14 THERAPY

RheIll!ldnjd anilrm. - new approad1es

Combination therapies and early aggressive treat­ment may improve clinical outcomes for patients with rheumatoid anhritis (RA).I This is the opinion of Dr Fe Breedveld. of University Hospital, Leiden, The Netherlands, commenting on two studies that showed such benefits.

Cydo<porinplusmetbotrexate In a placebo-controlled. multicentre study involv­

ing 148 patients with RA in the US and Canada. cyclosporin was given in addition to patients' m.aximum tolerated dose of methotrexate.2 Patients received cyclosporin 1.25 mglkg bid. increased in increments of 0.5 mglkglday at weeks 2, 4, 8,12 and 16 until no joints remained actively innamed (maximum dosage 5 mglkglday). Combination therapy produced consistent, significant reductions in joint swelling. tenderness, pain and disability,2

The study authors note that cyclosporin and merhO(I'exate may be an effective combination because they act on different inflammatory pathways. No unacceptable toxic effects were observed.

-plus ••. In a study involving 128 patiems with early. active

RA at 13 centres in the UK. prednisolone 7.5 mg/day was added to other treatments currently being received.] Any accompanying treatment was allowed except those involving systemic corticosteroids. Radiological examination at 2 years showed a 'substantially' reduced rate of disease progression with prednisolone. compared with placebo.

Dr Breedveld suggests that the rapid progression of irreversible structural damage early in the course of RA calls for more aggressive early treatment of patients when nonsteroidal an!i~inflammatory agents fail. Oherwise, some patients will develop extensive. refractory disease that might have been avoided. says Dr Breedveld. He calls for long~tenn studies to discover prognostic markers that coold permit early identification of these patients. 1

1. Brw:lveld FC. New ponpcctivcs on treating rbeumar.oid e1britis. New

EnsJandJoumaI of Medicine 333: 18),184,20 Jull995 2. TupeD P, t;I: aI.

CombinaIiDu Ibo:rapy wilh cydospori..e and ~ in oe~crc rbeumaoid .-thrills. New EnglandJoumaI ofMedlciDc 333: 137· 141. 20 Jill 190M 3. Kirwan JR. eI aI. Tbc effCC'l of gll>COC1OIticoids on joint c1eswctioD ia rbcwnaIoid .nhrilis. New Engl.aQdlOW11a1 ofMedicix 333: 142- 146, 20 lull99S ...,,_ ,

Intra-articular somattNatin ba<; potential in RA

Intra~articular somatostatin appears to have both anti-inflammatory and analgesic effects in patients with rheumatoid arthritis (RA), say Italian researchers.

In their study, 41 patients with active RA received a total of 6 intra~articular injections of somatostatin 750Jlg administered at l5-day intervals. Patients continued to receive their usual regimens of disease~ modifying agents and NSAIDs, but not corticosteroids.

2OJuI1905 INPHARIM-

Mean scores for pain at rest and on movement were significantly reduced after the second injection. while joint tenderness and moming stiffness were signifi~ cantly improved after the third injection. Progressive improvement in each of these parameters was observed with each injection. Efficacy was considered to be good or excellent by 78% of patients, and all patients felt that tolerability was good or excellent.

The researchers believe that somatostatin may inhibit neurogenic inflammation by inhibiting the release of substance P. Somatostatin also appears to inhibit lymphocyte proliferation and monocyte chemotaxis. Fiorav:;mli A. GoVODi M. La MOIItagna G. ~ G. Tirri G, t;I: aI. Somal<»latin 14 and joint i.nflammatio>l: evidence fur iJltraarucuIar efficac)' of prolo!>g<;d administrUloD ia rheumatoid anhrilis.. OnIgs UDder E~tallDd CliIIic&I Reoearcto 21 : 97-103. No. 3. 1995 ...........

Phenytoin: a new treatment option forRA?

Phenytoin could be a useful addition to the therapeutic armamentarium for rheumatoid arthritis (RA), according to researchers at the Nizam Institute of Medical Sciences, India.

Patients with active RA were randomised to 6 months' treatment with phenytoin 200 mg/day (n "" 40), chloroquine 150 mg/day (32) or auranofin 6 mg/day (36) in a double-blind fashion. Significant improve~ ments in clinical and laboratory measures of disease activity were seen with all 3 treatments.

Although none of the drugs showed superiority when all patients were considered, analysis of patients with a 3~ to 6-month history of RA showed a significantly higher rate of global improvement with phenytoin treatment (16/17 patients) compared with chloroquine (12118) and auranofin (12118). Adverse events occurred with similar frequency in the 3 groups.

If long~term trials confinn these findings, phenytoin may become an economical alternative to oral gold therapy, conclude the researchers. RIO URIC. Naldu MlJR. Kumar TK, Sbobha U, A$kar MA. t;I: aI. Comparison of pbtD)'\Oia with aunmofin and chlaroquinc ia rbeumaioid anhriti. _ • double blind stlldy. Joumal otRllcumatology 22: 1235- ll4O. Jill 190M _ ,., ...

News in brief ••.

• Lysine clonixinate appears to be as effective as ibuprofen in treating pain associated with gonarthrosis, according to the results of a German study. 147 evaluable patients with painful gonarthrosis were randomised to receive oral lysine clonixinate 375-750 mg/day or ibuprofen 1200-2400 mg/day for 4 weeks. The mean intensity of knee pain during a11~day activity was reduced by 49% from baseline in the lysine c10ruxinate group and by 46% in the ibuprofen group. Tolerability was considered to be good or very good by 94% of lysine clonixinate recipients and 87% of ibuprofen recipients. Ebr:rhardl R. t;I: at. Analgesic efficacy md tolerability of Iy.iae-clollilin.l\e VCl"SUS ibuprofen ill paPents with golWthro$is. OimDt Tbtnpcutic Researcl! S6: 57),580, IUD I99S ....,.'"