Remission-inducing Drugs Research Articles

Relationship between mucosal healing by tacrolimus and relapse of refractory ulcerative colitis: a retrospective study

BackgroundTacrolimus (TAC) is a powerful remission-inducing drug for refractory ulcerative colitis (UC). However, it is unclear whether mucosal healing (MH) influences relapse after completion of TAC.We investigated whether MH is related to relapse after TAC.Patients: Among 109 patients treated with TAC, 86 patients achieved clinical remission and 55 of them underwent colonoscopy at the end of TAC. These 55 patients were investigated.MethodsPatients with MH at the end of TAC were classified into the MH group (n = 41), while patients without MH were classified into the non-MH group (n = 14). These groups were compared with respect to 1) clinical characteristics before treatment, 2) clinical characteristics on completion of treatment, and 3) the relapse rate and adverse events rates. This is a retrospective study conducted at a single institution.Results1) There was a significant difference in baseline age between the two groups before TAC therapy, but there were no significant differences in other clinical characteristics. The NMH group was younger (MH group: 48.1 (23–79) years, NMH group: 36.3 (18–58) years, P = 0.007). Endoscopic scores showed significant differences between the 2 groups at the end of TAC. There were also significant differences in the steroid-free rate after 24 weeks (MH group: 85.3%, NMH group 50%, P = 0.012). There was no significant difference in the relapse rate between the 2 groups at 100 days after remission, but a significant difference was noted at 300 days (17% vs. 43%), 500 days (17% vs. 75%), and 1000 days (17% vs. 81%) (all P < 0.05).ConclusionsTAC is effective for refractory ulcerative colitis. However, even if clinical remission is achieved, relapse is frequent when colonoscopy shows that MH has not been achieved. It is important to evaluate the mucosal response by colonoscopy on completion of TAC.

A history of the term "DMARD".

The article outlines a history of the concept of “disease-modifying antirheumatic drugs” or DMARDs—from the emergence in the 1970s of the idea of drugs with decisive long-term effects on bone erosion in rheumatoid arthritis (RA), through the consolidation and popularisation in the term DMARD in 1980s and 1990s. It then examines the usage of the terms “remission-inducing drugs” (RIDs) and “slow-acting anti-rheumatic drugs” (SAARDs), which for some years offered competition to the term DMARDs, thus underscoring the contingency of the establishment of DMARD as a word. Finally, it juxtaposes the apparently spontaneous emergence of the three terms DMARD, SAARD and RID, and the disappearance of the latter two, with a failed attempt in the early 1990s to replace these terms with the new term “disease-controlling antirheumatic treatment” (DC-ART). The analysis highlights the paradoxical qualities of the DMARD concept as robust albeit tension ridden, while playing down the role of identified individuals and overarching explanations of purpose.

Thalidomide for the treatment of resistant cutaneous lupus: Efficacy and safety of different therapeutic regimens

Thalidomide is effective for the treatment of severe cutaneous lupus. Our aim was to study the safety and efficacy of different doses of thalidomide in this condition. We studied patients with severe cutaneous lupus that was unresponsive to antimalarials, prednisolone, methotrexate, azathioprine, and cyclosporin A. Starting doses of 100 mg daily (n = 16 patients), 50 mg daily (n = 17), or 50 mg on alternate days (n = 15) were compared. The response to thalidomide was categorized as complete remission, partial remission, or no visible improvement. All patients received a baseline electromyogram (EMG) followed by repeat EMG every 3 to 6 months, or sooner if neuropathic symptoms developed. Forty-eight patients (46 female; mean [+/- SD] age, 44 +/- 12 years; range, 22 to 71 years) with discoid lupus (n = 18), subacute cutaneous lupus (n = 6), or systemic lupus erythematosus with skin involvement (n = 24) were included. The response rate was 81%, including 29 patients (60%) in complete remission and 10 (21%) in partial remission. Nine patients (19%) failed to respond. Thirteen patients (27%) developed peripheral neuropathy, which was EMG-proven in 11, including 4 patients in the 50-mg alternate-day group. Other side effects included drowsiness, constipation or abdominal pain, and amenorrhea. The relapse rate after stopping thalidomide was 67% (26/39). There was no association between a positive response to the drug and either starting doses or cumulative dose. Similarly, no association was found between peripheral neuropathy and the starting or cumulative dose. Thalidomide is effective for the treatment of severe cutaneous lupus. There were no clear dose-dependent effects. However, the high incidence of neurotoxicity, even at low doses, suggests that it may be most useful as a remission-inducing drug.

Rational use of new and existing disease-modifying agents in rheumatoid arthritis.

Because of radiographic evidence of progressive bone loss and the inability to eliminate synovial proliferation with methotrexate, it became apparent that therapy for rheumatoid arthritis needed further advancement. Methotrexate is not a remission-inducing drug and may have dose-limiting toxicity. In the past 2 years, three new disease-modifying antirheumatic drugs (DMARDs) have been approved: leflunomide, etanercept, and infliximab. Each of these agents has demonstrated efficacy compared with placebo in randomized, controlled studies. Because methotrexate had a dominant therapeutic role, the new drugs were also studied in combination with it. Other established DMARDs, such as sulfasalazine and hydroxychloroquine, have also demonstrated efficacy when used together with methotrexate. The results of these combination studies clearly demonstrate that clinical responses can be meaningfully improved when new and existing DMARDs are added to methotrexate. Although toxicity remains a serious concern when powerful immune modulators and antimetabolites are used in combination, relatively few serious adverse events have been reported during 2-year treatment periods. It has also become apparent that combinations of new DMARDs and methotrexate virtually halt radiographic progression over 2 years. The new agents are expensive, but annual costs must be weighed against the personal and societal expense of joint arthroplasty, hospitalizations, disability, and diminished quality of life that accompanies poorly controlled rheumatoid arthritis. The ultimate value of combination DMARD therapy with methotrexate will be determined by long-term data on safety, efficacy, and effects on radiographic deterioration of bone. Additional long-term observational data on the incidence of joint arthroplasty and disability will help to place the issue of societal costs in a better perspective. This will allow the value of aggressive treatment to be established with certainty.

Analyse von Krankenkassendaten zur ambulanten Versorgung von Patienten mit chronischer Polyarthritis*

Ensuring the quality of the outpatient treatment of subjects suffering from rheumatoid arthritis requires an assessment of the treatment to 1) evaluate the present state of the treatment, 2) make suggestions towards optimisation and 3) evaluate the translation into reality of these suggestions for optimisation. The data of the (statutory) health insurance are a suitable basis for evaluation [L. von Ferber (ed.) 1994], since outpatient treatment can be analysed by means of person-related long-term observations encompassing all institutions even for illnesses that progress in phases (such as rheumatoid arthritis). Consulting an illness-specific, 45% random sample of all insured members with inflammatory joint diseases a prevalence of 0.44% (n = 268) was calculated for rheumatoid arthritis. A total prevalence of 0.06% was revealed for other rheumatic illnesses, such as ankylosing spondylitis (n = 27), psoriasis arthritis (n = 8) and Sjörgen's syndrome (n = 4). Considerable additional extra demand was found for the 307 patients suffering from rheumatic diseases: They visited approx. 1.5 times more different doctors and received 2.5 times as many medical services in comparison to a control group of "average" insured persons (matched pairs according to age and sex). The care of the rheumatic diseases was predominantly (224 of 307) patients in the hands of one specialist (mostly the GP). Referral to other specialists with a specific diagnosis of rheumatoid disease occurred only with one quarter of the patients. Only small differences in the spectrum of substance classes employed could be seen in drug therapy, according to the age of the patient or the medical discipline of the prescribing doctor. Analgesics are mainly prescribed on a short-term basis (one treatment quarter). However, so-called "basic therapeutics" (remission-inducing drugs) are employed only on a long-term basis (3 or 4 treatment quarters) in less than 50 per cent of the cases. Marked differences were found when comparing outpatient primary medical prescription data with those from specialised institutions (rheumatism centres, established rheumatologists): Basis therapeutics are employed less frequently and analgesics more frequently in outpatient treatment than in the special institutions. Non steroid antirheumatics are employed with a similar frequency (71 to 89%) in all institutions. A clear difference was also seen in the spectrum of the basic therapeutics employed depending on the prescribing institution. Analysis of treatment data by statutory health insurance shows that the rheumatoid arthritis patient has an outstanding access to the medical care system but that the quality of treatment cannot be considered sufficient. The differences seen in the comparison between the special institutions and the outpatient sector should give rise to critical discussion, and to carrying out further comparative analyses in the treatment research of patients suffering from rheumatic diseases.

Treatment of rheumatoid arthritis--does it affect society's cost for the disease?

To assess whether the treatment of rheumatoid arthritis reduces the cost to society of the disease, 62 patients were studied retrospectively over an 18 month period. The first 6 months (period 1) was the time before treatment with remission-inducing drugs (RID). The following 6 month period (period 2) was the time when RID treatment was started and suitable doses were evaluated. The last 6 month period (period 3) was the follow-up period when the results of the treatment were evaluated. The cost for drugs, surgical treatment, out-patient visits, blood tests and hospitalization days during periods 2 and 3 was calculated as 1.6 million SEK. During the same period, the cost for loss of productivity to society was reduced by 1.5 million SEK, assuming that the cost to society would have been unchanged, compared to period 1, if therapy had not been given. In a small group of patients who entered remission, the net saving for society exceeded the cost of treatment. The study indicates that the treatment of rheumatoid arthritis can lead to a reduced cost to society.

Assessment of antirheumatic activity in man

Although so-called disease-modifying antirheumatic drugs (DMARDs) have been trialled in a number of chronic arthropathies, including psoriatic arthritis, Reiter's syndrome and ankylosing spondylitis, it is their application in the treatment of rheumatoid arthritis (RA) that has attracted the greatest attention. The drugs of interest are slower in their onset of action than the non-steroidal anti-inflammatory drugs (NSAIDs) and appear to differ in the dimensionality of the response induced, producing less dramatic effects on pain and swelling but possibly having long-term advantage with respect to physical function and radiographic progression of disease. There has been much debate as to the correct terminology for this class of drugs, which in Canada includes the antimalarials, chloroquine and hydroxychloroquine, as well as sulphasalazine, sodium aurothiomalate, auranofin, D-penicillamine, methotrexate, azathioprine and cyclophosphamide. Other drugs in this group that have been tested but are not in routine use include levamisole and cyclosporin A. Some authors have favoured the term remission-inducing drugs (RIDS) or slow-acting remission-inducing drugs (SARIS), although others contend that, since a complete remission is rarely achieved, DMARDs is a better eponym. However, it is clear that compared to a placebo or no treatment, even NSAIDs modify the disease process. While it may be suggested that such a response leaves the long-term consequences of disease unaltered, it is hard to accept that the long-term outcome of RA is not improved in some way for those patients who demonstrate a substantial and sustained response in pain, swelling, stiffness, range of movement and activities of daily living to either a single trial or serial trials of several NSAIDs prescribed over time. Given the aforementioned problems, the term 'slow-acting antirheumatic drugs' or SAARDs is to be preferred (Currey, 1984). The majority of SAARDs appear at least in vitro to modulate the immune response, although some have received the specific designation of immunosuppressive or cytotoxic agents. It is because NSAIDs modify the symptoms of disease and SAARDs differ in their induction-response interval and may affect aspects of disease relatively untouched by NSAIDs that clinical trials of SAARDs differ in certain respects from those of NSAIDs. Furthermore, until recently, drugs such as methotrexate, azathioprine and cyclophosphamide were regarded as drugs

Clinical practice monitoring of slow-acting remission-inducing (SARI) drugs.

MONITORING OF SLOW-ACTING REMISSION-INDUCING (SARI) DRUGS Get access APRIL KAY APRIL KAY Arthritis and Rheumatism Council Epidemiology Research Unit, University of Manchester Address for correspondence: New Mill Cottage, Pewsey, Wiltshire SN9 5LD Search for other works by this author on: Oxford Academic PubMed Google Scholar Rheumatology, Volume 28, Issue 3, June 1989, Pages 239–241, https://doi.org/10.1093/rheumatology/28.3.239 Published: 01 June 1989

Treatment of psoriatic arthritis with sulphasalazine: A one year open study

Sulphasalazine (SASP) has recently become established as an effective treatment for active rheumatoid arthritis (RA), but has not previously been used in psoriatic arthritis in which remission-inducing drugs have proved disappointing. In this one year open study, 34 patients with active psoriatic arthritis were treated with sulphasalazine. An overall favourable clinical response was observed in 23 patients (67%). Nine patients (26%) achieved a very good therapeutic response and these either had arthritis associated with spondylitis or the symmetrical type of joint disease. Evaluation at 3, 6 and 12 months showed a significant improvement in inflammatory indices including a reduction in the C-reactive protein level and ESR. The drug was well-tolerated and side-effects were mild. Eight patients (23.5%) stopped the drug because of reactions and one patient with a rash was successfully desensitised. Fifty-three percent continued the drug into the second year. No apparent exacerbation of the psoriasis was observed. These results suggest that sulphasalazine is a safe and potentially effective drug in the treatment of psoriatic arthritis. A double-blind placebo-controlled trial has been set up to determine its true efficacy.

Auranofin in rheumatoid arthritis: use in patients with side-effects or lack of effect to gold sodium thiomalate or gold thioglucose and/or D-penicillamine. A prospective one year investigation.

Auranofin is a gold compound (triethylfosfine-gold) for peroral use which in clinical trials in patients with rheumatoid arthritis (RA) has been found superior to placebo (1-3) and comparable with parenterally injected gold salts (gold sodium thiomalate (GST) (Myocri-sin®) (3-6) or gold thioglucose (GT) (Sanocrysin®) and with orally administered D-penicillamine (D-pen) (7-10). Auranofin seems appropriate as an early alternative remission inducing drug (RID) in patients with active RA, since less severe side-effects have been reported. Although the pathophysiological action of auranofin is thought to be different from that of GST and GT it has been hypothesized that side-effects induced during GST and GT treatment may reappear during later gold therapy using auranofin. It is likewise an open question whether patients with active RA and a history of side-effects to or no effect of D-pen have an increased risk to develop auranofin side-effects. These questions have obvious clinical implications, since aurano...

慢性関節リウマチ治療におけるサルファサラジンの有用性 他の経口寛解導入薬との比較試験

We studied on effectiveness of sulphasalazine (SASP) in rheumatoid arthritis. SASP was compared with other oral remission-inducing drugs, D-penicillamine (D-P), auranofin (Aur), robenzarit (CCA) and methotrexate (MTX), for 6 months. In addition, we studied on cessation of treatment of each drug.After treatment of 6 months effectiveness of SASP turned out to be just the same with that of D-P and Aur. As for frequency of treatment cessation during 6 months MTX was the lowest among other drugs, being followed by D-P, SASP, Aur and CCA in order. As for achievement of continual administration of drug in each month MTX, D-P and SASP were significantly greater than Aur and CCA. The cessation of treatment due to side effect was more frequently seen in MTX and D-P. On the other hand in Aur and CCA the cessation of treatment was almost due to ineffectiveness.Many serious side effects were experienced in MTX and D-P, but not in SASP, Aur and CCA.In conclusion sulphasalazine turned out to be effective drug and tolerable over long periods in rheumatoid arthritis.

BASELINE AND INTERFERON‐ENHANCED NATURAL KILLER CELL ACTIVITY IN RHEUMATOID ARTHRITIS

Natural killer (NK) cell activity against the leukemia cell line K-562 was tested in 45 patients with rheumatoid arthritis (RA) who either had not received any remission-inducing drugs for more than 6 months or had received penicillamine for at least 6 months. Baseline NK cell activity and interferon (IF)-enhanced NK cell activity did not differ from that observed in 45 controls matched for age and sex, and neither NSAID (non steroidal anti-inflammatory drugs) nor penicillamine influenced NK cell activity. There was no correlation between NK cell activity and acute-phase reactants.

Modern management of rheumatoid arthritis

The management of rheumatoid arthritis can be challenging even to the most experienced and astute physician. The rheumatoid inflammatory process can be profound, ravaging, and unremitting, and the illness is notorious for its protean manifestations and capricious course. Moreover, the response to therapy is unpredictable, although it can be quite successful in many cases. Nevertheless, the intense pain, profound disability, progressive destructive arthropathy, and negative psychological milieu that haunt patients demand that something be done therapeutically. Rheumatoid arthritis responds best to a symphony of therapeutic modalities including drugs, rehabilitation, joint surgery, and attention to psychosocial issues. The foundation of any successful therapeutic venture is an educational program designed, however simply, to imbue the patient and family with an understanding of the disease and its course and treatment, and with realistic expectations. Drug therapy is often polypharmaceutical, employing analgesics, nonsteroidal anti-inflammatory agents, both local and systemic corticosteroids, and remission-inducing drugs. Pacing of lifestyle, physical and/or occupational therapy, vocational guidance, psychological and sexual counseling, and social intervention are as much a part of modern management in rheumatoid arthritis as are drugs. The extra-articular (systemic) manifestations are addressed in a variety of ways depending upon the type and severity of involvement. Although most patients can be treated by their primary care physician, some may require the expertise provided by a specialist. Finally, despite the lack of a cure for rheumatoid arthritis, most patients respond well to treatment and return to their desired activities of daily living.

Auranofin: Bane or bonanza for the nonrheumatologist

The availability of an oral gold preparation in the treatment of rheumatoid arthritis, with a claim to being effective yet safer than parenteral gold, will most certainly attract the attention of physicians and patients who previously would not have used chrysotherapy. Cardinal clinical features that may be especially helpful to the nonrheumatologist in the diagnosis of rheumatoid arthritis are outlined. The often unpredictable course of rheumatoid arthritis is stressed, emphasizing the need for an adequate trial of nonsteroidal anti-inflammatory drug therapy before instituting the use of a potentially more toxic remission-inducing drug such as gold. The absence of an immediate flare of synovitis, should the use of oral gold be sporadic, will aggravate the problem of patient noncompliance. Techniques to minimize this problem will be noted. Perseverence and careful record keeping by physicians not necessarily comfortable with the long-term management of chronic disease must be part of the therapeutic program.

Remission-inducing therapy in rheumatoid arthritis

Rheumatoid arthritis is characterized by immunologically mediated chronic inflammation of synovial structures. Remission-inducing drugs, such as gold compounds, antimalariais, and D-peniciliamine, have been shown to suppress disease activity in rheumatoid arthritis while having minimal nonspecific anti-inflammatory properties. The possibility that these agents are effective because they modulate the underlying immunologic reactivity prompted an examination of the immunosuppressive properties of these drugs. The evidence indicates that immunosuppression is an action that is shared by these agents and thus supports the view that remission induction may result from suppression of the immunologic activity that underlies rheumatoid inflammation. Despite the fact that these agents can function as immunosuppressives, each appears to have a unique site of action, specifically inhibiting the function of only one of the populations of cells likely to be involved in chronic immunologically mediated inflammation. Gold compounds and antimalariais appear to be active by virtue of their capacity to depress various functions of mononuclear phagocytes, while D-peniciliamine acts by inhibiting a number of the activities of T lymphocytes. These results imply that the means by which these drugs suppress rheumatoid inflammation are fundamentally different. This suggests the conclusion that the remission-inducing drugs may be classified as T cell-active and mononuclear phagocyte-active agents. A better understanding of the pathophysiology of rheumatoid arthritis should thus be helpful in deciding which of these classes of drugs is appropriate in individual cases.

Evaluation of pathophysiology and drug effects on rheumatoid arthritis

The treatment of rheumatoid arthritis has been divided into symptomatic or anti-inflammatory drug therapy, and disease-modifying or remission-inducing drug therapy. A more useful classification may be one that correlates the therapy with the component of the disease process that it affects. In general, nonsteroldal drugs do not affect cells as much as they do some of the mediators that cells produce. The effects of gold and D-penicillamine, although used later in the disease because of their toxicity, probably act early in the cascade of development of the disease by affecting the macrophages and lymphocytes. Prednisone may be effective in inhibiting synthesis by macrophages and fibroblasts of proteinases as well as arachidonic acid metabolites. Retinoids may be prototypes of drugs that selectively inhibit collagenase/proteinase production but do not affect production of normal connective tissue components.

Clinical synovitis and radiological lesions in rheumatoid arthritis. A prospective study of 25 patients during treatment with remission-inducing drugs.

The joints of hands and feet of 25 patients (1150 joints) with rheumatoid arthritis were compared, joint by joint, clinically and radiologically, over 2 years of treatment with remission-inducing drugs. Joints with clinical signs of synovitis decreased from 47% to 17% (p less than 0.001), while the number of joints with radiological lesions increased from 23% to 27% (p less than 0.01). Definite radiological progression of bone lesions was seen in 7% of the joints. Joints with clinical synovitis had a higher risk of progressive bone damage than joints without clinical synovitis (p less than 0.001) and joints in which the clinical signs of synovitis persisted during the study had a higher risk of progressing bone lesions than joints in which the clinical synovitis subsided (p less than 0.001). Progressive bone damage was seen more often in swollen joints than in tender joints without swelling or joints without clinical signs of synovitis (p less than 0.001), the difference in radiological progression between the latter two groups being non-significant. Twenty-one per cent of the joints with progressive bone lesions had no clinical signs of synovitis during the period.

Heroic Treatment for Nonmalignant Disease

Severe progressive rheumatoid arthritis remains a therapeutic challenge. The usual approach has been described by Wilbur Blechman as resembling choices from a Cantonese restaurant menu—take one or more from column A and also from column B. Thus, the control of inflammation, or at least of the symptoms produced by inflammation, is made a responsibility of nonsteroidal antiinflammatory drugs and, in some cases, of corticosteroids. At the same time, inhibition of the progression of the disease generally requires addition of disease-modifying antirheumatic drugs, also known as remission-inducing drugs, such as gold salts, penicillamine, antimalarials, azathioprine, and a variety of experimental drugs and procedures borrowed from the treatment of other diseases. Gold compounds were first introduced because of a confusion between tuberculosis and rheumatoid arthritis; penicillamine began as an agent to remove copper from patients who had Wilson's disease; chloroquine and hydroxychloroquine sulfate were used to prevent or treat malaria, while azathioprine

New Directions in Arthritis Therapy

Intended for primary care physicians, this book is a commentary on the drugs available for treating arthritis, with emphasis on the non-steroidal anti-inflammatory drugs and remission-inducing drugs. Therapy relates mainly to the treatment of rheumatoid disease (rheumatoid arthritis). The author has collected data at the Phoenix Arthritis Clinic in cooperation with various university medical centers for the American Rheumatism Association Medical Information System (ARAMIS). These postmarketing data provide useful information. Although limited at present, it is encouraging to have development of data that should more truly reflect patients' responses in a natural setting. The use of a patient prototype, Alice F., throughout the text and comments in the epilogue provide glimpses at Dr Roth's personal approach to handling rheumatoid disease. The appendix gives some useful tables, examples of the ARAMIS data base, and comparisons of data derived from ARAMIS. The use of Edward Takesue's groupings of non-steroidal anti-inflammatory drugs eases

Concanavalin A-induced suppressor cell activity and in vitro immunoglobulin secretion in rheumatoid arthritis: correlation with clinical and immunological parameters.

Concanavalin A-induced suppressor cell activity was found moderately but significantly (P less than 0.05) decreased in RA patients treated with nonsteroidal antiinflammatory drugs (31 +/- 7% suppression) as compared to patients on remission-inducing drugs, such as gold, penicillamine, or chloroquine (51 +/- 6%) or to healthy individuals (50 +/- 6%). Also, lymphocytes from patients with antibodies to collagen mediated lower suppression (33 +/- 7%) than lymphocytes from patients without evidence for these autoantibodies (61 +/- 11%). No significant difference between patients and controls or between individual groups of patients were observed in regard to IgM and IgG secretion induced by pokeweed mitogen. Thus, although no indication for a severe derangement of regulatory cells in peripheral blood of RA patients could be observed in this study, a slight deficiency of ConA-inducible suppressor cells that may be reverted by remission-inducing drugs seems to be present in RA.