NEW PHARMACOLOGICAL TREATMENT OF OSTEOARTHROSIS
Pain is the principle reason for which patients with osteoarthritis (OA) seek help. Current guidelines for treatment emphasise a stepwise pharmacological approach (1-4) but in practice a multi-faceted approach may be preferable. Established pharmacological approaches have been challenged and drugs with novel modes of action proposed. Whilst this talk focuses on pharmacological approaches increasing evidence is accruing for the validity of non-pharmacological treatments including exercise, education and various surgical techniques and these should not be underemphasized as part of comprehensive management (3). A new classification of OA drugs has been proposed. This acknowledges the route of administration (systemic, local, topical), onset of action (rapid, slow) and the possibility of disease modification. Available drugs achieve symptomatic relief but disease-modification remains unproven.
Non-steroidal anti-inflammatory drugs (NSAIDs) are the most widely used agents but their superiority to analgesics is questionable ; their adverse event profile, particularly gastric ulceration is unquestionable. Some evidence suggests that they may also affect the osteoarthritis process itself (5). Therefore acetaminophen should be first-line therapy for most patients with OA with NSAIDs reserved for non-responders (1-4). No NSAID appears more effective in treating OA (6,7). The development of COX-2 selective agents such as rofecoxib and celecoxib has the potential to reduce gastric adverse events (8,9) but their precise place with regards to other NSAIDs and acetaminophen remains debatable (10). The use of prophylactic agents with NSAIDs has been studied and on present data both misoprostol and proton pump inhibitors have their place but targeting this therapy remains problematic (4). Topical NSAIDs are more effective than placebo and in addition give the patient a degree of control of therapy that is desirable but their precise role in therapy remains hotly debated (4). Capsaicin is also effective in OA and similarly promotes self-efficacy (6). Local injection with anaesthetics and corticosteroids has a transient benefit and current data suggest that concerns regarding joint deterioration and sepsis have been over-estimated (11).
A variety of slow-acting symptomatic drugs have been subjected to randomised controlled trials and demonstrated to be effective. These may be administered systemically e. g. chondroitin sulphate (12), glucosamine sulphate (13), or locally e. g. hyaluronic acid preparations (6). The characteristic feature of such drugs is a slow onset of action but prolonged benefit. Cost and, in some cases, safety issues may be of concern (13). It has long been recognised that OA is a metabolically active process and hence susceptible to modification. Most work has centred on cartilage and this may be misplaced ; other tissues (e. g. bone, muscle and nerve) may be equally if not more important. It remains to be seen how much of a role structure/disease modification may have in the future.
Current treatment of OA, as with many common conditions is being re-evaluated. Novel agents are opening up new therapeutic avenues but their precise role in the armamentarium remains to be established.
References
1) Hochberg MC et al. Arthritis Rheum1995 ; 38 : 1535-40.
2) Hochberg MC et al. Arthritis Rheum1995 ; 38 : 1541-7.
3) Lane NE et al. Am J Med1997 ; 103(6A) : 25S-30S.
4) Eccles M et al. BMJ1998 ; 317 : 526-30.
5) Huskisson EC et al. J Rheumatol1995 ; 22 : 1941-6.
6) Towheed TE, Hochberg MC. Semin Arthritis Rheum 1997 ; 26 : 755-70.
7) Towheed T, Hochberg M. J Rheumatol1997 ; 24 : 349-57.
8) Laine et al. Gastroenterol1999 ; 117 : 776-83.
9) Langman MJ et al. JAMA1999 ; 282 : 1929-33.
10) Freemantle N. Rheumatol 2000 ; 232-4.
11) Creamer P. Curr Opin Rheumatol1999 ; 11 : 417-21.
12) Morreale P et al. J Rheumatol1996 ; 23 : 1385-91.
13) Adams ME. Lancet1999 ; 354 : 353-4.
EARLY REVIEW OF PATIENTS AWAITING TOTAL HIP OR KNEE REPLACEMENT SURGERY -INDICATIONS TO ALTER PRIORITY ON WAITING LIST.
Garry Lewis, Pain Clinic and Department of Anaesthesia, New England Regional Hospital, Armidale, NSW, 2350, Australia.
Aim of investigation:To establish an early joint assessment clinic for orthopaedic patients awaiting hip or knee arthroplasty in order to improve patient preparation and waiting list management and to compare our experience with a 1996 Scottish study.
Method:A multi-disciplinary team assessed 48 patients as soon as possible after their referral for surgery, frequently over a year prior to operation, optimised their physical status and home situation and changed their priority when indicated.
Results:91.7% of Australian patients presented with osteoarthritis compared with 50.5% of Scots and 4.1% of Australians and 42.25% of Scots (p < 0.0001) had rheumatoid arthritis. Most patients planned active pursuits post-operatively though 45 of 48 had co-morbidities and referrals to optimise treatment were made in 18 cases. The length of the waiting list, approximately 16 months for routine cases concerned 31.25%. Curtailment of a valued occupation was followed frequently by psychosocial deterioration and among those patients only having 0 -1 residual occupations psychosocial deterioration warranting urgent re-prioritisation occurred in 10 of 13 (p < 0.025) and soon another was prioritised as urgent. All those (6) with 2 or more residual valued occupations did not deteriorate psychosocially nor did any of them require a change in prioritisation (p < 0.05).
Conclusions:Early pre-operative assessment and review is worthwhile, being accepted throughout this health region as a permanent service, which is cost-neutral. At review 15 of 48 patients had their priority altered, most frequently from ‘routine’ to ‘urgent’ due to psychosocial deterioration considered secondary to forced curtailment of a valued occupation.
PAIN, DISABILITY AND ANALGESIA IN PATIENTS WAITING FOR TOTAL HEMI-ARTHROPLASTY.
Dr M Human, Dr P D Collins. The Pain Clinic Department, Taunton and Somerset Hospital, Taunton, Somerset, TA1 5 DA
Aim of investigation:many patients currently wait at least a year for total hip or knee arthroplasty in the UK. It is the supposition of the authors that analgesia during this time is sub-optimal.
Method:over a period of 4 months patients presenting for surgery were assessed for disability and pain using the Oxford Hip or Knee Score and the short form McGill questionnaire. In addition, all forms of analgesia prescribed were recorded and the corresponding patient compliance.
Results:preliminary analysis suggests that patients suffer a significant degree of pain prior to their surgery, yet analgesia prescription is variable, particularly with opiates.
Conclusions:the results of this audit will be presented to the regional Primary Care Group together with recommendations from the pain clinic. It is envisaged that this will provide positive educational information for the primary care workers who manage the majority of these pain patients.
3-MONTH EFFICACY AND SAFETY STUDY OF OXYCONTIN ® IN OSTEOARTHTRITIS PATIENTS.
E. McCroskery, J. Croft*, J. Markenson#, L. Haskell, U. Mullins and R. Reder *Arthritis Center, Chevy Chase, Maryland, 20815 #Hospital for Special Surgery, NY, NY 10021 Purdue Pharma L.P., Norwalk, Connecticut 06850
Aim:Pain due to Osteoarthritis (OA) is often associated with interference of daily function. OxyContin ® is a controlled-release dosage form of the mu-opioid agonist, oxycodone. This double-blind, randomized, placebo-controlled study in OA patients investigated whether OxyContin ® would provide significant reductions in pain intensities and interference with aspects of daily life, and also investigated the safety of a 3-month treatment period with OxyContin ® .
Method:Eligible patients with moderate to severe pain inadequately managed with NSAIDs or as-needed opioid therapy were randomized to oral Placebo or OxyContin ® every 12 hours, dosing titrated until pain level and dose were stable for 48 hours. Subjects were allowed to continue previous stable regimens of acetaminophen, NSAIDs or oral steroids. OxyContin ® dose adjustments were allowed throughout to control pain or side effects. Analyses were completed on the intent-to treat population.
Results:OxyContin ® demonstrated superior efficacy to Placebo on all dimensions of the Brief Pain Inventory (11-point and/or 100mm VAS scales) as follows:
Pain Intensity Scales (Baseline / Day 15 or Stable Dosing)
| Placebo | OxyContin | |
| Average | 6.3 / 6.0 | 6.9 / 5.1 * |
| Right Now | 6.1 / 5.8 | 6.2 / 4.8 * |
| Worst | 7.9 / 6.9 | 8.0 / 6.0* |
| Least | 4.9 / 4.6 | 5.0 / 3.7* |
| Relief Provided | 40.8 / 35.8 | 35.6 / 56.2* |
Pain Interference Scales (Baseline / Day 15 or Stable Dosing)
| Placebo | OxyContin | |
| Composite Score | 5.8 / 5.3 | 6.2 / 4.0* |
| Composite Physical | 6.4 / 6.1 | 6.8 / 4.8* |
| Mood | 5.7 / 5.0 | 5.9 / 3.8* |
| Normal Work | 6.5 / 6.2 | 6.9 / 5.2* |
| Sleep | 5.6 / 4.8 | 6.4 / 3.0* |
| Life Enjoyment | 6.2 / 5.3 | 6.5 / 4.1* |
[Least Square Mean, * = p < 0.05, significant from baseline and placebo].
Discontinuations due to lack of efficacy were 67% Placebo and 16% OxyContin ® , respectively. The observed side effects in Ћ10% of the subjects were constipation, nausea, dizziness, somnolence, headache and pruitus.
Conclusions:OxyContin significantly reduced pain and associated interference in daily function in OA patients and the safety profile over the 3-month study was typical of opioid analgesics.
DIAGNOSTICS AND REHABILITATION OF PATIENTS WITH SENSOPATHY AT SOMATIC EMERGENCY HOSPITAL.
Pavel P.Pyrkov
Aim of investigation:We analyzed sensopathy diagnostics features with patients of therapeutic and surgery departments, methods of their treatments and rehabilitation.
Methods:Clinical-society, clinical-laborathory, psycho-pathologycal.
Results:Studied were 286 patients aged from 26 to 49 years, 78,32% of which were female. 64,43%were diagnosed to suffer depression (endogenous - 27%, neurotic - 73%), 30,97% suffered hysteric neurosis, 4,6% had phobias caused by mental deficiency. Prior to hospitalization 39,16% of patients had been observed by psychiatrists. Treatment and rehabilitation were conducted both by psychiatrists and somatic physicians. Such a tandem was provided by round the clock psychiatric service organized at multipurpose somatic emergency hospital (1600 beds). Treatment included psychotherapy, psycho-pharmacotherapy, physiotherapy, hypnotherapy and mechanotherapy. Not a single patient was transferred to specialized psychiatric hospital. Further examination revealed that in two months only 5% of patients from time to time still had senestoalgia. All patients were admitted to be able to return to return to work.
Resume:Presence of round the clock psychiatric service in the framework of somatic emergency hospital allows to earlier diagnose sensopathy, to lighten the burden of somatic diagnostic, to rise efficiency and to provide favorable sosial rehabilitation
ACUTE PHASE REACTANTS IN RELATION TO SEROTONIN AND JOINT PAIN IN PATIENTS WITH RHEUMATOID ARTHRITIS
Sigvard Kopp, Per Alstergren, Dept Clinical Oral Physiology, Karolinska Institutet, Stockholm, Sweden.
Aim of investigation:To investigate the relationship between erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), serotonin (5-HT) and joint pain in patients with rheumatoid arthritis (RA).
Patients and Methods:Twenty-six patients with seropositive (RF+) and 24 with seronegative (RF-) RA were investigated for general joint and temporomandibular joint (TMJ) pain by a visual analogue scale as well as for tenderness to digital palpation (TDP) and pressure pain threshold (PPT) over the TMJ and on the glabella. Venous blood samples were taken for ESR, CRP and plasma/serum level of 5-HT (P-5-HT/S-5-HT). A TMJ synovial fluid sample was also taken and analyzed for 5-HT (SF-5-HT).
Results:The ESR, CRP and P-5-HT were all significantly higher in the RF+ than in the RF- group. In the RF+ group both ESR and CRP were correlated to general joint pain. ESR was also correlated to TDP, while CRP also was correlated to S-5-HT and SF-5-HT as well as PPT of the glabella. In the RF- group ESR was correlated to TDP and S-5-HT, while CRP was correlated to PPT of the glabella.
Conclusions:ESR and CRP seem to be associated with general joint pain and local allodynia/ hyperalgesia in RA/RF+ patients, but only with allodynia/ hyperalgesia in RA/RF- patients. CRP is associated with S-5-HT and SF-5-HT in RA/RF+ patients, while ESR is associated with S-5-HT in RA/RF- patients.
Acknowledgements:Supported by Karolinska Institutet and Swedish Dental Society.
Pain in Europe III. EFIC 2000, Nice, France, September 26-29, 2000. Abstracts book, p. 141, 244, 250-275.
