intra-articular, HA: hyaluronic acid, CS: corticosteroids, TKR: total knee replacement. HA group: patients who received at least one IA HA injection during their follow-up period, N-HA group: patients who received only CS as IA injections. The four specialists are rheumatologist, orthopaedic surgeon, physical medicine and rehabilitation practitioner and general practitioner.

Results

The bivariate analysis performed on the patients who had TKR shows that the mean time from diagnosis to TKR was significantly higher in the HA group than the non-HA group (Fig 2).

Everything else being equal, the restricted mean survival time from diagnosis of knee OA to TKR was 842 days for the HA-group and 625 days for the non-HA group (95% CI for both groups).

At each time point, the mean time without TKR was significantly higher in the HA group – from +57 days at 1 year and +217 days at 7.5 years after diagnosis.

These findings support the effectiveness of intra-articular hyaluronic acid injections in delaying total knee replacement.

A retrospective longitudinal study involving knee osteoarthritis patients

Fig 2. Kaplan-Meier curves of time without TKR for HA and non-HA groups. HA group: patients who received at least one IA HA injection during their follow-up period, non-HA group: patients who received only CS as IA injections, TKR: total knee replacement, IA: intra-articular, HA: hyaluronic acid, CS: corticosteroids.

References

  1. Arthritis Research UK, 2013. Osteoarthritis in general practice. [Online] [Accessed 15 August 2019].
  2. Delbarre, A. et al., 2017. Do intra-articular hyaluronic acid injections delay total knee replacement in patients with osteoarthritis – A Cox model analysis. PLoS One, 11(12), p. e0187227.

Hyaluronan treatment of interstitial cystitis/painful bladder syndrome

Interstitial cystitis, also known as painful bladder syndrome or IC/PBS, is a chronic inflammatory disease of the bladder causing long-term pelvic pain, urinary frequency and urgency. It can have a significant impact on lifestyle, work, relationships and emotional health 1

One of the leading hypotheses for the cause of IC/PBS is based on a urine-tissue barrier disorder – an imbalance in the protective lining of the bladder (the urothelium) causing permeation of toxic urinary compounds into the bladder wall, inducing urgency, frequency and pain 2. Glycosaminoglycans (GAGs) play an important role in the structure of the urothelium by reinforcing the surface and reducing direct contact with urine. Consequently, GAGs are involved in the pathophysiology, diagnosis and treatment for IC/PBS.

GAG replacement therapy is widely used to treat or manage IC/PBS – with considerable response rates. However, controlled studies on IC/PBS treatment are rare and often heterogeneous due to difficult diagnostic criteria, multifactorial aetiology and poorly-defined pathogenesis. In 2008, Riedl et al. conducted a study to evaluate the efficacy of intravesical therapeutic hyaluronic acid (hyaluronan) – a natural constituent of the GAG layer – in IC/PBS 2

Patient selection and method

Patients were included in this study if:

  • They had a positive modified potassium test to confirm they had a urine-tissue barrier disorder – i.e. they showed a >30% reduction in maximal bladder capacity 2
  • They were able to retain the instillations for a minimum of 2h 

Since 2000, 121 female patients with a diagnosis of IC/PBS were treated with weekly instillations of 50cm3phosphate-buffered saline solution containing 40mg hyaluronate. This means that patients with a very low functional capacity (<50cm3) were not candidates in this study.

Instillations were continued until patients were free of IC/PBS symptoms or they had significantly improved. If up to 10 instillations had been performed with no improvement, then treatment was stopped. 

Symptoms were recorded using a questionnaire to assess global-bladder or IC-related symptoms. The questionnaire used a visual analogue scale (VAS) rating from 0 (no symptoms) to 10 (maximal symptoms). Data was collected before initiation of therapy (pre-treatment) and again at a mean of 6.5 months after their last instillation. The post-treatment questionnaire asked patients about their symptoms at the time of their last instillation and at time of completion of the questionnaire. It also asked about overall impact of the therapy on their quality of life and if they would have it again.

Results

A positive and long-lasting impact of hyaluronan therapy on IC/PBS symptoms was evident in the assessment of pre-treatment and post-treatment VAS scores (see table 1). Pre-treatment VAS scores had a mean of 8.5, indicating severe symptoms. Post treatment, the mean VAS score was 3.5 showing a significant decrease (p<0.0001). At time of completion of the questionnaire, the VAS score remained stable at an average of 3.5 showing a long-term benefits of the treatment regimen.

Other key findings include:

  • 85% of patients reported an improvement of more than or equal to 2 VAS units following instillation therapy 
  • 15% reported a VAS score as 0 at the end of instillation therapy
  • 55% remained with no or minimal bladder symptoms after treatment
  • 84% reported that their quality of life had improved significantly
  • 86% would repeat hyaluronan instillations in the future if needed

Conclusions

In patients who discontinued the instillation regimen because their symptoms had significantly improved or disappeared, only 34.5% had to be reinstituted to maintain the therapeutic effect. Of note, patients in this study were treatment-naïve, having not received IC/PBS-specific therapy before. It may therefore be hypothesised that early GAG substitution can restore the urothelial or GAG defect. 

It is also interesting to note that the patients in this study all had a functional capacity of at least 50cm3, therefore excluding those with a low capacity. Given the results of this study and empirical data 2showing the potential of intravesical therapy, further research into instillation volume and dosing regimens aimed at these patients should be considered. The formulation of Solatum GAG replenisher as a standard 40mg dose in a lower 20cm3(20ml) volume makes it suitable for instillation and a potential treatment for those with a low functional capacity. 

Table 1. VAS symptom scores

PARAMETERHYALURONAN-TREATED PATIENTS (n=121)
VAS scores (mean ± SD (minimum−maximum)) 
Pre-treatment8.5 ± 1.7 (4.0−10.0)
Post treatment3.5 ± 2.7 (0.0−10.0)
Follow-upa3.5 ± 2.7 (0.0−10.0)
Mean VAS score changes (mean ± SD (minimum−maximum)) 
Pre-treatment to posttreatment −5.0 ± 2.8b(−10.0−0.0)
Posttreatment to follow-up+0.0 ± 2.3
Pre-treatment to follow-up−5 ± 2.9 (−10.0−1.0)
Patient changes between pre-treatment and follow-up 
Improved ≥2 VAS units103 (85%)
Improved <2 VAS units6 (5%)
Unchanged12 (10%)

VASVisual analogue scale, SDstandard deviation 

aFollow-up assessment refers to the VAS score recorded at the time of completion of the questionnaire 

bPre-treatment VAS score was significantly different (p<0.0001) from post treatment and follow-up scores; scores between posttreatment and follow-up were not significantly different (p=0.7036)

References

  1. NHS, “Interstitial cystitis,” 2018. [Online]. Available: https://www.nhs.uk/conditions/interstitial-cystitis/. [Accessed 20 August 2019].
  2. C. R. Riedl, P. F. Engelhardt and K. L. Daha, “Hyaluronan treatment of interstitial cystitis/painful bladder syndrome,” International Urogynecology Journal, no. 19, pp. 717-721, 2008.
  3. L. K. Daha, C. R. Riedl, G. Hohlbrugger, M. Knoll, P. F. Engelhardt and H. Pflüger, “Comparative Assessment of Maximal Bladder Capacity, 0.9% NaCl Versus 0.2 M Kcl, for the Diagnosis of Interstitial Cystitis: A Prospective Controlled Study,” The Journal of Urology, vol. 170, no. 3, pp. 807-809, 2003.
  4. G. Karsenty, W. AlTaweel, S. Hajebrahimi and J. Corcos, “Efficacy of Interstitial Cystitis Treatments: A Review,” European Association of Urology, vol. 4, pp. 47-61, 2006.